Development of cell surface saccharides on embryonic pancreatic cells

Using a battery of seven lectin-ferritin conjugates as probes for cell surface glycoconjugates, we have studied the pattern of plasmalemmal differentiation of cells in the embryonic rat pancreas from day 15 in utero to the early postpartum stage. Our results indicate that differentiation of plasmalemmal glycoconjugates on acinar, endocrine, and centroacinar cells is temporally correlated with development and is unique for each cell type, as indicated by lectin-ferritin binding. Specifically, (a) expression of adult cell surface saccharide phenotype can be detected on presumptive acinar cells as early as 15 d in utero, as indicated by soybean agglutinin binding, and precedes development of intracellular organelles characteristic of mature acinar cells; (b) maturation of the plasmalemma of acinar cells is reached after intracellular cytodifferentiation is completed, as indicated by appearance of Con A and fucoselectin binding sites only at day 19 of development; conversely, maturation of the endocrine cell plasmalemma is accompanied by "loss" (masking) of ricinus communis II agglutinin receptors; and (c) binding sites for fucose lectins and for soybean agglutinin are absent on endocrine and centroacinar cells at all stages examined. We conclude that acinar, centroacinar, and endocrine cells develop from a common progenitor cell(s) whose plasmalemmal carbohydrate composition resembles most closely that of the adult centroacinar cell. Finally, appearance of acinar lumina beginning at approximately 17 d in utero is accompanied by differenetiation of apical and basolateral plasmalemmal domains of epithelial cells, as indicated by enhanced binding of several lectin-ferritin conjugates to the apical plasmalemmal, a pattern that persists from this stage through adult life.     

Age-Specific Mortality During the 1918 Influenza Pandemic: Unravelling the Mystery of High Young Adult Mortality

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

“The war is over – and I must go” Egon Schiele, 1890–1918.

     

Analysis of breast implant capsular tissue for crystalline silica and other refractile phases

This study questions previous reports of the presence of micrometer-sized areas of crystalline silica in pathologic tissue sections that are based exclusively on polarized-light microscopy. By using optical principles, it can be argued that it is impossible to identify unambiguously or to detect the birefringence of crystalline silica in 5-microm-thin sections. To clarify whether silicone, amorphous silica, or crystalline silica occurs in micrometer-sized moieties in standard 5-microm-thick tissue sections, one needs to apply a structural means of analysis in addition to optical microscopy. This study recommends the use of the laser Raman spectroscopic technique, which is very well suited to clarify this highly controversial issue in future pathologic studies.     

The cover of living and dead corals from airborne remote sensing

Trends in coral cover are widely used to indicate the health of coral reefs but are costly to obtain from field survey over large areas. In situ studies of reflected spectra at the coral surface show that living and recently dead colonies can be distinguished. Here, we investigate whether such spectral differences can be detected using an airborne remote sensing instrument. The Compact Airborne Spectrographic Imager (Itres Research Ltd, Canada) was flown in two configurations: 10 spectral bands with 1-m² pixels and 6 spectral bands with 0.25-m² pixels. First, we show that an instrument with 10 spectral bands possesses adequate spectral resolution to distinguish living Porites, living Pocillopora spp., partially dead Porites, recently dead Porites (total colony mortality within 6 months), old dead (>6 months) Porites, Halimeda spp., and coralline red algae when there is no water column to confuse spectra. All substrata were distinguished using fourth-order spectral derivatives around 538 nm and 562 nm. Then, at a shallow site (Tivaru) at Rangiroa Atoll, Tuamotu Archipelago (French Polynesia), we show that live and dead coral can be distinguished from the air to a depth of at least 4 m using first- and fourth-order spectral derivatives between 562–580 nm. However, partially dead and recently dead Porites colonies could not be distinguished from an airborne platform. Spectral differences among substrata are then exploited to predict the cover of reef substrata in ten 25-m² plots at nearby Motu Nuhi (max depth 8 m). The actual cover in these plots was determined in situ using quadrats with a 0.01-m² grid. Considerable disparity occurred between field and image-based measures of substrate cover within individual 25-m² quadrats. At this small scale, disparity, measured as the absolute difference in cover between field and remote-sensing methods, reached 25% in some substrata but was always less than 10% for living coral (99% of which consisted of Porites spp.). At the scale of the reef (all ten 25-m² quadrats), however, disparities in percent cover between imagery and field data were less than 10% for all substrata and extremely low for some classes (e.g. <3% for living Porites, recently dead Porites and Halimeda). The least accurately estimated substrata were sand and coralline red algae, which were overestimated by absolute values 7.9% and 6.6%, respectively. The precision of sampling was similar for field and remote-sensing methods: field methods required 19 plots to detect a 10% difference in coral cover among three reefs with a statistical power of 95%. Remote-sensing methods required 21 plots. However, it took 1 h to acquire imagery over 92,500 m² of reef, which represents 3,700 plots of 25 m² each, compared with 3 days to survey 10 such plots underwater. There were no significant differences in accuracy between 1-m² and 0.25-m² image resolutions, suggesting that the advantage of using smaller pixels is offset by reduced spectral information and an increase in noise (noise was observed to be 1.6–1.8 times greater in 0.25-m² pixels). We show that airborne remote sensing can be used to monitor coral and algal cover over large areas, providing that water is shallow and clear, and that brown fleshy macroalgae are scarce, that depth is known independently (e.g. from sonar survey).     

Gene transfer to pre-hematopoietic and committed hematopoietic precursors in the early mouse Yolk Sac: a comparative study between <Emphasis Type="Italic">in situ</Emphasis> electroporation and retroviral transduction

Background  

Hematopoietic development in vertebrate embryos results from the sequential contribution of two pools of precursors independently generated. While intra-embryonic precursors harbour the features of hematopoietic stem cells (HSC), precursors formed earlier in the yolk sac (YS) display limited differentiation and self-renewal potentials. The mechanisms leading to the generation of the precursors in both sites are still largely unknown, as are the molecular basis underlying their different potential. A possible approach to assess the role of candidate genes is to transfer or modulate their expression/activity in both sites. We thus designed and compared transduction protocols to target either native extra-embryonic precursors, or hematopoietic precursors.     

Acetylcholinesterase activity in the earthworm Eisenia andrei at different conditions of carbaryl exposure

Recent reports have stressed the need for a better understanding of earthworm biomarker responses. We aimed at investigating acethylcholinesterase (AChE) activity in the earthworm Eisenia andrei after exposure to carbaryl or its commercial formulation Zoril 5 under different in vitro and in vivo experiments. In addition, lysosome membrane stability was assessed by neutral red retention assay in the same experimental conditions. AChE basal Km and Vm values were about 0.16 mM and 41 nmol min(-1) mg protein(-1), respectively. Carbaryl dose-dependently decreased Vmax, while not affecting Km values. Carbaryl reduced earthworm AChE activity within 1 day of in vivo exposure to contaminated filter paper. Tested on soil, carbaryl inhibited AChE with the maximum effect after 3 days; in contrast, lysosome membrane stability of coelomocytes indicated a maximum toxicity after one day, followed by a recovery. AChE inhibition by Zoril 5 was highest after one day, while lysosome membrane stability declined progressively. In all cases, carbaryl dose-dependently decreased Vmax while not affecting Km values. In conclusion, E. andrei AChE activity assessed in vitro is dose-dependently inhibited by the carbamate compound carbaryl, which acts as a pure competitive inhibitor. In vivo experiments suggested that pure and co-formulated carbaryl have different time and/or dose dependent effects on earthworms. Our results further support the use of AChE inhibition as an indicator of pesticide contamination, to be included in a battery of biomarkers for monitoring soil toxicity.     

European society of intensive care medicine study of therapeutic hypothermia (32-35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial)

Background

Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2) has recently been shown to function as a key regulator. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO) gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates.

Methods/Design

This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy), among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae.

Discussion

Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov Identifier: NCT01255215     

Modelling the population dynamics of <Emphasis Type="Italic">Daphnia obtusa</Emphasis> (Kurz) in Lake Orta (N. Italy) under pre- and post-liming conditions

A mathematical matrix model was formulated to investigate the response of Daphnia obtusa population dynamics to the changes in the water chemistry of Lake Orta before and after the liming operation. Model parameters were estimated from experimental laboratory data. Model analysis showed that water chemistry changes induced by liming affected mainly egg survival and predicted the highest population growth at pH␣6. Whereas increased egg mortality heavily inhibits population growth rate, the model still predicts a long term tendency of the population to increase in number. However, both before and after the liming operation due to high food availability in the laboratory, egg production was higher under all experimental conditions than in the field. When food limitation is accounted for and more realistic, field based estimates of egg production are used, the model predicts the extinction of D. obtusa population in the lake. This suggests that the effects of water chemistry changes on egg mortality had a critical role in the disappearance of D. obtusa from Lake Orta and may even adequately explain the extinction of this population.     

From Demographic Strategies to Mathematical Models: Trends in Population Dynamics Studies of Aquatic Oligochaeta

The existence of a negative relationship between fine sediment infiltration during the incubation period and salmonid embryo survival has often been discussed in the literature. However, few studies have specifically addressed this relationship in the field. We conducted a field experiment to examine the relationship between survival of Atlantic salmon (Salmo salar) embryos contained in incubation baskets and the patterns of fine sediment infiltration into the baskets during the incubation period. The results indicate that survival to pre-eyed (STPE), eyed (STE) and hatched (STH) stages of development were all negatively correlated with the percentage of fine sediment entering the baskets. STPE and STE were most strongly affected by silts and clays (<0.063 mm) although this size class represented only a small fraction of the grain size distribution inside the incubation baskets (0.03–0.41%). STH was most strongly correlated with the infiltration of medium sand (0.25–0.50 mm) material. On average, 66% of the implanted embryos survived to the pre-eyed stage of development compared to 63% for the eyed and 48% for the hatched stages of development.