Schaumbildungseigenschaften von Milchproteinfraktionen und -hydrolysaten

Ziel der Dissertation war die Gewinnung von angereicherten Milchproteinfraktionen mit Lebensmittelqualität im Technikummaßstab, die enzymatische Modifizierung von Milchproteinen und Milchproteinfraktionen sowie die Prüfung der resultierenden Schaumbildungseigenschaften. Magermilchproteine wurden mit Hilfe von Membranverfahren in eine micellare Caseinfraktion und eine Molkenproteinfraktion getrennt. Verfahren zur Gewinnung von angereicherten Casein- und Molkenproteinfraktionen im Technikummaßstab konnten im Rahmen der Untersuchungen in Bezug auf den Verfahrensablauf vereinfacht und bezüglich der Ausbeute/Reinheit der Produkte optimiert werden. Milchproteine wurden enzymatisch hydrolysiert, die Hydrolysate mittels Ultrafiltration fraktioniert und getrocknet. Die Schaumbildungseigenschaften der Fraktionen und Hydrolysate wurden mittels einer Aerationsmethode verschäumt und charakterisiert. Aus den Untersuchungen zur Charakterisierung der Schaumbildungseigenschaften von Milchproteinfraktionen und –hydrolysaten wird deutlich, dass insbesondere Kombinationen aus Proteinpolymeren und –monomeren oder aus Proteinmonomeren beziehungsweise Peptidaggregaten und Peptiden in Bezug auf die Schaumbildungseigenschaften symbiotisch wirken und technologisch damit das größte Potential beinhalten

Impacts of slurry acidification and injection on fertilizer nitrogen fates in grassland

Low nitrogen (N) use efficiency of broadcast slurry application leads to nutrient losses, air and water pollution, greenhouse gas emissions and—in particular in a warming climate—to soil N mining. Here we test the alternative slurry acidification and injection techniques for their mitigation potential compared to broadcast spreading in montane grassland. We determined (1) the fate of $^{15}$N labelled slurry in the plant-soil-microbe system and soil-atmosphere exchange of greenhouse gases over one fertilization/harvest cycle and (2) assessed the longer-term contribution of fertilizer $^{15}$N to soil organic N formation by the end of the growing season. The isotope tracing approach was combined with a space for time climate change experiment. Simulated climate change increased productivity, ecosystem respiration, and net methane uptake irrespective of management, but the generally low N$_2$O fluxes remained unchanged. Compared to the broadcast spreading, slurry acidification showed lowest N losses, thus increased productivity and fertilizer N use efficiency (38% $^{15}$N recovery in plant aboveground plant biomass). In contrast, slurry injection showed highest total fertilizer N losses, but increased fertilization-induced soil organic N formation by 9–12 kg N ha$^{−1}$ season$^{−1}$. Slurry management effects on N$_2$O and CH$_4$ fluxes remained negligible. In sum, our study shows that the tested alternative slurry application techniques can increase N use efficiency and/or promote soil organic N formation from applied fertilizer to a remarkable extent. However, this is still not sufficient to prevent soil N mining mostly resulting from large plant N exports that even exceed total fertilizer N inputs

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

A pan-European study of the C9orf72 repeat associated with FTLD : geographic prevalence, genomic instability, and intermediate repeats

We assessed the geographical distribution of C9orf72 G4C2 expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n=1,205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.98% in overall FTLD, with 18.52% in familial, and 6.26% in sporadic FTLD patients. Outliers were Finland and Sweden with overall frequencies of respectively 29.33% and 20.73%, but also Spain with 25.49%. In contrast, prevalence in Germany was limited to 4.82%. In addition, we studied the role of intermediate repeats (724 repeat units), which are strongly correlated with the risk haplotype, on disease and C9orf72 expression. In vitro reporter gene expression studies demonstrated significantly decreased transcriptional activity of C9orf72 with increasing number of normal repeat units, indicating that intermediate repeats might act as predisposing alleles and in favor of the loss-of-function disease mechanism. Further, we observed a significantly increased frequency of short indels in the GC-rich low complexity sequence adjacent to the G4C2 repeat in C9orf72 expansion carriers (P<0.001) with the most common indel creating one long contiguous imperfect G4C2 repeat, which is likely more prone to replication slippage and pathological expansion

A Pan‐ E

peer reviewedWe assessed the geographical distribution of C9orf72 G(4) C(2) expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n = 1,205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.98% in overall FTLD, with 18.52% in familial, and 6.26% in sporadic FTLD patients. Outliers were Finland and Sweden with overall frequencies of respectively 29.33% and 20.73%, but also Spain with 25.49%. In contrast, prevalence in Germany was limited to 4.82%. In addition, we studied the role of intermediate repeats (7-24 repeat units), which are strongly correlated with the risk haplotype, on disease and C9orf72 expression. In vitro reporter gene expression studies demonstrated significantly decreased transcriptional activity of C9orf72 with increasing number of normal repeat units, indicating that intermediate repeats might act as predisposing alleles and in favor of the loss-of-function disease mechanism. Further, we observed a significantly increased frequency of short indels in the GC-rich low complexity sequence adjacent to the G(4) C(2) repeat in C9orf72 expansion carriers (P < 0.001) with the most common indel creating one long contiguous imperfect G(4) C(2) repeat, which is likely more prone to replication slippage and pathological expansion

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency <0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency <0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology.status: publishe