Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response

Gas exchange during exercise in habitually active asthmatic subjects

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency

Increased artery wall stress post-stenting leads to greater intimal thickening

Since the first human procedure in the late 1980s, vascular stent implantation has been accepted as a standard form of treatment of atherosclerosis. Despite their tremendous success, these medical devices are not without their problems, as excessive neointimal hyperplasia can result in the formation of a new blockage (restenosis). Clinical data suggest that stent design is a key factor in the development of restenosis. Additionally, computational studies indicate that the biomechanical environment is strongly dependent on the geometrical configuration of the stent, and therefore possibly involved in the development of restenosis. We hypothesize that stents that induce higher stresses on the artery wall lead to a more aggressive pathobiologic response, as determined by the amount of neointimal hyperplasia. The aim of this investigation was to examine the role of solid biomechanics in the development of restenosis. A combination of computational modeling techniques and in vivo analysis were employed to investigate the pathobiologic response to two stent designs that impose greater or lesser levels of stress on the artery wall. Stent designs were implanted in a porcine model (pigs) for approximately 28 days and novel integrative pathology techniques (quantitative micro-computed tomography, histomorphometry) were utilized to quantify the pathobiologic response. Concomitantly, computational methods were used to quantify the mechanical loads that the two stents place on the artery. Results reveal a strong correlation between the computed stress values induced on the artery wall and the pathobiologic response; the stent that subjected the artery to the higher stresses had significantly more neointimal thickening at stent struts (high stress stent: 0.197 ± 0.020 mm vs. low-stress stent: 0.071 ± 0.016 mm). Therefore, we conclude that the pathobiologic differences are a direct result of the solid biomechanical environment, confirming the hypothesis that stents that impose higher wall stresses will provoke a more aggressive pathobiological response

The morphology, ecology and fungicidal tolerance of Botrytis cinerea isolates

Field isolates of Botrytis cinerea Pers. from tomato crops gave rise to two distinct morphological types after successive single spore isolations; type 1 (T1) characterised by regular, rapidly growing mycelium and type 2 (T2) characterised by sparse, often distorted, slow growing mycelium. The frequency with which isolates produced these morphological types varied considerably. The reaction to benomyl of both types obtained remained the same as that of the parent isolate through successive single spore isolations on fungicide free agar over 10 generations. Benomyl tolerant field isolates could not be distinguished from sensitive isolates on the basis of colony morphology. Examination of 188 isolates of B. cinerea collected from 10 different tomato crops showed that sensitive isolates tended to be more pathogenic to detached tomato cotyledons and grew faster in vitro than tolerant isolates. In vitro and in vivo studies revealed no difference in the competitive ability of benomyl tolerant and sensitive isolates in mixed culture. In a study of 17 Lancashire tomato crops all were found to contain benomyl tolerant strains of B. cinerea although in some cases benzimidazole fungicides had not been used on the nursery for up to three years. Examination of B. cinerea in tomato crops suggested that the majority of stem lesions arose from infected leaf scars and were non-aggressive. Side shoot stumps or scars were also liable to infection and the resulting lesions were more likely to become aggressive than lesions at leaf scars. Conidia were considered to be the major source of inoculum although lesions at leaf scars could take up to 61 days to develop after deleafing. This delay was attributed to latent infection. Artificial infection of the petiole with B. cinerea prior to deleafing greatly reduced the susceptibility of the resulting leaf scar to subsequent attack by B. cinerea. Extracts from infected stems were shown to delay the germination of B. cinerea conidia when compared to extracts from healthy stems. This inhibition of germination was attributed to a resistance factor (RF) produced by the fungus or host in response to infection

Lions and Prions and Deer Demise

Background: Contagious prion diseases – scrapie of sheep and chronic wasting disease of several species in the deer family – give rise to epidemics that seem capable of compromising host population viability. Despite this prospect, the ecological consequences of prion disease epidemics in natural populations have received little consideration. Methodology/Principal Findings: Using a cohort study design, we found that prion infection dramatically lowered survival of free-ranging adult (.2-year-old) mule deer (Odocoileus hemionus): estimated average life expectancy was 5.2 additional years for uninfected deer but only 1.6 additional years for infected deer. Prion infection also increased nearly fourfold the rate of mountain lions (Puma concolor) preying on deer, suggesting that epidemics may alter predator–prey dynamics by facilitating hunting success. Despite selective predation, about one fourth of the adult deer we sampled were infected. High prevalence and low survival of infected deer provided a plausible explanation for the marked decline in this deer population since the 1980s. Conclusion: Remarkably high infection rates sustained in the face of intense predation show that even seemingly complete ecosystems may offer little resistance to the spread and persistence of contagious prion diseases. Moreover, the depression of infected populations may lead to local imbalances in food webs and nutrient cycling in ecosystems in which deer ar

Reliable microsatellite genotyping of the Eurasian badger (Meles meles) using faecal DNA

The potential link between badgers and bovine tuberculosis has made it vital to develop accurate techniques to census badgers. Here we investigate the potential of using genetic profiles obtained from faecal DNA as a basis for population size estimation. After trialling several methods we obtained a high amplification success rate (89%) by storing faeces in 70% ethanol and using the guanidine thiocyanate/silica method for extraction. Using 70% ethanol as a storage agent had the advantage of it being an antiseptic. In order to obtain reliable genotypes with fewer amplification reactions than the standard multiple-tubes approach, we devised a comparative approach in which genetic profiles were compared and replication directed at similar, but not identical, genotypes. This modified method achieved a reduction in polymerase chain reactions comparable with the maximumlikelihood model when just using reliability criteria, and was slightly better when using reliability criteria with the additional proviso that alleles must be observed twice to be considered reliable. Our comparative approach would be best suited for studies that include multiple faeces from each individual. We utilized our approach in a well-studied population of badgers from which individuals had been sampled and reliable genotypes obtained. In a study of 53 faeces sampled from three social groups over 10 days, we found that direct enumeration could not be used to estimate population size, but that the application of mark–recapture models has the potential to provide more accurate results

Evidence for Superfluidity of Ultracold Fermions in an Optical Lattice

The study of superfluid fermion pairs in a periodic potential has important ramifications for understanding superconductivity in crystalline materials. Using cold atomic gases, various condensed matter models can be studied in a highly controllable environment. Weakly repulsive fermions in an optical lattice could undergo d-wave pairing at low temperatures, a possible mechanism for high temperature superconductivity in the cuprates. The lattice potential could also strongly increase the critical temperature for s-wave superfluidity. Recent experimental advances in the bulk include the observation of fermion pair condensates and high-temperature superfluidity. Experiments with fermions and bosonic bound pairs in optical lattices have been reported, but have not yet addressed superfluid behavior. Here we show that when a condensate of fermionic atom pairs was released from an optical lattice, distinct interference peaks appear, implying long range order, a property of a superfluid. Conceptually, this implies that strong s-wave pairing and superfluidity have now been established in a lattice potential, where the transport of atoms occurs by quantum mechanical tunneling and not by simple propagation. These observations were made for unitarity limited interactions on both sides of a Feshbach resonance. For larger lattice depths, the coherence was lost in a reversible manner, possibly due to a superfluid to insulator transition. Such strongly interacting fermions in an optical lattice can be used to study a new class of Hamiltonians with interband and atom-molecule couplings.Comment: accepted for publication in Natur

First anatomical network analysis of fore- and hindlimb musculoskeletal modularity in bonobos, common chimpanzees, and humans

Studies of morphological integration and modularity, and of anatomical complexity in human evolution typically focus on skeletal tissues. Here we provide the first network analysis of the musculoskeletal anatomy of both the fore- and hindlimbs of the two species of chimpanzee and humans. Contra long-accepted ideas, network analysis reveals that the hindlimb displays a pattern opposite to that of the forelimb: Pan big toe is typically seen as more independently mobile, but humans are actually the ones that have a separate module exclusively related to its movements. Different fore- vs hindlimb patterns are also seen for anatomical network complexity (i.e., complexity in the arrangement of bones and muscles). For instance, the human hindlimb is as complex as that of chimpanzees but the human forelimb is less complex than in Pan. Importantly, in contrast to the analysis of morphological integration using morphometric approaches, network analyses do not support the prediction that forelimb and hindlimb are more dissimilar in species with functionally divergent limbs such as bipedal humans

Localization of Fulicin-like Immunoreactivity in the Central Nervous System and Periphery of Biomphalaria glabrata, an Intermediate Host for Schistosomiasis

An estimate of about ten percent of the population worldwide live at risk of contracting the parasitic disease schistosomiasis, or “snail fever”. The digenetic trematode worm species Schistosoma mansoni that is responsible for causing the most common form of intestinal schistosomiasis requires the freshwater snail Biomphalaria glabrata to serve as its primary intermediate host, where it multiplies and develops into its cercarial form that is infectious to humans. Parasitic castration and parasitic gigantism are among some of the profound behavioral changes that the infection of B. glabrata by S. mansoni is known to cause. For this reason, a neural transcriptomics approach was undertaken to determine precursor prohormones that could encode neuropeptides implicated in Biomphalaria reproductive and feeding behaviors. A transcript (1616 nucleotides) was found to encode a putative precursor polypeptide (316 aminoacids) that could give way to the neuropeptide fulicin (Phe–D-Asn-Glu-Phe-Val-NH2; Ohta et al. 1991; Yasuma Kamatani et al. 1995) and five additional related peptides. For this investigation, affinity purified polyclonal antibodies (rabbit) were developed against the anticipated fulicin neuropeptide. Fulicin-like immunoreactivity was observed throughout the central nervous system (CNS) with distinct neurons and clusters on the ventral and dorsal surfaces, as well as in peripheral tissues. Fulicin-like cells of both large and small diameter were present on the dorsal and ventral surfaces of the buccal ganglion. In addition dispersed clusters of small diameter cells were observed in the cerebral and pedal ganglia. However, in the right pleural ganglion no fulicin-like neurons were present, although it was rich in immunoreactive fibers. Within the left parietal and visceral ganglia, clusters of large prominent cells appeared to give rise to axons projecting to the anal and intestinal nerves. Additionally, peripheral tissue of B. glabrata, specifically regions of the mantle, lip and tentacle were rich in fulicin-like immunoreactive fibers and cell bodies. These results suggest that fulicin and other peptides derived from the fulicin precursor could regulate behaviors related to food intake, reproduction, and growth that are altered during the course of infection in this host-parasite system