FGB1 and WSC3 are in planta-induced beta-glucan-binding fungal lectins with different functions

In the root endophyte Serendipita indica, several lectin-like members of the expanded multigene family of WSC proteins are transcriptionally induced in planta and are potentially involved in beta-glucan remodeling at the fungal cell wall. Using biochemical and cytological approaches we show that one of these lectins, SiWSC3 with three WSC domains, is an integral fungal cell wall component that binds to long-chain beta 1-3-glucan but has no affinity for shorter beta 1-3- or beta 1-6-linked glucose oligomers. Comparative analysis with the previously identified beta-glucan-binding lectin SiFGB1 demonstrated that whereas SiWSC3 does not require beta 1-6-linked glucose for efficient binding to branched beta 1-3-glucan, SiFGB1 does. In contrast to SiFGB1, the multivalent SiWSC3 lectin can efficiently agglutinate fungal cells and is additionally induced during fungus-fungus confrontation, suggesting different functions for these two beta-glucan-binding lectins. Our results highlight the importance of the beta-glucan cell wall component in plant-fungus interactions and the potential of beta-glucan-binding lectins as specific detection tools for fungi in vivo

Automatic Tumor-Stroma Separation in Fluorescence TMAs Enables the Quantitative High-Throughput Analysis of Multiple Cancer Biomarkers

The upcoming quantification and automation in biomarker based histological tumor evaluation will require computational methods capable of automatically identifying tumor areas and differentiating them from the stroma. As no single generally applicable tumor biomarker is available, pathology routinely uses morphological criteria as a spatial reference system. We here present and evaluate a method capable of performing the classification in immunofluorescence histological slides solely using a DAPI background stain. Due to the restriction to a single color channel this is inherently challenging. We formed cell graphs based on the topological distribution of the tissue cell nuclei and extracted the corresponding graph features. By using topological, morphological and intensity based features we could systematically quantify and compare the discrimination capability individual features contribute to the overall algorithm. We here show that when classifying fluorescence tissue slides in the DAPI channel, morphological and intensity based features clearly outpace topological ones which have been used exclusively in related previous approaches. We assembled the 15 best features to train a support vector machine based on Keratin stained tumor areas. On a test set of TMAs with 210 cores of triple negative breast cancers our classifier was able to distinguish between tumor and stroma tissue with a total overall accuracy of 88%. Our method yields first results on the discrimination capability of features groups which is essential for an automated tumor diagnostics. Also, it provides an objective spatial reference system for the multiplex analysis of biomarkers in fluorescence immunohistochemistry

Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmö Preventive Project)

Aims Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied. Methods and results Prospective data of the Swedish 'Malmö Preventive Project' (n = 33 346, 67.3% men, mean age 45.7 +/- 7.4 years, mean follow-up 22.7 +/- 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall >/=30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3-1.9, P /=15 mmHg (HR: 1.4, 95% CI 1.1-1.9, P = 0.024 and 1.7, 95% CI 1.1-2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction. Conclusion Orthostatic hypotension can be detected in approximately 6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease

Irish pig farmer's perceptions and experiences of tail and ear biting.

peer-reviewedAbnormal behaviours such as ear and tail biting of pigs is of significant welfare and economic concern. Currently, pig welfare legislation is under renewed focus by the EU commission and is likely to be enforced more thoroughly. The legislation prohibits routine tail docking and requires adequate enrichment to be provided. In Ireland, tail-docking is still the most utilised control mechanism to combat tail biting, but biting is still widespread even in tail-docked pigs. In addition, as pig farms are almost all fully slatted, bedding type material cannot be provided. Thus, the opinions, and practices of farmers in countries like Ireland, which may need to make significant adaptations to typical pig management systems soon, need to be considered and addressed. We carried out a survey of pig farmers during 2015 in order to gain a greater understanding of the extent of biting on Irish farms, perception on the most important preventive measures, current enrichment use and actions following outbreaks. Fifty-eight farmers from 21 Counties responded with an average herd size of 710 ± 597 sows (range 90–3000 sows). Only two farms had experienced no biting in the last year. Of the farms that had experienced tail biting (88%), 86% had also experienced ear biting. The most common concerns relating to biting were condemnation and reduced productivity of bitten pigs with both receiving an average score of 4 (most serious). Ear biting occurred most commonly in the 2nd stage (approximately 47–81 days from weaning) weaner and tail biting in the finishing stage. The most important preventive measures were felt to be taking care of animal health, restricting density, maintaining an even quality of feed/content and maintaining good air movement. Sixty-five percent of respondents added additional enrichment following an outbreak. Chains were the most common form of enrichment currently used (83%). Those not using chains favoured wood, toys and rope (17%). Identification of the most effective and accessible control and prevention measures both for the animals and for the farming community is thus essential. Improved understanding of the concerns and practices of producers, which this survey contributes to, is a first step towards this aim

Reduced microvascular density in omental biopsies of children with chronic kidney disease

Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD.Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease

Tracing digital transformation in educational organizations

This chapter describes the quantitative approaches for assessing various aspects of digital transformation from the joint research and development project #ko.vernetzt. In an application-oriented case study approach, the operationalization of a maturity model of digital transformation for educational organizations (MMEO) and the design and implementation of a multi-perspective evaluation concept are outlined. While the MMEO provides a state perspective on the digital transformation of an educational organization and its employees, the evaluation concept aims at tracing developments of media-related professional competencies. MMEO has been implemented in a study with N = 222 participants, while N = 59 learners were subject to the evaluation polls. The results provide the necessary evidence for implementing and continuously improving a qualification program in the regarded research context. However, the methodology can also be transferred to other organizations in the education sector and beyond