Respiratory adaptations to dead space loading during maximal incremental exercise

We examined the effects of dead space (VD) loading on breathing pattern during maximal incremental exercise in eight normal subjects. Addition of external VD was associated with a significant increase in tidal volume (VT) and decrease in respiratory frequency (f) at moderate and high levels of ventilation (VI); at a VI of 120 l/min, VT and f with added VD were 3.31 +/- 0.33 liters and 36.7 +/- 6.7 breaths/min, respectively, compared with 2.90 +/- 0.29 liters and 41.8 +/- 7.3 breaths/min without added VD. Because breathing pattern does not change with CO2 inhalation during heavy exercise (Gallagher et al. J. Appl. Physiol. 63: 238-244, 1987), the breathing pattern response to added VD is probably a consequence of alteration in the PCO2 time profile, possibly sensed by the carotid body and/or airway-pulmonary chemoreceptors. The increase in VT during heavy exercise with VD loading indicates that the tachypneic breathing pattern of heavy exercise is not due to mechanical limitation of maximum ventilatory capacity at high levels of VT.     

The influence of cell elastic modulus on inertial positions in Poiseuille microflows

Microchannels are used as a transportation highway for suspended cells both in vivo and ex vivo. Lymphatic and cardiovascular systems transfer suspended cells through microchannels within the body, and microfluidic techniques such as lab-on-a-chip devices, flow cytometry, and CAR T-cell therapy utilize microchannels of similar sizes to analyze or separate suspended cells ex vivo. Understanding the forces that cells are subject to while traveling through these channels are important because certain applications exploit these cell properties for cell separation. This study investigated the influence that cytoskeletal impairment has on the inertial positions of circulating cells in laminar pipe flow. Two representative cancer cell lines were treated using cytochalasin D, and their inertial positions were investigated using particle streak imaging and compared between benign and metastatic cell lines. This resulted in a shift in inertial positions between benign and metastatic as well as treated and untreated cells. To determine and quantify the physical changes in the cells that resulted in this migration, staining and nanoindentation techniques were then used to determine the cells’ size, circularity, and elastic modulus. It was found that the cells’ exposure to cytochalasin D resulted in decreased elastic moduli of cells, with benign and metastatic cells showing decreases of 135 ± 91 and 130 ± 60 Pa, respectively, with no change in either size or shape. This caused benign, stiffer cancer cells to be more evenly distributed across the channel width than metastatic, deformable cancer cells; additionally, a decrease in the elastic moduli of both cell lines resulted in increased migration toward the channel center. These results indicate that the elastic modulus may play more of a part in the inertial migration of such cells than previously thought.     

Reducing the Decline in Physical Activity during Pregnancy: A Systematic Review of Behaviour Change Interventions

Purpose

Physical activity (PA) typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change.

Search and Review Methodology

Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT) taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach.

Findings

A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n = 6), structured exercise (n = 6) and education (n = 2). Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls.

Conclusions and Implications

Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy. Range of behaviour change techniques can be implemented to reduce this decline including goals and planning, shaping knowledge and comparison of outcomes. A lack of high quality interventions hampers conclusions of intervention effectiveness.     

Physiological dynamics,reproduction‐maintenance allocations,and life history evolution

Allocation of resources to competing processes of growth, maintenance, or reproduction is arguably a key process driving the physiology of life history trade‐offs and has been shown to affect immune defenses, the evolution of aging, and the evolutionary ecology of offspring quality. Here, we develop a framework to investigate the evolutionary consequences of physiological dynamics by developing theory linking reproductive cell dynamics and components of fitness associated with costly resource allocation decisions to broader life history consequences. We scale these reproductive cell allocation decisions to population‐level survival and fecundity using a life history approach and explore the effects of investment in reproduction or tissue‐specific repair (somatic or reproductive) on the force of selection, reproductive effort, and resource allocation decisions. At the cellular level, we show that investment in protecting reproductive cells increases fitness when reproductive cell maturation rate is high or reproductive cell death is high. At the population level, life history fitness measures show that cellular protection increases reproductive value by differential investment in somatic or reproductive cells and the optimal allocation of resources to reproduction is moulded by this level of investment. Our model provides a framework to understand the evolutionary consequences of physiological processes underlying trade‐offs and highlights the insights to be gained from considering fitness at multiple levels, from cell dynamics through to population growth.     

α-tocopherol inhibits oxidative stress induced by cholestanetriol and 25-hydroxycholesterol in porcine ovarian granulosa cells

The cytotoxicity of oxysterols including 7-ketocholesterol, -epoxide, cholestanetriol and 25-hydroxycholesterol and the possible protecting effect of -tocopherol on cholestanetriol and 25-hydroxycholesterol-induced cytotoxicity were investigated in primary cultures of porcine ovarian granulosa cells. Cell viability as determined by % trypan blue staining and mitochondrial function as determined using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) reduction were decreased significantly after 24 h exposure to 2.5 M -epoxide, cholestanetriol and 25-hydroxycholesterol. 7-ketocholesterol (2.5 M) did not affect cell viability or mitochondrial function under the same culture conditions. The specific activities of catalase and superoxide dismutase, two antioxidant defense enzymes were increased significantly (p < 0.01) following 24 h exposure to 2.5 M concentrations of cholestanetriol while only superoxide dismutase was increased in 25-hydroxycholesterol-treated cells (p < 0.001). Specific activity of glutathione peroxidase was unchanged relative to control cells. Levels of thiobarbituric acid reactive substances remained unchanged after exposure to 7-ketocholesterol, -epoxide, cholestanetriol, 25-hydroxycholesterol and cholesterol. Administration of 1 M -tocopherol to the culture medium significantly improved cell viability and restored both superoxide dismutase and catalase activities to control levels in cholestanetriol -treated cells and only superoxide dismutase in 25-hydroxycholesterol-treated cells. These studies suggest that the cytotoxic nature of physiologically relevant concentrations of cholestanetriol and 25-hydroxycholesterol in granulosa cells is in part due to oxidative stress, but it may be reduced in the presence of a-tocopherol.     

Synthesis and X-ray crystal structure of [Ag(phendio)<Subscript>2</Subscript>]ClO<Subscript>4</Subscript> (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells

The Cu(II) and Ag(I) complexes, [Cu(phendio)₃](ClO₄)₂4H₂O and [Ag(phendio)₂]ClO₄ (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. `Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH<sub>3</sub>CO<sub>2</sub>, AgNO<sub>3</sub> and AgClO<sub>4</sub>.H<sub>2</sub>O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to `metal-free' phendio, simple Ag(I) salts and [Ag(phendio)₂]ClO₄ causes extensive, non-specific DNA cleavage. `Metal-free' phendio and [Ag(phendio)₂]ClO₄ induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells.     

The role of citizen science in monitoring biodiversity in Ireland

Citizen science is proving to be an effective tool in tracking the rapid pace at which our environment is changing over large geographic areas. It is becoming increasingly popular, in places such as North America and some European countries, to engage members of the general public and school pupils in the collection of scientific data to support long-term environmental monitoring. Participants in such schemes are generally volunteers and are referred to as citizen scientists. The Christmas bird count in the US is one of the worlds longest running citizen science projects whereby volunteers have been collecting data on birds on a specific day since 1900. Similar volunteer networks in Ireland have been in existence since the 1960s and were established to monitor the number and diversity of birds throughout the country. More recently, initiatives such as Greenwave (2006) and Nature Watch (2009) invite school children and members of the general public respectively, to record phenology data from a range of common species of plant, insect and bird. In addition, the Irish butterfly and bumblebee monitoring schemes engage volunteers to record data on sightings of these species. The primary purpose of all of these networks is to collect data by which to monitor changes in wildlife development and diversity, and in the case of Greenwave to involve children in hands-on, inquiry-based science. Together these various networks help raise awareness of key environmental issues, such as climate change and loss of biodiversity, while at the same time promote development of scientific skills among the general population. In addition, they provide valuable scientific data by which to track environmental change. Here we examine the role of citizen science in monitoring biodiversity in Ireland and conclude that some of the data collected in these networks can be used to fulfil Ireland’s statutory obligations for nature conservation. In addition, a bee thought previously to be extinct has been rediscovered and a range expansion of a different bee has been confirmed. However, it also became apparent that some of the networks play more of an educational than a scientific role. Furthermore, we draw on experience from a range of citizen science projects to make recommendations on how best to establish new citizen science projects in Ireland and strengthen existing ones.     

Salmonella induces a switched antibody response without germinal centers that impedes the extracellular spread of infection

T-dependent Ab responses are characterized by parallel extrafollicular plasmablast growth and germinal center (GC) formation. This study identifies that, in mice, the Ab response against Salmonella is novel in its kinetics and its regulation. It demonstrates that viable, attenuated Salmonella induce a massive early T-dependent extrafollicular response, whereas GC formation is delayed until 1 mo after infection. The extrafollicular Ab response with switching to IgG2c, the IgG2a equivalent in C57BL/6 mice, is well established by day 3 and persists through 5 wk. Switching is strongly T dependent, and the outer membrane proteins are shown to be major targets of the early switched IgG2c response, whereas flagellin and LPS are not. GC responses are associated with affinity maturation of IgG2c, and their induction is associated with bacterial burden because GC could be induced earlier by treating with antibiotics. Clearance of these bacteria is not a consequence of high-affinity Ab production, for clearance occurs equally in CD154-deficient mice, which do not develop GC, and wild-type mice. Nevertheless, transferred low- and high-affinity IgG2c and less efficiently IgM were shown to impede Salmonella colonization of splenic macrophages. Furthermore, Ab induced during the infection markedly reduces bacteremia. Thus, although Ab does not prevent the progress of established splenic infection, it can prevent primary infection and impedes secondary hemogenous spread of the disease. These results may explain why attenuated Salmonella-induced B cell responses are protective in secondary, but not primary infections.     

Impact of selected Lactobacillus and Bifidobacterium species on Listeria monocytogenes infection and the mucosal immune response

The pathogenesis of Listeria monocytogenes depends on its ability to attach to and invade the gastrointestinal epithelium and subsequently withstand the host immune response. Despite a thorough understanding of the intracellular phase of infection, relatively little is known about how the pathogen behaves in the gastrointestinal tract and whether it is affected by the presence of host commensal microbiota. Lactobacillus and Bifidobacterium are two important genera of the human gut microbiota proposed to possess probiotic effects. Here we demonstrate that probiotic bacteria significantly inhibit subsequent listerial infection in an in vitro C2Bbe1 epithelial cell model. In the case of Lactobacilli, inhibition was due to a combination of acid production and secretion of an as yet unidentified protein. In the case of Bifidobacterium, inhibition was attributable to an extracellular proteinaceous secreted compound. In addition, we observed a significant reduction in interleukin-8 and an increase in IL-10 cytokines secreted from epithelial cells following probiotic pretreatment and subsequent infection with Listeria. A reduction in the infection of epithelial cells and an altered mucosal immune response suggests that probiotic bacteria could be of therapeutic benefit against listerial infection. This study infers a role for probiotic bacteria as an antagonist of Li. monocytogenes infection.