Analysis of the dorsal-ventral gene regulatory network of Nasonia vitripennis

Analysis of the DV axis of Nasonia revealed that all investigated Toll pathway components and most zygotically expressed DV patterning genes known from Drosophila are also present in the Nasonia genome. Prior to gastrulation, gene expression is quite similar when compared to Drosophila. However, regulation of gene expression is more dynamic. The functional analysis revealed a conserved role for Toll signaling in embryonic DV axis polarization. However, in contrast to Drosophila, Toll’s function in providing pattern information is reduced to the formation of ventral fates in Nasonia. Additionally, it seems that Toll signaling does not result in a broad stable gradient of nuclear Dorsal. It induces a narrow domain of zygotic gene expression that dynamically expands independent of Toll signaling. Furthermore, the Drosophila Toll signaling target gene sog, which is essential for the formation of the dorsal BMP gradient is absent in Nasonia. Nevertheless, peak levels of BMP signaling along the dorsal midline are established and even obtained in the absence of Toll signaling in Nasonia. This suggests, that the Nasonia DV axis is established by bipolar signal induction from both the ventral and the dorsal side, which is in contrast to the unipolar Toll dependent axis determination observed in Drosophila. Moreover, the functional analysis of the GRN provides strong evidence for the assumption that BMP signaling plays the dominant role in providing DV polarity in the early embryo of Nasonia. To investigate the influence of the BMP and Toll pathway on early embryogenesis in an unbiased way, a transcriptome analysis was performed. The generated transcriptome data set provides an optimal tool to investigate genes that are putative downstream targets of Toll and BMP signaling. A preliminary screen based on a high throughput variant of ISH already discovered previously described Drosophila orthologs as well as unknown hymenoptera specific genes that hold a potentially important role in the DV GRN of Nasonia

EurA1c: the European HbA1c Trial to Investigate the Performance of HbA1c Assays in 2166 Laboratories across 17 Countries and 24 Manufacturers by Use of the IFCC Model for Quality Targets

Background: A major objective of the IFCC Committee on Education and Use of Biomarkers in Diabetes is to generate awareness and improvement of HbA1c assays through evaluation of the performance by countries and manufacturers. Methods: Fresh whole blood and lyophilized hemolysate specimens manufactured from the same pool were used by 17 external quality assessment organizers to evaluate analytical performance of 2166 laboratories. Results were evaluated per country, per manufacturer, and per manufacturer and country combined according to criteria of the IFCC model for quality targets. Results: At the country level with fresh whole blood specimens, 6 countries met the IFCC criterion, 2 did not, and 2 were borderline. With lyophilized hemolysates, 5 countries met the criterion, 2 did not, and 3 were borderline. At the manufacturer level using fresh whole blood specimens, 13 manufacturers met the criterion, 8 did not, and 3 were borderline. Using lyophilized hemolysates, 7 manufacturers met the criterion, 6 did not, and 3 were borderline. In both country and manufacturer groups, the major contribution to total error derived from between-laboratory variation. There were no substantial differences in performance between groups using fresh whole blood or lyophilized hemolysate samples. Conclusions: The state of the art is that 1 of 20 laboratories does not meet the IFCC criterion, but there are substantial differences between country and between manufacturer groups. Efforts to further improve quality should focus on reducing between-laboratory variation. With some limitations, fresh whole blood and well-defined lyophilized specimens are suitable for purpose

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Ancient and diverged TGF-β signaling components in Nasonia vitripennis

The transforming growth factor beta (TGF)-β signaling pathway and its modulators are involved in many aspects of cellular growth and differentiation in all metazoa. Although most of the core components of the pathway are highly conserved, many lineage-specific adaptations have been observed including changes regarding paralog number, presence and absence of modulators, and functional relevance for particular processes. In the parasitic jewel wasp Nasonia vitripennis, the bone morphogenetic proteins (BMPs), one of the major subgroups of the TGF-β superfamily, play a more fundamental role in dorsoventral (DV) patterning than in all other insects studied so far. However, Nasonia lacks the BMP antagonist Short gastrulation (Sog)/chordin, which is essential for polarizing the BMP gradient along the DV axis in most bilaterian animals. Here, we present a broad survey of TGF-β signaling in Nasonia with the aim to detect other lineage-specific peculiarities and to identify potential mechanisms, which explain how BMP-dependent DV pattering occurs in the early Nasonia embryo in the absence of Sog. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00427-014-0481-0) contains supplementary material, which is available to authorized users

Dorsoventral Polarity of the Nasonia Embryo Primarily Relies on a BMP Gradient Formed without Input from Toll

SummaryIn Drosophila, Toll signaling leads to a gradient of nuclear uptake of Dorsal with a peak at the ventral egg pole and is the source for dorsoventral (DV) patterning and polarity of the embryo [1–3]. In contrast, Toll signaling plays no role in embryonic patterning in most animals [4, 5], while BMP signaling plays the major role [6]. In order to understand the origin of the novelty of the Drosophila system, we have examined DV patterning in Nasonia vitripennis (Nv) [7], a representative of the Hymenoptera and thus the most ancient branch points within the Holometabola [8]. We have previously shown that while the expression of several conserved DV patterning genes is almost identical in Nasonia and Drosophila embryos at the onset of gastrulation, the ways these patterns evolve in early embryogenesis are very different from what is seen in Drosophila [7] or the beetle Tribolium [9]. In contrast to Drosophila or Tribolium, we find that wasp Toll has a very limited ventral role, whereas BMP is required for almost all DV polarity of the embryo, and these two signaling systems act independently of each other to generate DV polarity. This result gives insights into how the Toll pathway could have usurped a BMP-based DV patterning system in insects. In addition, our work strongly suggests that a novel system for BMP activity gradient formation must be employed in the wasp, since orthologs of crucial components of the fly system are either missing entirely or lack function in the embryo