Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase

Mobilization of bone marrow eosinophils is a critical early step in their trafficking to the lung during allergic inflammatory reactions. We have shown previously that the cytokine interleukin (IL)-5, generated during an allergic inflammatory reaction in the guinea pig, acts systemically to mobilize eosinophils from the bone marrow. Here, we have investigated the mechanisms underlying this release process. Examination by light and electron microscopy revealed the rapid migration of eosinophils from the hematopoietic compartment and across the bone marrow sinus endothelium in response to IL-5. Using an in situ perfusion system of the guinea pig hind limb, we showed that IL-5 stimulated a dose-dependent selective release of eosinophils from the bone marrow. Eosinophils released from the bone marrow in response to IL-5 expressed increased levels of β2 integrin and a decrease in L-selectin, but no change in α4 integrin levels. A β2 integrin–blocking antibody markedly inhibited the mobilization of eosinophils from the bone marrow stimulated by IL-5. In contrast, an α4 integrin blocking antibody increased the rate of eosinophil mobilization induced by IL-5. In vitro we demonstrated that IL-5 stimulates the selective chemokinesis of bone marrow eosinophils, a process markedly inhibited by two structurally distinct inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. Wortmannin was also shown to block eosinophil release induced by IL-5 in the perfused bone marrow system. The parallel observations on the bone marrow eosinophil release process and responses in isolated eosinophils in vitro suggest that eosinophil chemokinesis is the driving force for release in vivo and that this release process is regulated by α4 and β2 integrins acting in opposite directions

Dual tasking impairments are associated with striatal pathology in Huntington’s disease

Background: Recent findings suggest that individuals with Huntington’s disease (HD) have an impaired capacity to execute cognitive and motor tasks simultaneously, or dual task, which gradually worsens as the disease advances. The onset and neuropathological changes mediating impairments in dual tasking in individuals with HD are unclear. The reliability of dual tasking assessments for individuals with HD is also unclear. Objectives: To evaluate differences in dual tasking performance between individuals with HD (presymptomatic and prodromal) and matched controls, to investigate associations between striatal volume and dual tasking performance, and to determine the reliability of dual tasking assessments. Methods: Twenty individuals with HD (10 presymptomatic and 10 prodromal) and 20 healthy controls were recruited for the study. Individuals undertook four single and dual task assessments, comprising motor (postural stability or force steadiness) and cognitive (simple or complex mental arithmetic) components, with single and dual tasks performed three times each. Participants also undertook a magnetic resonance imaging assessment. Results: Compared to healthy controls, individuals with presymptomatic and prodromal HD displayed significant deficits in dual tasking, particularly cognitive task performance when concurrently undertaking motor tasks (P \u3c 0.05). The observed deficits in dual tasking were associated with reduced volume in caudate and putamen structures (P \u3c 0.05),however, not with clinical measures of disease burden. An analysis of the reliability of dual tasking assessments revealed moderate to high test–retest reliability [ICC: 0.61-0.99] for individuals with presymptomatic and prodromal HD and healthy controls. Conclusions: Individuals with presymptomatic and prodromal HD have significant deficits in dual tasking that are associated with striatal degeneration. Findings also indicate that dual tasking assessments are reliable in individuals presymptomatic and prodromal HD and healthy controls

Rate of torque development and striatal shape in individuals with prodromal Huntington\u27s disease

The aim of the present study was to quantify explosive joint torque or the ability to develop joint torque rapidly, typically measured as the rate of torque development, in individuals with prodromal Huntington’s disease and healthy controls and its associations with measures of disease burden and striatal pathology. Twenty prodromal Huntington’s disease and 19 healthy control individuals volunteered for this study. Plantar flexor isometric rate of torque development values were evaluated using isokinetic dynamometry. Pathological changes in striatal shape were evaluated using magnetic resonance imaging. Disease burden was evaluated using the disease burden score and cytosine-adenine-guanine age product score. No statistical differences in the rate of torque development were observed between individuals with prodromal Huntington’s disease and healthy controls. However, significant associations were observed between the rate of torque development values and measures of disease burden (r = −0.42 to −0.69) and striatal pathology (r = 0.71–0.60) in individuals with prodromal Huntington’s disease. We found significant associations between lower rate of torque development values and greater striatal shape deflation and disease burden and striatal pathology in individuals with prodromal Huntington’s disease. While no significant differences in the rate of torque development were found between prodromal Huntington’s disease and healthy controls, the noted associations suggest that differences may emerge as the disease advances, which should be investigated longitudinally in future studies

Polarimetric Properties of the Crab Pulsar between 1.4 and 8.4 GHz

New polarimetric observations of the Crab pulsar at frequencies between 1.4 and 8.4 GHz are presented. Additional pulse components discovered in earlier observations (Moffett & Hankins 1996, astro-ph/9604163) are found to have high levels of linear polarization, even at 8.4 GHz. No abrupt sweeps in position angle are found within pulse components; however, the position angle and rotational phase of the interpulse do change dramatically between 1.4 and 4.9 GHz. The multi-frequency profile morphology and polarization properties indicate a non-standard origin of the emission. Several emission geometries are discussed, but the one favored locates sites of emission both near the pulsar surface and in the outer magnetosphere.Comment: 20 pages, 7 postscript figures, uses aaspp4 Latex style. To appear in Volume 522 of The Astrophysical Journa

Human Multidrug-Resistant Salmonella Newport Infections, Wisconsin, 2003–2005

We conducted a retrospective study of Salmonella Newport infections among Wisconsin residents during 2003–2005. Multidrug resistance prevalence was substantially greater in Wisconsin than elsewhere in the United States. Persons with multidrug-resistant infections were more likely than persons with susceptible infections to report exposure to cattle, farms, and unpasteurized milk

Kinetics of Eotaxin Generation and Its Relationship to Eosinophil Accumulation in Allergic Airways Disease: Analysis in a Guinea Pig Model In Vivo

Challenge of the airways of sensitized guinea pigs with aerosolized ovalbumin resulted in an early phase of microvascular protein leakage and a delayed phase of eosinophil accumulation in the airway lumen, as measured using bronchoalveolar lavage (BAL). Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h. Eosinophil numbers in the tissue correlated with eotaxin levels until 6 h but eosinophils persisted until the last measurement time point at 24 h. In contrast, few eosinophils appeared in BAL over the first 12 h, major trafficking through the airway epithelium occurring at 12–24 h when eotaxin levels were low. Constitutive eotaxin was present in BAL fluid. Both constitutive and allergen-induced eosinophil chemoattractant activity in BAL fluid was neutralized by an antibody to eotaxin. Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining. Allergen challenge of the lung resulted in a rapid release of bone marrow eosinophils into the blood. An antibody to IL-5 suppressed bone marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin levels. Thus, IL-5 and eotaxin appear to cooperate in mediating a rapid transfer of eosinophils from the bone marrow to the lung in response to allergen challenge

Human Salmonella and Concurrent Decreased Susceptibility to Quinolones and Extended-Spectrum Cephalosporins

For complicated infections, decreased susceptibility could compromise treatment with drugs from either antimicrobial class

Predation and infanticide influence ideal free choice by a parrot occupying heterogeneous tropical habitats

The ideal free distribution (IFD) predicts that organisms will disperse to sites that maximize their fitness based on availability of resources. Habitat heterogeneity underlies resource variation and influences spatial variation in demography and the distribution of populations. We relate nest site productivity at multiple scales measured over a decade to habitat quality in a box-nesting population of Forpus passerinus (green-rumped parrotlets) in Venezuela to examine critical IFD assumptions. Variation in reproductive success at the local population and neighborhood scales had a much larger influence on productivity (fledglings per nest box per year) than nest site or female identity. Habitat features were reliable cues of nest site quality. Nest sites with less vegetative cover produced greater numbers of fledglings than sites with more cover. However, there was also a competitive cost to nesting in high-quality, low-vegetative cover nest boxes, as these sites experienced the most infanticide events. In the lowland local population, water depth and cover surrounding nest sites were related with F. passerinus productivity. Low vegetative cover and deeper water were associated with lower predation rates, suggesting that predation could be a primary factor driving habitat selection patterns. Parrotlets also demonstrated directional dispersal. Pairs that changed nest sites were more likely to disperse from poor-quality nest sites to high-quality nest sites rather than vice versa, and juveniles were more likely to disperse to, or remain in, the more productive of the two local populations. Parrotlets exhibited three characteristics fundamental to the IFD: habitat heterogeneity within and between local populations, reliable habitat cues to productivity, and active dispersal to sites of higher fitness

Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements

Tripartite integrative and conjugative elements (ICE3) are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases–or recombination directionality factors—RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a “master controller” of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer

Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

The molecular mechanisms that drive mucosal T helper type 2 (T[subscript H]2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell–derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T[subscript H]2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T[subscript H]2 responses