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.     

Role of the microtubule destabilizing proteins SCG10 and stathmin in neuronal growth

The related proteins SCG10 and stathmin are highly expressed in the developing nervous system. Recently it was discovered that they are potent microtubule destabilizing factors. While stathmin is expressed in a variety of cell types and shows a cytosolic distribution, SCG10 is neuron-specific and membrane-associated. It contains an N-terminal targeting sequence that mediates its transport to the growing tips of axons and dendrites. SCG10 accumulates in the central domain of the growth cone, a region that also contains highly dynamic microtubules. These dynamic microtubules are known to be important for growth cone advance and responses to guidance cues. Because overexpression of SCG10 strongly enhances neurite outgrowth, SCG10 appears to be an important factor for the dynamic assembly and disassembly of growth cone microtubules during axonal elongation. Phosphorylation negatively regulates the microtubule destabilizing activity of SCG10 and stathmin, suggesting that these proteins may link extracellular signals to the rearrangement of the neuronal cytoskeleton. A role for these proteins in axonal elongation is also supported by their growth-associated expression pattern in nervous system development as well as during neuronal regeneration.     

Wetlands serve as natural sources for improvement of stream ecosystem health in regions affected by acid deposition

For over 40 years, acid deposition has been recognized as a serious international environmental problem, but efforts to restore acidified streams and biota have had limited success. The need to better understand the effects of different sources of acidity on streams has become more pressing with the recent increases in surface water organic acids, or ‘brownification,’ associated with climate change and decreased inorganic acid deposition. Here, we carried out a large scale multi‐seasonal investigation in the Adirondacks, one of the most acid‐impacted regions in the United States, to assess how acid stream producers respond to local and watershed influences and whether these influences can be used in acidification remediation. We explored the pathways of wetland control on aluminum chemistry and diatom taxonomic and functional composition. We demonstrate that streams with larger watershed wetlands have higher organic content, lower concentrations of acidic anions, and lower ratios of inorganic to organic monomeric aluminum, all beneficial for diatom biodiversity and guilds producing high biomass. Although brownification has been viewed as a form of pollution, our results indicate that it may be a stimulating force for biofilm producers with potentially positive consequences for higher trophic levels. Our research also reveals that the mechanism of watershed control of local stream diatom biodiversity through wetland export of organic matter is universal in running waters, operating not only in hard streams, as previously reported, but also in acid streams. Our findings that the negative impacts of acid deposition on Adirondack stream chemistry and biota can be mitigated by wetlands have important implications for biodiversity conservation and stream ecosystem management. Future acidification research should focus on the potential for wetlands to improve stream ecosystem health in acid‐impacted regions and their direct use in stream restoration, for example, through stream rechanneling or wetland construction in appropriate hydrologic settings.     

Road exposure and the detectability of birds in field surveys

Road ecology, the study of the impacts of roads and their traffic on wildlife, including birds, is a rapidly growing field, with research showing effects on local avian population densities up to several kilometres from a road. However, in most studies, the effects of roads on the detectability of birds by surveyors are not accounted for. This could be a significant source of error in estimates of the impacts of roads on birds and could also affect other studies of bird populations. Using road density, traffic volume and bird count data from across Great Britain, we assess the relationships between roads and detectability of a range of bird species. Of 51 species analysed, the detectability of 36 was significantly associated with road exposure, in most cases inversely. Across the range of road exposure recorded for each species, the mean positive change in detectability was 52% and the mean negative change was 36%, with the strongest negative associations found in smaller-bodied species and those for which aural cues are more important in detection. These associations between road exposure and detectability could be caused by a reduction in surveyors’ abilities to hear birds or by changes in birds’ behaviour, making them harder or easier to detect. We suggest that future studies of the impacts of roads on populations of birds or other taxa, and other studies using survey data from road-exposed areas, should account for the potential impacts of roads on detectability.     

The expression of Galectin-3 in endometrial cancer: a systematic review of the literature

Molecular Biology Reports - Galectin-3 is part of a protein group called lectins and acts as a multifunctional glycoprotein due to its expression location. Galectin-3 is expressed by different...     

Social inequalities and mortality in europe - results from a large multi-national cohort

Background

Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans.

Methods

A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model''s with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality.

Results

Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52–0.61); among women by 29% (HR 0.71, 95% C.I. 0.64–0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries.

Discussion

In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.     

Viridin analogs derived from steroidal building blocks

Naturally occurring furanosteroids such as viridin and wortmannin have long been known as potent inhibitors of the lipid kinase PI-3K. We have been interested in directly accessing analogs of these complex natural products from abundant steroid feedstock materials. In this communication, we describe the synthesis of viridin/wortmannin hybrid molecules from readily available building blocks that function as PI-3K inhibitors and maintain their electrophilic properties. The compounds also show anti-proliferative effects against a breast cancer line.     

Hematopoietic differentiation of embryonic stem cells

This review is focused on methods that are used to derive hematopoietic cells from embryonic stem cells (ESCs). One of the strategies that have been recently used to achieve this goal is an approach of mimicking the hematopoietic niche in vitro by using hematopoiesis-supportive feeder cells, cocktails of soluble hematopoietic growth factors and a variety of matrices. While there is clear evidence that it is possible to derive hematopoietic stem cells (HSCs) and subsequently committed hematopoietic progenitors and mature cells from ESCs, there remains the need to address multiple issues including the efficiency of HSCs derivation in vitro and their proper functionality.     

Fas is not essential for lamina propria T lymphocyte homeostasis

IL-2 receptor alpha-deficient (IL2Ralpha-/-) mice spontaneously accumulate vast numbers of intestinal lamina propria (LP) T cells and develop bowel inflammation. The accumulation of T cells in IL2Ralpha-/- mice is thought to result, in part, from defective Fas-induced cell death. To understand the role of cell proliferation and death in regulating LP T cells in IL2Ralpha-/- mice, we have directly examined the proliferation and Fas sensitivity of wild-type, lpr/lpr, and IL2Ralpha-/- LP T cells. In wild-type mice, 5'-bromodeoxyuridine (BrdU) labeling and Fas susceptibility are greatest in CD44Hi LP T cells. Fas-deficient lpr/lpr mice have normal total numbers of LP T cells, despite an increased proportion of BrdU+ T cells. By contrast, IL2Ralpha-/- mice possess increased total numbers of LP T cells, despite normal proportions of BrdU+ LP T cells. Finally, wild-type and IL2Ralpha-/- LP T cells are equivalently Fas sensitive. These results demonstrate that LP T cells proliferate and are Fas-sensitive cells. IL2Ralpha-/- mice accumulate a large number of these Fas-sensitive LP T cells and clearly differ from Fas-deficient lpr/lpr mice in this regard. Thus our studies reveal that Fas is dispensable for LP T cell homeostasis and suggest that the intestinal inflammation observed in IL2Ralpha-/- mice is independent of defective Fas-induced cell death.