Dendronized hydroxypropyl cellulose: synthesis and characterization of biobased nanoobjects

Dendronized polymers containing a cellulose backbone have been synthesized with the aim of producing complex molecules with versatile functionalization possibilites and high molecular weight from biobased starting materials. The dendronized polymers were built by attaching premade acetonide-protected 2,2-bis(methylol)propionic acid functional dendrons of generation one to three to a hydroxypropyl cellulose backbone. Deprotection or functionalization of the end groups of the first generation dendronized polymer to hydroxyl groups and long alkyl chains was performed, respectively. The chemical structures of the dendronized polymers were confirmed through analysis using (1)H NMR and FT-IR spectroscopies. From SEC analysis, the dendronized polymers were found to have an increasing polystyrene-equivalent molecular weight up to the second generation ( M n = 50 kg mol (-1)), whereas the polystyrene-equivalent molecular weight for the third generation was lower than for the second, although the same grafting density was obtained from (1)H NMR spectroscopy for the second and third generations. Tapping-mode atomic force microscopy was used to characterize the properties of the dendronized polymers in the dry state, exploring both the effect of the polar substrate mica and the less polar substrate highly oriented pyrolytic graphite (HOPG). It was found that the molecules were in the size range of tens of nanometers and that they were apt to undertake a more elongated conformation on the HOPG surfaces when long alkyl chains were attached as the dendron end-groups.     

Cerebral gene expression and neurobehavioural development after perinatal exposure to an environmentally relevant polybrominated diphenylether (BDE47)

Nutrients in seafood are known to be beneficial for brain development. Effects of maternal exposure to 2,2′,4,4′ tetrabromo diphenylether (BDE47) was investigated, alongside the potential ameliorating impact of seafood nutrients, through assessment of neurobehaviour and gene expression in brain and liver. Developing mice were exposed during gestation and lactation via dams dosed through casein- or salmon-based feed, spiked with BDE47. Two concentrations were used: a low level (6 μg/kg feed) representing an environmentally realistic concentration and a high level (1,900 μg/kg feed) representing a BDE47 intake much higher than expected from frequents consumption of contaminated seafood. Experimental groups were similar with respect to reproductive success, growth and physical development. Minor, transient changes in neurobehavioural metrics were observed in groups given the highest dose of BDE47. No significant differences in behaviour or development were seen on postnatal day 18 among maternally exposed offspring. Cerebral gene expression investigated by microarray analyses and validated by RT-qPCR showed low fold changes for all genes, despite dose-dependent accumulation of BDE47 in brain tissue. The gene for glutamate ammonia ligase was upregulated compared to control in the casein-based high BDE47diet, suggesting potential impacts on downstream synaptic transmission. The study supported a previously observed regulation of Igfbp2 in brain with BDE47 exposure. Genes for hepatic metabolic enzymes were not influenced by BDE47. Potential neurotoxic effects and neurobehavioural aberrations after perinatal exposure to high levels of BDE47 were not readily observed in mice pups with the present experimental exposure regimes and methods of analysis.     

Discovery of N-(1-adamantyl)-2-(4-alkylpiperazin-1-yl)acetamide derivatives as T-type calcium channel (Cav3.2) inhibitors

Chemical evolution of a HTS-based fragment hit resulted in the identification of N-(1-adamantyl)-2-[4-(2-tetrahydropyran-4-ylethyl)piperazin-1-yl]acetamide, a novel, selective T-type calcium channel (Ca(v)3.2) inhibitor with in vivo antihypertensive effect in rats.     

Early changes in bone mineral density measured by digital X-ray radiogrammetry predict up to 20 years radiological outcome in rheumatoid arthritis

Introduction  

Changes in bone mineral density (BMD) in the hand as evaluated by digital X-ray radiogrammetry (DXR) of the second to fourth metacarpal bones has been suggested to predict future joint damage in patients with rheumatoid arthritis (RA). This study's objective was to investigate whether DXR-BMD loss early in the course of the disease predicts the development of joint damage in RA patients followed for up to 20 years.     

Pericytes: developmental, physiological, and pathological perspectives, problems, and promises

Pericytes, the mural cells of blood microvessels, have recently come into focus as regulators of vascular morphogenesis and function during development, cardiovascular homeostasis, and disease. Pericytes are implicated in the development of diabetic retinopathy and tissue fibrosis, and they are potential stromal targets for cancer therapy. Some pericytes are probably mesenchymal stem or progenitor cells, which give rise to adipocytes, cartilage, bone, and muscle. However, there is still confusion about the identity, ontogeny, and progeny of pericytes. Here, we review the history of these investigations, indicate emerging concepts, and point out problems and promise in the field of pericyte biology.     

Surrogate antigens as targets for proteome-wide binder selection

In the past decade, many initiatives were taken for the development of antibodies for proteome-wide studies, as well as characterisation and validation of clinically relevant disease biomarkers. Phage display offers many advantages compared to antibody generation by immunisation because it is an unlimited resource of affinity reagents without batch-to-batch variation and is also amendable for high throughput in contrast to conventional hybridoma technology. One of the major bottlenecks to proteome-wide binder selection is the limited supply of suitable target antigens representative of the human proteome. Here, we provide proof of principle of using easily accessible, cancer-associated protein epitope signature tags (PrESTs), routinely generated within the Human Protein Atlas project, as surrogate antigens for full-length proteins in phage selections for the retrieval of target-specific binders. These binders were subsequently tested in western blot, immunohistochemistry and protein microarray application to demonstrate their functionality.     

Temperature and resource availability may interactively affect over-wintering success of juvenile fish in a changing climate

The predicted global warming may affect freshwater systems at several organizational levels, from organism to ecosystem. Specifically, in temperate regions, the projected increase of winter temperatures may have important effects on the over-winter biology of a range of organisms and especially for fish and other ectothermic animals. However, temperature effects on organisms may be directed strongly by resource availability. Here, we investigated whether over-winter loss of biomass and lipid content of juvenile roach (Rutilus rutilus) was affected by the physiologically relatively small (2-5 °C) changes of winter temperatures predicted by the Intergovernmental Panel on Climate Change (IPCC), under both natural and experimental conditions. This was investigated in combination with the effects of food availability. Finally, we explored the potential for a correlation between lake temperature and resource levels for planktivorous fish, i.e., zooplankton biomass, during five consecutive winters in a south Swedish lake. We show that small increases in temperature (+2 °C) affected fish biomass loss in both presence and absence of food, but negatively and positively respectively. Temperature alone explained only a minor part of the variation when food availability was not taken into account. In contrast to other studies, lipid analyses of experimental fish suggest that critical somatic condition rather than critical lipid content determined starvation induced mortality. Our results illustrate the importance of considering not only changes in temperature when predicting organism response to climate change but also food-web interactions, such as resource availability and predation. However, as exemplified by our finding that zooplankton over-winter biomass in the lake was not related to over-winter temperature, this may not be a straightforward task.     

Predator-induced morphological plasticity across local populations of a freshwater snail

The expression of anti-predator adaptations may vary on a spatial scale, favouring traits that are advantageous in a given predation regime. Besides, evolution of different developmental strategies depends to a large extent on the grain of the environment and may result in locally canalized adaptations or, alternatively, the evolution of phenotypic plasticity as different predation regimes may vary across habitats. We investigated the potential for predator-driven variability in shell morphology in a freshwater snail, Radix balthica, and whether found differences were a specialized ecotype adaptation or a result of phenotypic plasticity. Shell shape was quantified in snails from geographically separated pond populations with and without molluscivorous fish. Subsequently, in a common garden experiment we investigated reaction norms of snails from populations' with/without fish when exposed to chemical cues from tench (Tinca tinca), a molluscivorous fish. We found that snails from fish-free ponds had a narrow shell with a well developed spire, whereas snails that coexisted with fish had more rotund shells with a low spire, a shell morphology known to increase survival rate from shell-crushing predators. The common garden experiment mirrored the results from the field survey and showed that snails had similar reaction norms in response to chemical predator cues, i.e. the expression of shell shape was independent of population origin. Finally, we found significant differences for the trait means among populations, within each pond category (fish/fish free), suggesting a genetic component in the determination of shell morphology that has evolved independently across ponds.