The outcome of an automated assessment of trabecular pattern in intraoral radiographs as a fracture risk predictor

Objectives: This study aims to investigate if automated analyses of the trabecular pattern in intraoral radiographs independently contribute to fracture risk assessment when other risk factors incorporated in the Fracture Risk Assessment Tool (FRAX) are taken into account. A secondary aim is to explore the correlation between the automated trabecular pattern assessment in intraoral radiographs and Trabecular Bone Score (TBS). Methods: A total of 567 intraoral radiographs from older females participating in a large population-based study (SUPERB) based in Gothenburg, Sweden, were selected to analyse trabecular pattern using semi-automated and fully automated software. Associations between trabecular pattern analysis and incident fractures were studied using Cox proportional hazard model, unadjusted and adjusted for FRAX risk factors (previous fracture, family history of hip fracture, smoking, corticosteroids, rheumatoid arthritis, without and with bone mineral density (BMD) of the femoral neck). In addition, the correlation between trabecular pattern analysis and TBS of the lumbar spine was investigated using Pearson correlation analysis. Results: Neither the unadjusted nor the adjusted trabecular pattern analysis in intraoral radiographs was significantly associated with any fracture or major osteoporotic fracture (MOF). A weak correlation was found between semi-automated trabecular pattern analysis and TBS. No correlation was found between the fully automated trabecular pattern analysis and TBS. Conclusions: The present study shows that semi-automated and fully automated digital analyses of the trabecular pattern in intraoral radiographs do not contribute to fracture risk prediction. Furthermore, the study shows a weak correlation between semi-automated trabecular pattern analysis and TBS

Stromal integrin α11 regulates PDGFRβ signaling and promotes breast cancer progression

Cancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors, such as breast cancer (BC). Herein, we identify an integrin alpha 11/PDGFR beta-positive CAF subset displaying tumor-promoting features in BC. In the preclinical MMTV-PyMT mouse model, integrin alpha 11 deficiency led to a drastic reduction of tumor progression and metastasis. A clear association between integrin alpha 11 and PDGFR beta was found at both transcriptional and histological levels in BC specimens. High stromal integrin alpha 11/PDGFR beta expression was associated with high grades and poorer clinical outcome in human BC patients. Functional assays using 5 CAF subpopulations (1 murine, 4 human) revealed that integrin alpha 11 promotes CAF invasion and CAF-induced tumor cell invasion upon PDGF-BB stimulation. Mechanistically, the proinvasive activity of integrin alpha 11 relies on its ability to interact with PDGFR beta in a ligand-dependent manner and to promote its downstream JNK activation, leading to the production of tenascin C, a proinvasive matricellular protein. Pharmacological inhibition of PDGFR beta and JNK impaired tumor cell invasion induced by integrin alpha 11 CAFs. Collectively, our study uncovers an integrin alpha 11 subset of protumoral CAFs that exploits the PDGFR beta/JNK signaling axis to promote tumor invasiveness in BC

UV-Deprived Coloration Reduces Success in Mate Acquisition in Male Sand Lizards (Lacerta agilis)

Background: Recent work on animal signals has revealed a wide occurrence of UV signals in tetrapods, in particular birds, but also in lizards (and perhaps other Squamate reptiles). Our previous work on the Swedish sand lizard (Lacerta agilis) has verified, both in correlative selection analyses in the wild and with laboratory and field experiments, the importance of the green ‘badge ’ on the body sides of adult males for securing mating opportunities, probably mostly through deterring rival males rather than attracting females. The role of UV in communication has, however, never been examined. Methodology/Principal Findings: Here we show that when measured immediately after spring skin shedding, there is also signaling in the UV. By UV-depriving the signal (reflectance) with sun block chemicals fixated with permeable, harmless spray dressing, we show that males in the control group (spray dressing only) had significantly higher success in mate acquisition than UV-deprived males. Conclusions/Significance: These results suggest that at least two colour traits in sand lizards, badge area and UV, contribute to rival deterrence and/or female choice on UV characters, which elevates success in mate acquisition in UV intact male sand lizards

Selection of Resistant Bacteria at Very Low Antibiotic Concentrations

The widespread use of antibiotics is selecting for a variety of resistance mechanisms that seriously challenge our ability to treat bacterial infections. Resistant bacteria can be selected at the high concentrations of antibiotics used therapeutically, but what role the much lower antibiotic concentrations present in many environments plays in selection remains largely unclear. Here we show using highly sensitive competition experiments that selection of resistant bacteria occurs at extremely low antibiotic concentrations. Thus, for three clinically important antibiotics, drug concentrations up to several hundred-fold below the minimal inhibitory concentration of susceptible bacteria could enrich for resistant bacteria, even when present at a very low initial fraction. We also show that de novo mutants can be selected at sub-MIC concentrations of antibiotics, and we provide a mathematical model predicting how rapidly such mutants would take over in a susceptible population. These results add another dimension to the evolution of resistance and suggest that the low antibiotic concentrations found in many natural environments are important for enrichment and maintenance of resistance in bacterial populations

Construction of a system for heterologous production of carbonic anhydrase from Plasmodium falciparum in Pichia pastoris

Malaria is one of the biggest current global health problems, and with the increasing occurance of drug resistant Plasmodium falciparum strains, there is an urgent need for new antimalarial drugs. Given the important role of carbonic anhydrase in Plasmodium falciparum (PfCA), it is a potential novel drug target. Heterologous expression of malaria proteins is problematic due to the unusual codon usage of the Plasmodium genome, so to overcome this problem a synthetic PfCA gene was designed, optimized for expression in Pichia pastoris. This gene was also modified to avoid glycosylation, and cloned into the vector pPICZαA under the control of the methanol inducible promoter AOX1. To facilitate export of the protein into the growth medium, the gene was fused in-frame with the α-factor secretion signal from Saccharomyces cerevisiae. The construct was successfully integrated in the genome of P. pastoris GS115, and attempts were made to express the protein and purify it using immobilized metal ion affinity chromatography.In this work, no expression of the PfCA protein could be detected, so further research should focus on optimization of expression conditions, or redesign of the expression vector

Selection of Resistance at very low Antibiotic Concentrations

The extensive medical and agricultural use and misuse of antibiotics during the last 70 years has caused an enrichment of resistant pathogenic bacteria that now severely threatens our capacity to efficiently treat bacterial infections. While is has been known for a long time that high concentrations of antibiotics can select for resistant mutants, less is known about the lower limit at which antibiotics can be selective and enrich for resistant bacteria. In this thesis we investigated the role of low concentrations of antibiotics and heavy metals in the enrichment and evolution of antibiotic resistance. Selection was studied using Escherichia coli and Salmonella enterica serovar Typhimurium LT2 with different resistance mutations, different chromosomal resistance genes as well as large conjugative multidrug resistance plasmids. Using very sensitive competition experiments, we showed that antibiotic and heavy metal levels more than several hundred-fold below the minimal inhibitory concentration of susceptible bacteria can enrich for resistant bacteria. Additionally, we demonstrated that subinhibitory levels of antibiotics can select for de novo resistant mutants, and that these conditions can select for a new spectrum of low-cost resistance mutations. The combinatorial effects of antibiotics and heavy metals can cause an enrichment of a multidrug resistance plasmid, even if the concentration of each compound individually is not high enough to cause selection. These results indicate that environments contaminated with low levels of antibiotics and heavy metals such as, for example, sewage water or soil fertilized with sludge or manure, could provide a setting for selection, enrichment and transfer of antibiotic resistance genes. This selection could be a critical step in the transfer of resistance genes from environmental bacteria to human pathogens

Market Designs : A Survey and Analysis of Methods to Ensure Peak Capacity

The production and consumption of electricity must be in balance in order to maintain the frequency in an electrical grid. During peak loads this may be troublesome to achieve due to lack of adequate production capabilities. Competitive electricity markets with price caps have a problem - insufficient revenues for peak production units which lead to mothballing or decommissioning of power plants. Inadequate production capability is solved through design of the electricity markets which renders in incentives to operate these power plants. This report analyzes the most common market designs with the Nordic countries of Finland, Norway, and Sweden in mind. The Nordic situation is used as the background for an evaluation of the impact of the chosen designs. The question of finding a market solution of the peak load problem is yet a prerequisite. The conclusions are that a clear definition of what a market solution is, is needed in order to determine which design to prefer. The view on what to address as the problem makes a difference - treating the symptoms or the root causes leads to usage of different market designs as solutions. The Nordic countries may be better off by waiting to see the effects of the full penetration of the Automatic Meter Reading systems, which may reduce the peak loads by increasing the demand responsiveness. The current market designs in the Nordic countries may also be sufficient while developing the market's demand response, and thereby not call for implementations of other market designs

Market Designs : A Survey and Analysis of Methods to Ensure Peak Capacity

The production and consumption of electricity must be in balance in order to maintain the frequency in an electrical grid. During peak loads this may be troublesome to achieve due to lack of adequate production capabilities. Competitive electricity markets with price caps have a problem - insufficient revenues for peak production units which lead to mothballing or decommissioning of power plants. Inadequate production capability is solved through design of the electricity markets which renders in incentives to operate these power plants. This report analyzes the most common market designs with the Nordic countries of Finland, Norway, and Sweden in mind. The Nordic situation is used as the background for an evaluation of the impact of the chosen designs. The question of finding a market solution of the peak load problem is yet a prerequisite. The conclusions are that a clear definition of what a market solution is, is needed in order to determine which design to prefer. The view on what to address as the problem makes a difference - treating the symptoms or the root causes leads to usage of different market designs as solutions. The Nordic countries may be better off by waiting to see the effects of the full penetration of the Automatic Meter Reading systems, which may reduce the peak loads by increasing the demand responsiveness. The current market designs in the Nordic countries may also be sufficient while developing the market's demand response, and thereby not call for implementations of other market designs