Three-dimensional collagen regulates collagen gene expression by a mechanism that requires serine/threonine kinases and is independent of mechanical contraction

Integrin alpha1beta1, one of the cellular collagen receptors, can participate in the regulation of collagen accumulation by acting as a negative feedback regulator. The molecular mechanism behind this phenomenon has been unknown. We have plated cells inside three-dimensional collagen and analyzed a set of chemical inhibitors for various signal transduction pathways. Only two wide-spectrum serine/threonine kinase inhibitors, H-7 and iso-H-7 could prevent the down-regulation of alpha1(I) collagen mRNA levels in cells exposed to three-dimensional collagen. In monolayer iso-H-7 slightly down-regulated collagen gene expression, indicating that inside collagen it affected integrin signaling rather than having a direct stimulatory effect on collagen mRNA levels. The effect of iso-H-7 was not dependent on its ability to inhibit protein kinases A, C, or G. H-7 and iso-H-7 could also inhibit collagen gel contraction, but this mechanism was independent of collagen gene regulation. Three-dimensional collagen could also up-regulate the mRNA levels of several matrix metalloproteinases (MMPs) but H-7 and iso-H-7 had no effect on the regulation of MMP genes. Our data indicate that three-dimensional collagenous matrix regulates distinct cellular signaling pathways and that collagen gene regulation is independent of the other effects of the matrix.     

Decline in mortality from coronary heart disease in Finland from 1969 to 1979.

The trends in mortality from coronary heart disease in the 1970s and the differences in trends between counties within Finland were calculated from official mortality statistics among the population aged 35 to 64 years. During this period coronary mortality declined by a mean of 1.1% for men and 2.3% for women annually in the whole of Finland. A community based cardiovascular control programme was started in 1972 in North Karelia, a county in the east of Finland. The decline in coronary mortality in this county between 1969 and 1979 was 24% in men and 51% in women. The decline in the rest of Finland over the same period was 12% in men and 24% in women. The decline in North Karelia was greater than that in other counties of Finland for both men and women and that difference exceeded random variation, with over 95% likelihood for both sexes. Even with adjustment for rates before 1974 with cross-county multiple regression analyses the difference persisted. Although further studies are needed, the changes in coronary mortality in North Karelia suggest that the preventive programme has been effective.     

Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player

Molecular Biology Reports - Little is known about the signaling pathways involved in the differentiation of human osteoclasts. The present study evaluated the roles of the Ras/PI3K/Akt/mTOR,...     

Existence of natural mouse IgG mAbs recognising epitopes shared by malondialdehyde acetaldehyde adducts and Porphyromonas gingivalis

Natural Abs are produced by B lymphocytes in the absence of external Ag stimulation. They recognise self, altered self and foreign Ags, comprising an important first-line defence against invading pathogens and serving as innate recognition receptors for tissue homeostasis. Natural IgG Abs have been found in newborns and uninfected individuals. Yet, their physiological role remains unclear. Previously, no natural IgG Abs to oxidation-specific epitopes have been reported. Here, we show the cloning and characterisation of mouse IgG mAbs against malondialdehyde acetaldehyde (MAA)-modified low-density lipoprotein. Sequence analysis reveals high homology with germline genes, suggesting that they are natural. Further investigation shows that the MAA-specific natural IgG Abs cross-react with the major periodontal pathogen Porphyromonas gingivalis and recognise its principle virulence factors gingipain Kgp and long fimbriae. The study provides evidence that natural IgGs may play an important role in innate immune defence and in regulation of tissue homeostasis by recognising and removing invading pathogens and/or modified self-Ags, thus being involved in the development of periodontitis and atherosclerosis.     

Biogenic nanoporous silicon carrier improves the efficacy of buparvaquone against resistant visceral leishmaniasis

Visceral leishmaniasis is a vector-borne protozoan infection that is fatal if untreated. There is no vaccination against the disease, and the current chemotherapeutic agents are ineffective due to increased resistance and severe side effects. Buparvaquone is a potential drug against the leishmaniases, but it is highly hydrophobic resulting in poor bioavailability and low therapeutic efficacy. Herein, we loaded the drug into silicon nanoparticles produced from barley husk, which is an agricultural residue and widely available. The buparvaquone-loaded nanoparticles were several times more selective to kill the intracellular parasites being non-toxic to macrophages compared to the pure buparvaquone and other conventionally used anti-leishmanial agents. Furthermore, the in vivo results revealed that the intraperitoneally injected buparvaquone-loaded nanoparticles suppressed the parasite burden close to 100%. By contrast, pure buparvaquone suppressed the burden only by 50% with corresponding doses. As the conclusion, the biogenic silicon nanoparticles are promising carriers to significantly improve the therapeutic efficacy and selectivity of buparvaquone against resistant visceral leishmaniasis opening a new avenue for low-cost treatment against this neglected tropical disease threatening especially the poor people in developing nations.     

Culture-independent molecular approaches reveal a mostly unknown high diversity of active nitrogen-fixing bacteria associated with Pennisetum purpureum—a bioenergy crop

Aims

Previous studies have shown that elephant grass is colonized by nitrogen-fixing bacterial species; however, these results were based on culture-dependent methods, an approach that introduces bias due to an incomplete assessment of the microbial community. In this study, we used culture-independent methods to survey the diversity of endophytes and plant-associated bacterial communities in five elephant grass genotypes used in bioenergy production.

Methods

The plants of five genotypes of elephant grass were harvested from the experimental area of Embrapa Agrobiologia and divided into stem and root tissues. Total DNA and RNA were extracted from plant tissues and the bacterial communities were analyzed by DGGE and clone library of the 16S rRNA and nifH genes at both the cDNA and DNA levels.

Results

Overall, the patterns based on DNA- and RNA-derived DGGE-profiles differed, especially within tissue samples. DNA-based DGGE indicated that both total bacterial and diazotrophic communities associated with roots (rhizoplane?+?endophytes) differed clearly from those obtained from stems (endophytes). These results were confirmed by the phylogenetic analyses of RNA-derived sequences of 16S rRNA (total bacteria; 586 sequences), but not for nifH (186). In fact, rarefaction analyses showed a higher diversity of diazotrophic organisms associated with stems than roots. Based on 16S rRNA sequences, the clone libraries were dominated by sequences affiliated to members of Leptotrix (12.8 %) followed by Burkholderia (9 %) and Bradyrhizobium (6.5 %), while most of the nifH clones were closely related to the genus Bradyrhizobium (26 %).

Conclusions

Our results revealed an unexpectedly large diversity of metabolically active bacteria, providing new insights into the bacterial species predominantly found in association with elephant grass. Furthermore, these results can be very useful for the development of new strategies for selection of potential bacteria that effectively contribute to biological nitrogen fixation and enhance the sustainable production of elephant grass as bioenergy crop.     

Erratum to: Gene expression profiling in the submandibular gland,stomach, and duodenum of CAVI-deficient mice

Transgenic Research -     

Methodological Aspects of Applying Life Cycle Assessment to Industrial Symbioses

In view of recent studies of the historical development and current status of industrial symbiosis (IS), life cycle assessment (LCA) is proposed as a general framework for quantifying the environmental performance of by‐product exchange. Recent guidelines for LCA (International Reference Life Cycle Data System [ILCD] guidelines) are applied to answer the main research questions in the IS literature reviewed. A typology of five main research questions is proposed: (1) analysis, (2) improvement, and (3) expansion of existing systems; (4) design of new eco‐industrial parks, and (5) restructuring of circular economies. The LCA guidelines were found useful in framing the question and choosing an appropriate reference case for comparison. The selection of a correct reference case reduces the risk of overestimating the benefits of by‐product exchange. In the analysis of existing systems, environmentally extended input‐output analysis (EEIOA) can be used to streamline the analysis and provide an industry average baseline for comparison. However, when large‐scale changes are applied to the system, more sophisticated tools are necessary for assessment of the consequences, from market analysis to general equilibrium modeling and future scenario work. Such a rigorous application of systems analysis was not found in the current IS literature, but would benefit the field substantially, especially when the environmental impact of large‐scale economic changes is analyzed.