Synthesis of tumor-associated MUC1-glycopeptides and their multivalent presentation by functionalized gold colloids

The mucin MUC1 is a glycoprotein involved in fundamental biological processes, which can be found over-expressed and with a distinctly altered glycan pattern on epithelial tumor cells; thus it is a promising target structure in the quest for effective carbohydrate-based cancer vaccines and immunotherapeutics. Natural glycopeptide antigens indicate only a low immunogenicity and a T-cell independent immune response; however, this major drawback can be overcome by coupling of glycopeptide antigens multivalently to immunostimulating carrier platforms. In particular, gold nanoparticles are well suited as templates for the multivalent presentation of glycopeptide antigens, due to their remarkably high surface-to-volume ratio in combination with their high biostability. In this work the synthesis of novel MUC1-glycopeptide antigens and their coupling to gold nanoparticles of different sizes are presented. In addition, the development of a new dot-blot immunoassay to test the potential antigen-antibody binding is introduced

Risk for pelvic metastasis and role of pelvic lymphadenectomy in node-positive vulvar cancer - results from the AGO-VOP.2 QS vulva study

Simple Summary In node-positive vulvar squamous cell cancer, questions of when and how to perform pelvic lymphadenectomy (LAE) as well as the optimal extent of pelvic treatment in general have been surrounded by considerable controversy. In Germany, systematic pelvic LAE is currently recommended as a staging procedure in patients at risk for pelvic nodal involvement in order to prevent morbidity caused by pelvic radiotherapy (RT) in patients without histologically-confirmed pelvic involvement. However, the population at risk for pelvic metastases remains insufficiently described, resulting in the potential overtreatment of a considerable proportion of patients with groin-positive disease. This applies to the indication to perform surgical staging but also to adjuvant RT of the pelvis without previous pelvic staging. Our study aims to describe the risk for pelvic lymph node metastasis with regard to positive groin nodes and to clarify the indication criteria for pelvic treatment in node-positive vulvar cancer. Abstract The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b

Towards Experimental Handbooks in Catalysis

The “Seven Pillars” of oxidation catalysis proposed by Robert K. Grasselli represent an early example of phenomenological descriptors in the field of heterogeneous catalysis. Major advances in the theoretical description of catalytic reactions have been achieved in recent years and new catalysts are predicted today by using computational methods. To tackle the immense complexity of high-performance systems in reactions where selectivity is a major issue, analysis of scientific data by artificial intelligence and data science provides new opportunities for achieving improved understanding. Modern data analytics require data of highest quality and sufficient diversity. Existing data, however, frequently do not comply with these constraints. Therefore, new concepts of data generation and management are needed. Herein we present a basic approach in defining best practice procedures of measuring consistent data sets in heterogeneous catalysis using “handbooks”. Selective oxidation of short-chain alkanes over mixed metal oxide catalysts was selected as an example.DFG, 390540038, EXC 2008: Unifying Systems in Catalysis "UniSysCat

Heat-induced gene positioning in "Caenorhabdidtis elegans" : "hsp-16" promoter drives transcription-dependent nuclear pore association

The DNA of eukaryotic cells is packaged into transcriptionally active euchromatin and repressed heterochromatin. These two chromatin types are non-randomly distributed within the nucleus. Indeed, at the nuclear periphery, heterochromatin is enriched near the nuclear lamina whereas euchromatin is found in the vicinity of nuclear pores. Interestingly, in budding yeast, several stress inducible genes interact with nuclear pores upon activation, although the relevance of this in higher eukaryotes has been unclear. In this thesis I characterise the spatial distribution of a heat shock gene (hsp16.2) in embryos of the nematode worm Caenorhabditis elegans. I find that hsp-16.2 is preferencially found at the nuclear periphery, where it interacts with the nuclear pore complex. Using two different types of ectopically integrated hsp-16.2 promoters, I investigated the molecular mechanism of the pore-gene interaction. I find that both types of transgenes show the same distribution, even though to a lesser extent. The results presented here shed light on the promoter elements and proteins essential for the perinuclear gene localisation and suggest conservation of gene-pore interactions in yeast, worm and fly

The survival and demise of the state: a dynamic theory of secessions

Trabajo presentado en la NES CSDSI International Conference:“Towards Effective and Equitable Development: the Role of Institutions and Diversity”, celebrada en Moscú los días 15 y 16 de diciembre de 2017N

Synthesis of tumor-associated MUC1-glycopeptides and their multivalent presentation by functionalized gold colloids

The mucin MUC1 is a glycoprotein involved in fundamental biological processes, which can be found over-expressed and with a distinctly altered glycan pattern on epithelial tumor cells; thus it is a promising target structure in the quest for effective carbohydrate-based cancer vaccines and immunotherapeutics. Natural glycopeptide antigens indicate only a low immunogenicity and a T-cell independent immune response; however, this major drawback can be overcome by coupling of glycopeptide antigens multivalently to immunostimulating carrier platforms. In particular, gold nanoparticles are well suited as templates for the multivalent presentation of glycopeptide antigens, due to their remarkably high surface-to-volume ratio in combination with their high biostability. In this work the synthesis of novel MUC1-glycopeptide antigens and their coupling to gold nanoparticles of different sizes are presented. In addition, the development of a new dot-blot immunoassay to test the potential antigen-antibody binding is introduced

Adipokines at the crossroad between obesity and cardiovascular disease

Obesity, and especially excessive visceral adipose tissue accumulation, is considered as a low-grade inflammatory state that is responsible for adipocyte dysfunction and associated metabolic disorders. Adipose tissue displays endocrine functions by releasing pro- or anti-inflammatory bioactive molecules named adipokines. An altered expression of these molecules, provoked by obesity or adipocyte dysregulation, contributes to major metabolic diseases such as insulin resistance and type 2 diabetes mellitus that are important risk factors for cardiovascular disease. However, obesity is also characterised by the expansion of perivascular adipose tissue that acts locally via diffusion of adipokines into the vascular wall. Local inflammation within blood vessels induced by adipokines contributes to the onset of endothelial dysfunction, atherosclerosis and thrombosis, but also to vascular remodelling and hypertension. A fast expansion of obesity is expected in the near future, which will rapidly increase the incidence of these cardiovascular diseases. The focus of this review is to summarise the link between metabolic and cardiovascular disease and discuss current treatment approaches, limitations and future perspectives for more targeted therapies

New evidence for old lore - Urinary bladder distension on post-mortem computed tomography is related to intoxication

INTRODUCTION: Distension of the urinary bladder is reported to be a sign of intoxication at autopsy. The purpose of this study was to compare radiologically calculated urinary bladder volume (UBV) to autopsy measurements of UBV, and to investigate the relationship between intoxication and calculated UBV. MATERIALS AND METHODS: Autopsy reports, toxicology reports and post-mortem CTs of 332 adult human cadavers were retrospectively analyzed, 259 cases were included in the final population. Spearman's rho test was used to compare calculated UBV to autopsy measurements. Significance levels for UBV in relation to toxicology results were investigated with the Mann-Whitney test. Spearman's rho test was also used to correlate the widest left-right bladder diameter on axial images to calculated UBV. Both calculated UBV and axial diameters were subjected to receiver operating characteristics curve analysis. Sensitivity and specificity were calculated for individual cutoff values. RESULTS: There is a strong correlation and high consistency (r=0.92, p330ml indicate positive toxicology results with a sensitivity/specificity of 40%/87% and 25%/97% respectively. Axial urinary bladder diameter of 8.5cm and >10cm indicate positive toxicology results with a sensitivity/specificity of 36%/85% and 16%/95% respectively. CONCLUSIONS: Radiologically calculated UBV accurately represents the autoptically measured UBV. The occurrence of urinary bladder distension on post-mortem imaging should raise suspicion of intoxication