Robustness trade-offs and host–microbial symbiosis in the immune system

The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases

Technology mediator: a new role for the reference librarian?

The Arizona Health Sciences Library has collaborated with clinical faculty to develop a federated search engine that is useful for meeting real-time clinical information needs. This article proposes a technology mediation role for the reference librarian that was inspired by the project, and describes the collaborative model used for developing technology-mediated services for targeted users

Aggravation of allergic airway inflammation by cigarette smoke in mice is CD44-dependent

Background : Although epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation. Methods : Wild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures. Results : In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice. Conclusion : We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics

Environmental enrichment reduces signs of boredom in caged mink

Animals housed in impoverished cages are often labelled 'bored'. They have also been called 'apathetic' or 'depressed', particularly when profoundly inactive. However, these terms are rarely operationally defined and validated. As a negative state caused by under-stimulation, boredom should increase interest in stimuli of all kinds. Apathy (lack of interest), by contrast, should manifest as decreased interest in all stimuli, while anhedonia (loss of pleasure, a depressive symptom) should specifically decrease interest in normally rewarding stimuli. We tested the hypotheses that mink, a model carnivore, experience more boredom, depression-like apathy, or anhedonia in non-enriched (NE) cages than in complex, enriched (E) cages. We exposed 29 subjects (13 E, 16 NE) to ten stimuli categorized a priori as aversive (e.g. air puffs), rewarding (e.g. evoking chasing) or ambiguous/neutral (e.g. candles). Interest in stimuli was assessed via latencies to contact, contact durations, and durations oriented to stimuli. NE mink contacted all stimuli faster (P = 0.003) than E mink, and spent longer oriented to/in contact with them, albeit only significantly so for ambiguous ones (treatment*type P<0.013). With stimulus category removed from statistical models, interest in all stimuli was consistently higher among NE mink (P<0.0001 for all measures). NE mink also consumed more food rewards (P = 0.037). Finally, we investigated whether lying down while awake and stereotypic behaviour (both increased by NE housing) predicted these responses. Lying awake positively co-varied with certain measures of increased exploration. In contrast, stereotypic 'scrabbling' or locomotion (e.g. pacing) did not. Overall, NE mink showed no evidence of apathy or depression, but instead a heightened investigation of diverse stimuli consistent with boredom. This state was potentially indicated by spending much time lying still but awake (although this result requires replication). Boredom can thus be operationalized and assessed empirically in non-human animals. It can also be reduced by environmental enrichment

Atrioventricular and interventricular delay optimization in cardiac resynchronization therapy: physiological principles and overview of available methods

In this review, the physiological rationale for atrioventricular and interventricular delay optimization of cardiac resynchronization therapy is discussed including the influence of exercise and long-term cardiac resynchronization therapy. The broad spectrum of both invasive and non-invasive optimization methods is reviewed with critical appraisal of the literature. Although the spectrum of both invasive and non-invasive optimization methods is broad, no single method can be recommend for standard practice as large-scale studies using hard endpoints are lacking. Current efforts mainly investigate optimization during resting conditions; however, there is a need to develop automated algorithms to implement dynamic optimization in order to adapt to physiological alterations during exercise and after anatomical remodeling

Mechanisms and in vivo functions of contact inhibition of locomotion

Contact inhibition of locomotion (CIL) is a process whereby a cell ceases motility or changes its trajectory upon collision with another cell. CIL was initially characterized more than half a century ago and became a widely studied model system to understand how cells migrate and dynamically interact. Although CIL fell from interest for several decades, the scientific community has recently rediscovered this process. We are now beginning to understand the precise steps of this complex behaviour and to elucidate its regulatory components, including receptors, polarity proteins and cytoskeletal elements. Furthermore, this process is no longer just in vitro phenomenology; we now know from several different in vivo models that CIL is essential for embryogenesis and in governing behaviours such as cell dispersion, boundary formation and collective cell migration. In addition, changes in CIL responses have been associated with other physiological processes, such as cancer cell dissemination during metastasis

Secularist understandings of Pentecostal healing practices in Amsterdam:Developing an intersectional and post-secularist sociology of religion

The past decades have seen an intensification of debate around migrants, gender and sexuality. For the Netherlands, several authors have pointed out how this has given rise to a form of sexual nationalism whereby the idea of being a modern, progressive country is strongly linked to a program of liberal sexual values and offset against a presumably 'backward' migrant who is 'still' religious and traditional. In this article, the author analyses how these dynamics played out in the controversy around HIV-healings or homo healings supposedly taking place in Pentecostal churches in Amsterdam. Media attention highlighted the theme of homosexuality while forgetting the interests of women. This article shows that the sexual nationalism scheme was also operative here, and proposes further developing existing approaches as intersectional 'post-secularist' sociological perspectives aimed at unearthing the ways narratives of modernity, secularization and sexual nationalism structure attitudes towards migrant and religious actors both in social scientific research agendas and among societal actors

Fracture risk with intermittent high-dose oral glucocorticoid therapy.

OBJECTIVE: To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs). METHODS: The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of 'current' and 'no exposure.' The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation. RESULTS: Patients who intermittently received high-dose GCs (daily dose > or =15 mg) and had no or little previous exposure to GCs (cumulative exposure or =30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54-5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49-6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29-25.08). CONCLUSION: Intermittent use of high-dose oral GCs (daily dose > or =15 mg and cumulative exposure or =15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture