Wolbachia transinfections in Culex quinquefasciatus generate cytoplasmic incompatibility.

Culex quinquefasciatus is an important mosquito vector of a number of viral and protozoan pathogens of humans and animals, and naturally carries the endosymbiont Wolbachia pipientis, strain wPip. Wolbachia are used in two distinct vector control strategies: firstly, population suppression caused by mating incompatibilities between mass-released transinfected males and wild females; and secondly, the spread of pathogen transmission-blocking strains through populations. Using embryonic microinjection, two novel Wolbachia transinfections were generated in C. quinquefasciatus using strains native to the mosquito Aedes albopictus: a wAlbB single infection, and a wPip plus wAlbA superinfection. The wAlbB infection showed full bidirectional cytoplasmic incompatibility (CI) with wild-type C. quinquefasciatus in reciprocal crosses. The wPipwAlbA superinfection showed complete unidirectional CI, and therefore population invasion potential. Whereas the wAlbB strain showed comparatively low overall densities, similar to the native wPip, the wPipwAlbA superinfection reached over 400-fold higher densities in the salivary glands compared to the native wPip, suggesting it may be a candidate for pathogen transmission blocking.

Wolbachia strain wAlbA blocks Zika virus transmission in Aedes aegypti.

Transinfections of the maternally transmitted endosymbiont Wolbachia pipientis can reduce RNA virus replication and prevent transmission by Aedes aegypti, and also have the capacity to invade wild-type populations, potentially reaching and maintaining high infection frequencies. Levels of virus transmission blocking are positively correlated with Wolbachia intracellular density. Despite reaching high densities in Ae. aegypti, transinfections of wAlbA, a strain native to Aedes albopictus, showed no blocking of Semliki Forest Virus in previous intrathoracic injection challenges. To further characterize wAlbA blocking in Ae. aegypti, adult females were intrathoracically challenged with Zika (ZIKV) and dengue viruses, and then fed a ZIKV-containing bloodmeal. No blocking was observed with either virus when challenged by intrathoracic injection. However, when ZIKV was delivered orally, wAlbA-infected females showed a significant reduction in viral replication and dissemination compared with uninfected controls, as well as a complete absence of virus in saliva. Although other Wolbachia strains have been shown to cause more robust viral blocking in Ae. aegypti, these findings demonstrate that, in principle, wAlbA could be used to reduce virus transmission in this species. Moreover, the results highlight the potential for underestimation of the strength of virus-blocking when based on intrathoracic injection compared with more natural oral challenges.

Aqueously altered igneous rocks sampled on the floor of Jezero crater, Mars.

The Perseverance rover landed in Jezero crater, Mars, to investigate ancient lake and river deposits. We report observations of the crater floor, below the crater's sedimentary delta, finding that the floor consists of igneous rocks altered by water. The lowest exposed unit, informally named Séítah, is a coarsely crystalline olivine-rich rock, which accumulated at the base of a magma body. Magnesium-iron carbonates along grain boundaries indicate reactions with carbon dioxide-rich water under water-poor conditions. Overlying Séítah is a unit informally named Máaz, which we interpret as lava flows or the chemical complement to Séítah in a layered igneous body. Voids in these rocks contain sulfates and perchlorates, likely introduced by later near-surface brine evaporation. Core samples of these rocks have been stored aboard Perseverance for potential return to Earth.

An olivine cumulate outcrop on the floor of Jezero crater, Mars.

The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigated the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We found that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multistage cooling of a thick magma body.

A systematic review of interventions to reduce hospitalisation in Parkinson's disease.

UNLABELLED: The neurodegenerative process in Parkinson's disease (PD) results in a relentless progression of motor and non-motor symptoms. Affected individuals are frequently hospitalised for complications of the disease including falls, fractures, infections, and neuropsychiatric symptoms. When admitted to hospital, inpatient care is often suboptimal as it focusses on the primary cause of admission, and is associated with poor patient outcomes and significant healthcare costs. AIM: To review existing literature for evidence-based interventions aimed at reducing hospital admissions in PD. METHODS: Electronic literature search in EMBASE, MEDLINE and CINAHL databases for studies evaluating interventions to reduce hospital admissions in PD. We included publications with full abstracts, published in the English language and addressing interventions to reduce hospital admissions in PD. RESULTS: To date there are no randomised controlled trials addressing the topic. We identified nine relevant retrospective studies. Results from these studies suggest an association between frequent neurologist consultations, open access clinics, and medication compliance with a reduction in PD hospital admissions and emergency room visits. CONCLUSION: This systematic review highlights the lack of robust evidence for measures aimed at reducing hospital admissions in people with PD. Future prospective studies are required to evaluate the effectiveness of proposed interventions.

Effect of heparin and a low-molecular weight heparinoid on PAF-induced airway responses in neonatally immunized rabbits.

1. We have investigated the effect of an unfractionated heparin preparation, a low-molecular weight heparinoid (Org 10172) and the polyanionic molecule polyglutamic acid against PAF-induced airway hyperresponsiveness and pulmonary cell infiltration in neonatally immunized rabbits in vivo. 2. Exposure of neonatally immunized rabbits to aerosolized platelet activating factor (PAF) (80 micrograms ml-1 for 60 min) elicited an increase in airway responsiveness to inhaled histamine 24 h and 72 h following challenge which was associated with an infiltration of inflammatory cells into the airways, as assessed by bronchoalveolar lavage (BAL). 3. A significant increase in the total numbers of cells recovered from BAL fluid was associated with significantly increased cell numbers of neutrophils, eosinophils and mononuclear cells 24 h following PAF exposure. The numbers of eosinophils and neutrophils in the airways remained elevated 72 h after challenge. 4. The intravenous administration of an unfractionated preparation of heparin (100 units kg-1) or Org 10172 (100 micrograms kg-1) 30 min prior to PAF exposure significantly inhibited the airway hyperresponsiveness induced by PAF, 24 h and 72 h following challenge. PAF-induced hyperresponsiveness was not significantly affected by prior intravenous administration of polyglutamic acid (100 micrograms kg-1). 5. The intravenous administration of unfractionated heparin (100 units kg-1), Org 10172 (100 micrograms kg-1) or polyglutamic acid (100 micrograms kg-1) 30 min prior to PAF exposure significantly inhibited the expected increase in total cell infiltration. 6. This study shows that unfractionated heparin and a low-molecular weight heparinoid, Org 10172, are capable of inhibiting both the airway hyperresponsiveness and pulmonary cell infiltration induced by PAF in the rabbit.

Effect of a 5-lipoxygenase inhibitor and leukotriene antagonist (PF 5901) on PAF-induced airway responses in neonatally immunized rabbits.

1. Aerosol administration of platelet activating factor (PAF) (80 micrograms ml-1 for 60 min) to neonatally immunized rabbits caused bronchoconstriction which was far in excess of that produced by a comparable aerosol of bovine serum albumin (BSA), the carrier molecule for PAF. Bronchoconstriction of a similar magnitude was elicited by PAF in immunized, sham-immunized and normal rabbits. 2. Aerosol administration of PAF to immunized rabbits induced enhanced airway responsiveness to inhaled histamine in all animals tested, 24 h and 72 h after exposure. In not all cases had airways responsiveness returned to basal levels at 1 week following PAF challenge. In contrast, following exposure of immunized rabbits to BSA, no significant changes in airway responsiveness to histamine were evident at any of the measured time points. 3. A significant increase in the total number of inflammatory cells recovered in bronchoalveolar lavage (BAL) fluid was determined 24 h and 72 h following PAF exposure in immunized rabbits. This was associated with a significant increase in the number of neutrophils and eosinophils. Similar changes were observed following exposure of PAF to normal and sham-immunized rabbits. No change in the total number of inflammatory cells was obtained in BAL after BSA challenge to immunized rabbits; however, neutrophil numbers were significantly increased. 4. PF 5901, a specific inhibitor of the 5-lipoxygenase pathway of arachidonic acid metabolism and a leukotriene D4 antagonist, at a dose of 10 mg (direct intratracheal administration) significantly inhibited the airway resistance (RL) component of the bronchoconstriction induced by PAF in neonatally-immunized rabbits. Doses of 10 mg, 3 mg and 1 mg PF 5901 (direct intratracheal administration) were sufficient to inhibit significantly the PAF-induced increase in airways responsiveness to inhaled histamine in immunized rabbits. PF 5901 however, failed to alter the pulmonary cell infiltration induced by PAF,as assessed by BAL.5. We suggest from the results of the present study that PAF induces consistent and long-lasting increases in airways responsiveness to histamine in immunized rabbits, which is mediated, at least in part, by products of the 5-lipoxygenase metabolic pathway. Furthermore, the inability of PF 5901 to inhibit the influx of inflammatory cells into the airway lumen following PAF challenge may suggest that bronchial hyperresponsiveness and cellular infiltration are not strictly associated events.

The effect of R 15.7/HO, an anti-CD18 antibody, on the late airway response and airway hyperresponsiveness in an allergic rabbit model.

1. The effects of a mouse (IgG1 fraction) anti-CD 18 neutralizing antibody (R15.7) on allergen-induced late airway response (LAR), airway hyperresponsiveness (AHR) and cellular recruitment were investigated in an allergic rabbit model. 2. Litter-matched NZW rabbits immunized within 24 h of birth with Alternaria tenuis (i.p.) and subsequently exposed to the allergen (i.p.) for the first 3 months of life were challenged with inhaled allergen as adult rabbits. Lung function in terms of dynamic compliance (Cdyn; ml cmH2O-1) and total lung resistance (RL; cmH2O-1 s-1) was monitored for 6 h following the allergen challenge. On day 16, separate groups of rabbits were pretreated with either control antibody (a non-binding mouse IgG1, 1 mg kg-1, i.v.) or R15.7 (1 mg kg-1, i.v.) and 1 h later all were challenged with Alternaria tenuis and lung function monitored thereafter. Airway responsiveness to inhaled histamine was assessed by measuring RL and Cdyn 24 h before and after allergen challenge and bronchoalveolar lavage (BAL) was also performed 24 h before and after allergen challenge. 3. Pretreatment of rabbits with the control antibody had no effect on the LAR as measured by AUC (Cdyn, 0-6 h). However, the magnitude of the LAR following treatment with R15.7 was significantly reduced when compared to LAR demonstrated on 1st challenge (P < 0.001) or to that of the control group on both challenges (P < 0.01). 4. In control antibody pretreated rabbits allergen induced a significant 3.4 fold reduction in the PC50 response to inhaled histamine in terms of RL changes (P < 0.05) and a significant 2.1 fold reduction in PC35 response to inhaled histamine in terms of Cdyn changes (P < 0.05). However, in anti-CD 18 antibody pretreated rabbits there was no significant change in responsiveness to histamine 24 h following allergen, as assessed by either RL PC50 or Cdyn PC35. 5. Allergen challenge induced a significant increase in eosinophil and neutrophil numbers (P < 0.05) in rabbits pre-treated with control antibody, whereas treatment with R15.7 significantly inhibited this increase in the numbers of both cell types. 6. This study demonstrates that the neutralization of CD-18 molecules reduces allergen-induced infiltration of both eosinophils and neutrophils into the airways and abolishes the accompanying LAR and AHR. These results provide evidence to support a role for CD-18 adhesion molecules in the transmigration of inflammatory cells into airways.

Effect of PF 10040 on PAF-induced airway responses in neonatally immunized rabbits.

1. PF 10040 displaced [3H]-PAF from binding sites on rabbit platelets with an IC50 = 1.07 x 10(-5) M, which was approximately three orders of magnitude below that of a standard PAF antagonist WEB 2086 (IC50 = 4.23 x 10(-9) M). 2. PF 10040 at doses of 5 and 10 mg (direct intratracheal administration) had no effect on the acute bronchoconstriction induced by PAF in neonatally immunized rabbits (airway resistance RL or dynamic compliance Cdyn). However, the PAF-induced increase in airway responsiveness to inhaled histamine was significantly inhibited (RL and Cdyn) by both doses of PF 10040. 3. PF 10040 (5 and 10 mg) significantly inhibited the total pulmonary cell infiltration and neutrophil influx induced by PAF as assessed by bronchoalveolar lavage. PAF-induced eosinophil infiltration into the airways was significantly inhibited in rabbits that received only 10 mg PF 10040. 4. We suggest from the results of the present study that PF 10040 does not exert an inhibitory effect on PAF-induced airway responses solely via antagonism of the PAF receptor located on platelets, as PF 10040 significantly inhibited PAF-induced airway hyperresponsiveness in the absence of an effect on the acute bronchospasm induced by PAF. 5. We provide further evidence that pulmonary eosinophil infiltration and the development of airway hyperresponsiveness are not causally related events as the lower dose of PF 10040 (5 mg) significantly inhibited PAF-induced airway hyperresponsiveness yet was without effect on the eosinophil influx.

Effect of a 5-lipoxygenase inhibitor and leukotriene antagonist (PF 5901) on antigen-induced airway responses in neonatally immunized rabbits.

1. The effect of a single intratracheal dose (10 mg) of PF 5901 (2-[3(1-hydroxyhexyl) phenoxymethyl] quinoline hydrochloride, a specific inhibitor of the 5-lipoxygenase pathway of arachidonic acid metabolism and a leukotriene D4 antagonist) on airway changes induced in response to Alternaria tenuis aerosol challenge was assessed in adult rabbits neonatally immunized. Leukotriene generation was determined in vivo by measuring leukotriene B4 (LTB4) levels in bronchoalveolar lavage (BAL) fluid and ex vivo by measuring calcium ionophore-stimulated production of LTB4 in whole blood. 2. While PF 5901 (10 mg) had no significant effect on the acute bronchoconstriction induced by antigen, this dose was sufficient to inhibit significantly the increase in airway responsiveness to inhaled histamine 24 h following antigen challenge (P < 0.05). 3. Total leucocyte infiltration into the airways induced by antigen, as assessed by bronchoalveolar lavage, was significantly inhibited by pretreatment with PF 5901 (10 mg). However, the pulmonary infiltration of neutrophils and eosinophils induced by antigen was unaltered by prior treatment with PF 5901 (10 mg). 4. PF 5901 (10 mg) had no effect on ex vivo LTB4 synthesis in whole blood. However, the antigen-induced increase in LTB4 levels in BAL 24 h following challenge was significantly inhibited (P < 0.05). 5. We suggest from the results of the present study that the antigen-induced airway hyperresponsiveness to inhaled histamine in immunized rabbits is mediated, at least in part, by products of the 5-lipoxygenase metabolic pathway, and is not dependent on the extent of eosinophil or neutrophil influx into the airway lumen.

Effects of theophylline and rolipram on antigen-induced airway responses in neonatally immunized rabbits.

1. The effects of the xanthine, theophylline, a non-selective phosphodiesterase (PDE) inhibitor, and the phosphodiesterase type 4 (PDE 4) inhibitor, rolipram, were evaluated in a model of antigen-induced airway responses in the allergic rabbit. 2. Adult litter-matched NZW rabbits (2.5-3.9 kg), immunized within 24 h of birth with Alternaria tenuis antigen, were pretreated twice daily for 3 days with theophylline (3 mg kg-1, i.p) or rolipram (1 mg kg-1, i.p) prior to antigen challenge (Alternaria tenuis). For each drug-treated group, a parallel group of rabbits were pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled histamine and bronchoalveolar lavage (BAL) was performed 24 h before and after antigen-challenge. 3. Basal lung function in terms of resistance (RL, cmH2O 1(-1)s-1) and dynamic compliance (Cdyn, ml cmH2O-1) were unaltered by pretreatment with theophylline or rolipram compared to their respective vehicles 24 h prior to or post antigen challenge. 4. The acute bronchoconstriction induced by inhaled Alternaria tenuis aerosol was unaffected by pretreatment with theophylline or rolipram. 5. Airway hyperresponsiveness to inhaled histamine was indicated by reduced RL PC50 (2.4-3.5 fold) and Cdyn PC35 (2.5-2.6 fold) values 24 h after antigen challenge. Treatment with rolipram, but not theophylline, prevented the increase in responsiveness to inhaled histamine 24 h after antigen challenge. 6. Total cells per ml of BAL fluid increased 24 h after antigen challenge due to the recruitment of neutrophils and eosinophils. Antigen-induced increases in pulmonary neutrophils were unaffected; however, eosinophils were reduced 57.5% in theophylline and 82% in rolipram-treated rabbits. 7. Inhalation of Alternaria tenuis aerosol elicits an acute bronchoconstriction, followed 24 h later by an increased responsiveness to inhaled histamine and pulmonary neutrophil and eosinophil recruitment in the immunized rabbit. With the dosing regimes used, both rolipram and theophylline inhibited eosinophil recruitment, whilst only rolipram prevented the development of airway hyperresponsiveness. Neither agent inhibited the acute bronchoconstriction due to inhaled antigen.

Effect of the glucocorticosteroid budesonide and a novel phosphodiesterase type 4 inhibitor CDP840 on antigen-induced airway responses in neonatally immunised rabbits.

1. The effects of the inhaled corticosteroid budesonide and a novel PDE 4 inhibitor CDP840 given systematically, were evaluated in a model of antigen-induced airway inflammation in the rabbit. 2. Adult litter-matched NZW rabbits (2.4-3.5 kg) immunised within 24 h of birth with Alternaria tenuis antigen were pretreated with budesonide (total dose 100 micrograms, inhaled over 2 days) or CDP840 (total dose 7 mg kg-1, i.p. over 3 days), before antigen challenge. For each drug-treated group a parallel group of rabbits was pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled histamine was assessed and bronchoalveolar lavage (BAL) performed 24 h before and after antigen challenge. 3. Basal lung function in terms of total lung resistance (RL; cmH2O l 1s-1) and dynamic compliance (Cdyn; ml cmH2O-1) were unaltered by pretreatment with budesonide or CDP840 compared to their respective vehicles 24 h before or after antigen challenge. 4. The RL component of the acute bronchoconstriction induced by inhaled Alternaria tenuis aerosol was unaffected by pretreatment with budesonide. However, budesonide prevented the fall in Cdyn due to antigen. Treatment with CDP840 significantly reduced antigen-induced acute bronchoconstriction in terms of both RL and Cdyn. 5. Airway hyperresponsiveness (AHR) to inhaled histamine was indicated by reduced RL PC50 (2.4-4.5 fold) and Cdyn PC35 (2.1-3.9 fold) values 24 h after antigen challenge. Treatment with either budesonide or CDP840 abolished the antigen-induced increase in responsiveness to inhaled histamine. 6. Total cells recovered per ml of BAL fluid increased 24 h after antigen challenge. Antigen-induced pulmonary eosinophilia was reduced (93%) in budesonide and (85%) in CDP840 treated rabbits. Antigen-induced increases in neutrophil numbers were reduced (76%) with budesonide but not CDP840 pretreatment. 7. Inhalation of Alternaria tenuis aerosol elicited an acute bronchoconstriction, followed 24 hours later by an increased responsiveness to inhaled histamine and pulmonary neutrophil and eosinophil recruitment. CDP840 was more effective than budesonide in preventing the antigen-induced increase in total lung resistance (RL); however, both drugs prevented the antigen-induced reduction in dynamic compliance (Cdyn). CDP840 and budesonide also prevented antigen-induced AHR and eosinophilia in the immunised rabbit.

Capsaicin pre-treatment prevents the development of antigen-induced airway hyperresponsiveness in neonatally immunised rabbits.

The effect of a 3-day pre-treatment regime of capsaicin (8-methyl-N-vanillyl-6-nonenamide) (80 mg/kg s.c.) on airway changes induced by Alternaria tenuis aerosol challenge 3 days later was assessed in adult rabbits immunised from birth to the age of 3 months. Pre-treatment with capsaicin did not alter basal lung function or basal responsiveness to inhaled histamine. While capsaicin had no significant effect on the acute bronchoconstriction induced by antigen, this dose was sufficient to significantly inhibit the increase in airway responsiveness to inhaled histamine achieved 24 h following antigen challenge. The pulmonary recruitment of neutrophils and eosinophils induced by antigen was unaltered by prior treatment with capsaicin. In vitro contractile responsiveness to methacholine was not significantly different in bronchial tissues removed from capsaicin- and vehicle-pre-treated rabbits. In addition, there were no significant differences in responses to methacholine in preparations denuded of epithelium. Contraction of bronchial tissue induced by exogenously applied capsaicin in vitro, although modest, was significantly inhibited in capsaicin-pre-treated animals. In vehicle-pre-treated rabbits, contraction induced by a second challenge with capsaicin 45 min later was significantly reduced to a level that made responses not significantly different from those obtained in capsaicin-pre-treated tissues. The results of the present study demonstrate that antigen-induced airway hyperresponsiveness to inhaled histamine in immunised rabbits is inhibited by prior treatment with capsaicin. These findings suggest the involvement of capsaicin-sensitive nerves in antigen-induced airway hyperresponsiveness but not acute bronchospasm or cell infiltration induced by antigen.

A novel animal model for investigating persistent airway hyperresponsiveness.

The present study investigates the development and maintenance of airway hyperresponsiveness in neonatally immunized rabbits. Rabbits were immunized within 24 hr of birth with the antigen Alternaria tenuis together with aluminum hydroxide as an adjuvant, followed by repeated antigen and adjuvant administration up to 3 months of age. Anesthetized, spontaneously breathing rabbits immunized according to this protocol exhibited a 3.7- (p < 0.01) and 1.8-fold (p < 0.05) increase in airway responsiveness to inhaled histamine when compared with groups of naive or sham-immunized rabbits, respectively. In the absence of further antigen challenge, these changes in airway responsiveness to histamine in a subpopulation of antigen-immunized rabbits persisted for up to 12 months of age. This hyperresponsiveness was not associated with an alteration in either total or differential inflammatory cell numbers as assessed by bronchoalveolar lavage (BAL), and no significant differences in isolated bronchial smooth muscle responsiveness to methacholine, histamine, theophylline, or electrical field stimulation were observed. These results demonstrate that neonatal immunization of rabbits with Alternaria tenuis can lead to the development of persistent airway hyperresponsiveness, and that the maintenance of this state is unrelated to either a detectable alteration in cellular infiltration within the airway lumen or changes in bronchial smooth muscle responsiveness. It is suggested that neonatal exposure to antigen and adjuvant may be important determinants for the development of persistent airway hyperresponsiveness. This animal model may provide a useful way to investigate the effects of drugs on airway hyperresponsiveness.

Adaptation of coenzyme stimulation assays for the nutritional assessment of vitamins B1, B2 and B6 using the Cobas Bio centrifugal analyser.

Adaptation of coenzyme stimulation assays for the nutritional assessment of thiamine, riboflavin and pyridoxine on the Cobas Bio centrifugal analyser are described. Whole blood was collected into acid-citrate dextrose, which preserves the erythrocytes, prior to assay for several days. Washed erythrocytes stored at -70 degrees C and subsequently thawed, showed altered enzyme activities. The methods offer improved precision over existing procedures and take advantage of the high throughput capabilities of the instrumentation.

Adverse reactions during intravenous urography: are these due to histamine release?

The effects of four different radiographic contrast media (Urovison 58%, Hexabrix 320, Iopamiro 370 and Omnipaque 300) have been examined with respect to histamine release, cardiovascular changes and adverse drug reaction (ADR) in a group of 200 patients undergoing intravenous urography. Each patient received only one of the four agents, which were allocated on a random basis. Urovison produced the greatest number of ADRs. Iopamiro caused the least. No significant correlation between the magnitude of the change in plasma histamine following injection of radiographic contrast medium and the production of a particular ADR could be demonstrated. Heart rate increased significantly following the administration of Urovison, Hexabrix and Iopamiro in the absence of any appreciable change in blood pressure. These results and our earlier findings would favour the use of the low-osmolality contrast media in intravenous urography to minimize ADRs, histamine release and patient discomfort.

The provenances of asteroids, and their contributions to the volatile inventories of the terrestrial planets.

Determining the source(s) of hydrogen, carbon, and nitrogen accreted by Earth is important for understanding the origins of water and life and for constraining dynamical processes that operated during planet formation. Chondritic meteorites are asteroidal fragments that retain records of the first few million years of solar system history. The deuterium/hydrogen (D/H) values of water in carbonaceous chondrites are distinct from those in comets and Saturn's moon Enceladus, implying that they formed in a different region of the solar system, contrary to predictions of recent dynamical models. The D/H values of water in carbonaceous chondrites also argue against an influx of water ice from the outer solar system, which has been invoked to explain the nonsolar oxygen isotopic composition of the inner solar system. The bulk hydrogen and nitrogen isotopic compositions of CI chondrites suggest that they were the principal source of Earth's volatiles.

Tissint martian meteorite: a fresh look at the interior, surface, and atmosphere of Mars.

Tissint (Morocco) is the fifth martian meteorite collected after it was witnessed falling to Earth. Our integrated mineralogical, petrological, and geochemical study shows that it is a depleted picritic shergottite similar to EETA79001A. Highly magnesian olivine and abundant glass containing martian atmosphere are present in Tissint. Refractory trace element, sulfur, and fluorine data for the matrix and glass veins in the meteorite indicate the presence of a martian surface component. Thus, the influence of in situ martian weathering can be unambiguously distinguished from terrestrial contamination in this meteorite. Martian weathering features in Tissint are compatible with the results of spacecraft observations of Mars. Tissint has a cosmic-ray exposure age of 0.7 ± 0.3 million years, consistent with those of many other shergottites, notably EETA79001, suggesting that they were ejected from Mars during the same event.

A reduced organic carbon component in martian basalts.

The source and nature of carbon on Mars have been a subject of intense speculation. We report the results of confocal Raman imaging spectroscopy on 11 martian meteorites, spanning about 4.2 billion years of martian history. Ten of the meteorites contain abiotic macromolecular carbon (MMC) phases detected in association with small oxide grains included within high-temperature minerals. Polycyclic aromatic hydrocarbons were detected along with MMC phases in Dar al Gani 476. The association of organic carbon within magmatic minerals indicates that martian magmas favored precipitation of reduced carbon species during crystallization. The ubiquitous distribution of abiotic organic carbon in martian igneous rocks is important for understanding the martian carbon cycle and has implications for future missions to detect possible past martian life.

Airway responsiveness in an allergic rabbit model.

BACKGROUND: Animal models of allergy and bronchial hyperresponsiveness (BHR) are useful in researching pulmonary diseases and evaluating drug effects on the airways. Neonatally immunised rabbits exhibit several features of asthma as adults, including early and late airway responses following antigen challenge, oedema and inflammatory cell infiltration into the lung, BHR to inhaled histamine and methacholine (compared with naïve rabbits) and exacerbations of BHR following antigen challenge. Therefore this model can be used to investigate the underlying mechanisms of BHR and for the preclinical evaluation of new drugs for the treatment of asthma. AIM: To describe the characteristics of airway responses in a rabbit model of allergic inflammation and to evaluate the relationship between skin test reactivity to antigen, airway inflammation and BHR. METHODS: New Zealand White rabbits were neonatally immunised against Alternaria tenius. At 3 months of age, airway responsiveness was measured to aerosolised histamine, methacholine or allergen. Bronchoalveolar lavage (BAL) was performed and cell counts recorded. Direct skin tests were performed to assess skin reactivity to allergen and passive cutaneous anaphylaxis (PCA) tests were performed to determine titres of circulating IgE. RESULTS: In a population of allergic rabbits, allergen challenge induced a significant bronchoconstriction, airway inflammation and BHR. Skin test responsiveness to allergen did not correlate with various indices of pulmonary mechanics e.g. baseline sensitivity to methacholine and histamine, or allergen-induced BHR. In contrast, skin test responsiveness did predict airway inflammation as assessed by measurements of eosinophil recruitment to the lung. CONCLUSION: The allergic rabbit is a useful model to further our understanding of allergic diseases. Recording lung function using a minimally invasive procedure allows repeated measurements to be made in rabbits longitudinally, and each animal may thus be used as its own control. Our observations do not support the use of skin responsiveness to allergen as a predictor of airway sensitivity as we observed no correlation between skin sensitivity and airway responsiveness to inhaled histamine, methacholine or allergen. However, skin reactivity did predict airway inflammation as assessed by measurements of eosinophil recruitment to the lung. Our results also further highlight the likely dissociation between airway inflammation and BHR.