eNOS Activation by HDL Is Impaired in Genetic CETP Deficiency

Mutations in the CETP gene resulting in defective CETP activity have been shown to cause remarkable elevations of plasma HDL-C levels, with the accumulation in plasma of large, buoyant HDL particles enriched in apolipoprotein E. Genetic CETP deficiency thus represents a unique tool to evaluate how structural alterations of HDL impact on HDL atheroprotective functions. Aim of the present study was to assess the ability of HDL obtained from CETP-deficient subjects to protect endothelial cells from the development of endothelial dysfunction. HDL isolated from one homozygous and seven heterozygous carriers of CETP null mutations were evaluated for their ability to down-regulate cytokine-induced cell adhesion molecule expression and to promote NO production in cultured endothelial cells. When compared at the same protein concentration, HDL and HDL3 from carriers proved to be as effective as control HDL and HDL3 in down-regulating cytokine-induced VCAM-1, while carrier HDL2 were more effective than control HDL2 in inhibiting VCAM-1 expression. On the other hand, HDL and HDL fractions from carriers of CETP deficiency were significantly less effective than control HDL and HDL fractions in stimulating NO production, due to a reduced eNOS activating capacity, likely because of a reduced S1P content. In conclusion, the present findings support the notion that genetic CETP deficiency, by affecting HDL particle structure, impacts on HDL vasculoprotective functions. Understanding of these effects might be important for predicting the outcomes of pharmacological CETP inhibition.     

A Multiresolution Approach to Discrete Tomography Using DART

In discrete tomography, a scanned object is assumed to consist of only a few different materials. This prior knowledge can be effectively exploited by a specialized discrete reconstruction algorithm such as the Discrete Algebraic Reconstruction Technique (DART), which is capable of providing more accurate reconstructions from limited data compared to conventional reconstruction algorithms. However, like most iterative reconstruction algorithms, DART suffers from long computation times. To increase the computational efficiency as well as the reconstruction quality of DART, a multiresolution version of DART (MDART) is proposed, in which the reconstruction starts on a coarse grid with big pixel (voxel) size. The resulting reconstruction is then resampled on a finer grid and used as an initial point for a subsequent DART reconstruction. This process continues until the target pixel size is reached. Experiments show that MDART can provide a significant speed-up, reduce missing wedge artefacts and improve feature reconstruction in the object compared with DART within the same time, making its use with large datasets more feasible.     

Effects of multiple global change treatments on soil N2O fluxes

Global environmental changes are expected to alter ecosystem carbon and nitrogen cycling, but the interactive effects of multiple simultaneous environmental changes are poorly understood. Effects of these changes on the production of nitrous oxide (N₂O), an important greenhouse gas, could accelerate climate change. We assessed the responses of soil N₂O fluxes to elevated CO₂, heat, altered precipitation, and enhanced nitrogen deposition, as well as their interactions, in an annual grassland at the Jasper Ridge Global Change Experiment (CA, USA). Measurements were conducted after 6, 7 and 8?years of treatments. Elevated precipitation increased N₂O efflux, especially in combination with added nitrogen and heat. Path analysis supported the idea that increased denitrification due to increased soil water content and higher labile carbon availability best explained increased N₂O efflux, with a smaller, indirect contribution from nitrification. In our data and across the literature, single-factor responses tended to overestimate interactive responses, except when global change was combined with disturbance by fire, in which case interactive effects were large. Thus, for chronic global environmental changes, higher order interactions dampened responses of N₂O efflux to multiple global environmental changes, but interactions were strongly positive when global change was combined with disturbance. Testing whether these responses are general should be a high priority for future research.     

The valve movement response of mussels: a tool in biological monitoring

Biological sensors are becoming more important to monitor the quality of the aquatic environment. In this paper the valve movement response of freshwater (Dreissena polymorpha) and marine (Mytilus edulis) mussels is presented as a tool in monitoring studies. Examples of various methods for data storage and data treatment are presented, elucidating easier operation and lower detection limits. Several applications are mentioned, including an early warning system based on this valve movement response of mussels.     

Simultaneous immunization against tuberculosis

Background

BCG, the only licensed vaccine against tuberculosis, provides some protection against disseminated disease in infants but has little effect on prevention of adult pulmonary disease. Newer parenteral immunization prime boost regimes may provide improved protection in experimental animal models but are unproven in man so that there remains a need for new and improved immunization strategies.

Methods and Findings

Mice were immunized parenterally, intranasally or simultaneously by both routes with BCG or recombinant mycobacterial antigens plus appropriate adjuvants. They were challenged with Mycobacterium tuberculosis (Mtb) and the kinetics of Mtb growth in the lungs measured. We show that simultaneous immunization (SIM) of mice by the intranasal and parenteral routes is highly effective in increasing protection over parenteral BCG administration alone. Intranasal immunization induces local pulmonary immunity capable of inhibiting the growth of Mtb in the early phase (the first week) of infection, while parenteral immunization has a later effect on Mtb growth. Importantly, these two effects are additive and do not depend on priming and boosting the immune response. The best SIM regimes reduce lung Mtb load by up to 2 logs more than BCG given by either route alone.

Conclusions

These data establish SIM as a novel and highly effective immunization strategy for Mtb that could be carried out at a single clinic visit. The efficacy of SIM does not depend on priming and boosting an immune response, but SIM is complementary to prime boost strategies and might be combined with them.     

Pictorial key to species of the genus Ropalidia Guérin-Méneville, 1831 (Hymenoptera,Vespidae) from China,with description of one new species

Twenty two species of the paper wasp genus Ropalidia Guérin-Méneville, 1831, are listed from China. Among them, R. malaisei van der Vecht, 1962, R. cyathiformis (Fabricius, 1804), R. santoshae Das & Gupta, 1989, R. scitula (Bingham, 1897), R. obscura Gusenleitner, 1996 and R. ornaticeps (Cameron, 1900) are new records from China. A new species, R. parartifex Tan & van Achterberg, is described. Their diagnostic characteristics are summarized in an illustrated key and 36 colourplates.     

Biostratigraphy or biochronology? Lessons from the Early and Middle Miocene small Mammal Events in Europe

Since the proposition in 1975 of the European Neogene Mammal (MN) scale by Pierre Mein, the amount of taxonomical, stratigraphical and chronological information around Europe has increased exponentially. In this paper, the stratigraphical schemes of three of the best studied areas for the Lower and Middle Miocene, the Aragonian type area in Spain and the Upper Freshwater Molasse from the North Alpine Foreland Basin in Switzerland and Bavaria, are compared. The correlation of their local biostratigraphies are discussed. Sixteen rodent's events are studied and ranked in the three areas according to their local biostratigraphy. This study shows, and quantifies for the first time, the significant asynchronies of the different included rodent events. The MN-system is discussed in the light of those results. In accordance, we propose that it is still useful but only in a biochronological way, as a sequence of time-ordered reference localities allowing coarse long-distance correlations. In order to obtain better temporal resolution, this system has to be combined with local biostratigraphies that are well calibrated to the time scale, implementing the information about synchrony and diachrony of mammal events in different areas.     

De taalbarrière bij oudere Turkse vrouwen nader onderzocht

A growing group of migrants age in an environment in which the dominant language (L2) differs from their mother tongue (L1). This study considers the occurrence of a language barrier in accessing (information on) health and healthcare provisions, and under which circumstances a limited proficiency in the L2 negatively influences well-being for a group of older Turkish women in the Netherlands. Data from interviews with 39 Turkish females reveal that a limited L2 proficiency does not automatically result in a lower level of well-being. When individuals are well-embedded in a social network (and feel belonging to it), a limited L2 proficiency can be alleviated by either L1 assistance from their environment or by facilitating an interpreter in L2 situations. However, when such a network is absent, L2 situations can cause anxiety, which may have repercussions for well-being. Even though there is no clear one-on-one relationship between language and well-being, language does play a role in many (social) processes that influence well-being.     

Model‐driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation

The abundance of the human intestinal symbiont Akkermansia muciniphila has found to be inversely correlated with several diseases, including metabolic syndrome and obesity. A. muciniphila is known to use mucin as sole carbon and nitrogen source. To study the physiology and the potential for therapeutic applications of this bacterium, we designed a defined minimal medium. The composition of the medium was based on the genome‐scale metabolic model of A. muciniphila and the composition of mucin. Our results indicate that A. muciniphila does not code for GlmS, the enzyme that mediates the conversion of fructose‐6‐phosphate (Fru6P) to glucosamine‐6‐phosphate (GlcN6P), which is essential in peptidoglycan formation. The only annotated enzyme that could mediate this conversion is Amuc‐NagB on locus Amuc_1822. We found that Amuc‐NagB was unable to form GlcN6P from Fru6P at physiological conditions, while it efficiently catalyzed the reverse reaction. To overcome this inability, N‐acetylglucosamine needs to be present in the medium for A. muciniphila growth. With these findings, the genome‐scale metabolic model was updated and used to accurately predict growth of A. muciniphila on synthetic media. The finding that A. muciniphila has a necessity for GlcNAc, which is present in mucin further prompts the adaptation to its mucosal niche.