Assessment of Surfactant Protein A (SP-A) dependent agglutination

Background: Monomers of the collectin surfactant associated protein-A (SP-A) are arranged in trimers and higher oligomers. The state of oligomerization differs between individuals and likely affects SP-A's functional properties. SP-A can form aggregates together with other SP-A molecules. Here we report and assess a test system for the aggregate forming properties of SP-A in serum and broncho-alveolar lavage samples. Methods: Anti-SP-A antibodies fixed to latex beads bound SP-A at its N-terminal end and allowed the interaction with other SP-A molecules in a given sample by their C-terminal carbohydrate recognition domain (CRD) to agglutinate the beads to aggregates, which were quantified by light microscopy. Results: SP-A aggregation was dependent on its concentration, the presence of calcium, and was dose-dependently inhibited by mannose. Unaffected by the presence of SP-D no aggregation was observed in absence of SP-A. The more complex the oligomeric structure of SP-A present in a particular sample, the better was its capability to induce aggregation at a given total concentration of SP-A. SP-A in serum agglutinated independently of the pulmonary disease; in contrast SP-A in lung lavage fluid was clearly inferior in patients with chronic bronchitis and particularly with cystic fibrosis compared to controls. Conclusions: The functional status of SP-A with respect to its aggregating properties in serum and lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with severe neutrophilic bronchitis was inferior

Masculinity as Governance: police, public service and the embodiment of authority, c. 1700-1850

About the book: Public Men offers an introduction to an exciting new field: the history of masculinities in the political domain and will be essential reading for students and specialists alike with interests in gender or political culture. By building upon new work on gender and political culture, these new case studies explore the gendering of the political domain and the masculinities of the men who have historically dominated it. As such, Public Men is a major contribution to our understanding of the history of Britain between the Eighteenth and the Twentieth centuries

Chronic effects assessment and plasma concentrations of the b-blocker propranolol in fathead minnows (Pimephales promelas)

The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker (beta-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC(hatchability) and LOEC(female GSI) values of 0.1mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC(male wet weight value) of 1.0mg/L, and the LOEC(reproduction) value was 1.0mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0mg/L were 0.34 and 15.00mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0mg/L were greater than the human therapeutic plasma concentration and hence these data very strongly support the fish plasma model proposed by Huggett et al. [Huggett, D.B., Cook, J.C., Ericson, J.F., Williams, R.T., 2003a. A theoretical model for utilizing mammalian pharmacology and safety data to prioritize potential impacts of human pharmaceuticals to fish. Hum. Ecol. Risk Assess. 9, 1789-1799]

Weibel-Palade bodies at a glance

The vascular environment can rapidly alter, and the speed with which responses to both physiological and pathological changes are required necessitates the existence of a highly responsive system. The endothelium can quickly deliver bioactive molecules by regulated exocytosis of its secretory granules, the Weibel−Palade bodies (WPBs). WPBs include proteins that initiate both haemostasis and inflammation, as well those that modulate blood pressure and angiogenesis. WPB formation is driven by von Willebrand factor, their most abundant protein, which controls both shape and size of WPBs. WPB are generated in a range of sizes, with the largest granules over ten times the size of the smallest. In this Cell Science at a Glance and the accompanying poster, we discuss the emerging mechanisms by which WPB size is controlled and how this affects the ability of this organelle to modulate haemostasis. We will also outline the different modes of exocytosis and their polarity that are currently being explored, and illustrate that these large secretory organelles provide a model for how elements of secretory granule biogenesis and exocytosis cooperate to support a complex and diverse set of functions

High prevalence of ST-elevation, early repolarization, and left ventricular hypertrophy during the eligibility assessment for an HIV vaccine trial in young, healthy Tanzanians

BACKGROUND: Vaccinia based immunizations have caused myo/pericarditis and vaccine study volunteers are monitored by ECG. We report ECG outcome obtained during the screening period for an HIV vaccine trial. METHODS: ECG was performed in healthy Tanzanian volunteers. ECG abnormalities and findings interfering with the interpretation of myo/pericarditis were subject to study ineligibility. We determined the prevalence of left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon (SL) or the Cornell index, ST-elevations and early repolarization (ERP) in association with gender, age, BMI and body height by regression analysis adjusted for gender and age. RESULTS: In 257 volunteers (median age 23 years, 63% males) overall positivity for LVH defined by SL or Cornell criteria was seen in 20.6% and 3.5%, ST-elevations ≥ 0.1 mV or ≥ 0.2 mV in 77.8% and 38.1%, and ERP in 23.4%. Positive SL criteria were associated with male gender (PR 7.84, p < 0.001) and lower age (PR 0.70, p = 0.002), and associated with increased body height and lower BMI in univariate analysis. Positive Cornell criteria were only associated with lower age (PR 0.44, p = 0.010). ST-elevations ≥ 0.2 mV were associated with male gender (PR 8.05, p < 0.001) and lower age (PR 0.81, p = 0.003), and ERP with male gender (PR 2.86, p < 0.001). Vaccine study ineligibility due to ECG findings was concluded in 22.1% of the screening population. CONCLUSIONS: High prevalence of LVH according to SL in association with ST-elevation and ERP is especially found in young and male Africans. ECG variations need to be considered for eligibility criteria in studies investigating potential cardiotoxic agents in Africa

Elevated CO₂ does not increase eucalypt forest productivity on a low-phosphorus soil

Rising atmospheric CO2 stimulates photosynthesis and productivity of forests, offsetting CO2 emissions. Elevated CO2 experiments in temperate planted forests yielded ~23% increases in productivity over the initial years. Whether similar CO2 stimulation occurs in mature evergreen broadleaved forests on low-phosphorus (P) soils is unknown, largely due to lack of experimental evidence. This knowledge gap creates major uncertainties in future climate projections as a large part of the tropics is P-limited. Here,we increased atmospheric CO2 concentration in a mature broadleaved evergreen eucalypt forest for three years, in the first large-scale experiment on a P-limited site. We show that tree growth and other aboveground productivity components did not significantly increase in response to elevated CO2 in three years, despite a sustained 19% increase in leaf photosynthesis. Moreover, tree growth in ambient CO2 was strongly P-limited and increased by ~35% with added phosphorus. The findings suggest that P availability may potentially constrain CO2-enhanced productivity in P-limited forests; hence, future atmospheric CO2 trajectories may be higher than predicted by some models. As a result, coupled climate-carbon models should incorporate both nitrogen and phosphorus limitations to vegetation productivity in estimating future carbon sinks

Background risk of breast cancer and the association between physical activity and mammographic density

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Delayed self-recognition in children with autism spectrum disorder.

This study aimed to investigate temporally extended self-awareness (awareness of one’s place in and continued existence through time) in autism spectrum disorder (ASD), using the delayed self-recognition (DSR) paradigm (Povinelli et al., Child Development 67:1540–1554, 1996). Relative to age and verbal ability matched comparison children, children with ASD showed unattenuated performance on the DSR task, despite showing significant impairments in theory-of-mind task performance, and a reduced propensity to use personal pronouns to refer to themselves. The results may indicate intact temporally extended self-awareness in ASD. However, it may be that the DSR task is not an unambiguous measure of temporally extended self-awareness and it can be passed through strategies which do not require the possession of a temporally extended self-concept

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

Bilateral spondylolysis of inferior articular processes of the fourth lumbar vertebra: a case report

Lumbar spondylolysis, a well known cause of low back pain, usually affects the pars interarticularis of a lower lumbar vertebra and rarely involves the articular processes. We report a rare case of bilateral spondylolysis of inferior articular processes of L4 vertebra that caused spinal canal stenosis with a significant segmental instability at L4/5 and scoliosis. A 31-year-old male who had suffered from low back pain since he was a teenager presented with numbness of the right lower leg and scoliosis. Plain X-rays revealed bilateral spondylolysis of inferior articular processes of L4, anterolisthesis of the L4 vertebral body, and right lateral wedging of the L4/5 disc with compensatory scoliosis in the cephalad portion of the spine. MR images revealed spinal canal stenosis at the L4/5 disc level. Posterior lumbar interbody fusion of the L4/5 was performed, and his symptoms were relieved