Engineering of camel chymosin for improved cheese properties

More than 20 Mio tons of cheese are produced world-wide per year. By improving cheese yield and quality through process optimization, the amount of milk needed for manufacturing can be reduced significantly. Chymosin, an aspartic acid protease, is initiating milk coagulation in cheese manufacturing by cleaving off the glycomacropeptide (GMP) from the surface of casein micelles. Non-specific proteolysis of casein molecules by chymosin during this milk clotting process releases soluble peptides into the whey, resulting in protein losses from the cheese. The ratio between specific clotting activity (C) and non-specific proteolysis (P) of a coagulant can therefore be used as predictor for cheese yield. During ripening of the cheese, remaining coagulant continues proteolytic break-down of the caseins with significant impact on cheese properties. While the main proteolytic activity, the release of N-terminal peptides from alphaS1 casein (alphaS1-N), is associated with cheese softening and loss of firmness, cleavage of the C-terminal end of beta casein (beta-C) contributes to unwanted bitterness of the cheese [1]. The chymosin from Bos taurus (bovine chymosin) is traditionally used as milk coagulant in cheese manufacture. However, the homologous enzyme from Camelus dromedarius (camel chymosin) has been shown to be a superior alternative for various cheese types, since it reveals higher specific activity (C) and specificity (C/P) for the milk clotting reaction [2], as well as lower alphaS1 and beta casein proteolysis during ripening (Fig. 1). Please click Additional Files below to see the full abstract

Multidimensional engineering of Chymosin for efficient cheese production by machine learning guided directed evolution

The global cheese market today exceeds $100B/year. Chymosin (a.k.a. rennin) is an aspartic endopeptidase produced by the stomach lining of new-born mammals. During cheese production chymosin is added to the milk where it cleaves the glycomacropeptide (GMP) from the surface of casein micelles to initiate milk coagulation. Current commercial recombinant chymosin enzymes derived from Bos taurus (cow) or Camelus dromedarius (camel) are limited in their proteolytic specificity leading to incomplete milk-to-cheese conversion. Increasing the chymosin specificity for GMP cleavage would significantly decrease the amount of milk needed for cheese production thereby reducing cost and decreasing environmental footprint of the dairy industry. Separate from milk coagulation, chymosin dependent release of N-terminal peptides from alphaS1 casein during cheese ripening leads to unwanted softening, accompanied with cheese loss during industrial processing such as slicing and shredding. Furthermore, chymosin dependent cleavage of the C-terminal end of beta casein contributes to unwanted bitterness of the cheese. Improvement of chymosin proteolytic specificity in both milk coagulation and cheese ripening is consequently of high commercial relevance. Please click Additional Files below to see the full abstract

POWER ON DIGRAPHS

It is assumed that relations between n players are represented by a directed graph or digraph. Such a digraph is called invariant if there is a link (arc) between any two players between whom there is also a directed path. We characterize a class of power indices for invariant digraphs based on four axioms: Null player, Constant sum, Anonymity, and the Transfer property. This class is determined by 2n - 2 parameters. By considering additional conditions about the effect of adding a directed link between two players, we single out three different, one-parameter families of power indices, reflecting several well-known indices from the literature: the Copeland score, beta- and apex type indices

De staat moet zich niet bemoeien met religieuze praktijken

De bescherming van fundamentele rechten in een integrerend Europ

Do inhabitants profit from integrating a public health focus in urban renewal programmes?:A Dutch case study

Background Urban renewal traditionally involves policy sectors such as housing, transport, and employment, which potentially can enhance the health of residents living in deprived areas. Additional involvement of the public health sector might increase the health impact of these urban renewal activities. This study evaluates the health impact of an additional focus on health, under the heading of Healthy District Experiments (HDE), within districts where an urban renewal programme was carried out. Methods We evaluated changes in health outcomes before the start of the HDE and after implementation, and compared these changes with health changes in control areas, e.g. districts from the urban renewal programme where no additional HDE was implemented. Additionally, we gathered information on the content of the experiments to determine what types of activities have been implemented. Results The additional activities from the HDE were mostly aimed at strengthening the health care in the districts and at promoting physical activity. When we compared the prevalence in general health, mental health, overweight, obesity, smoking, and physical activity during the study period between the HDE districts and control districts, we found no significant differences in the rate of change. The study is limited by a small sample size and the cross-sectional nature of the data. These and other limitations are discussed. Conclusion We found no evidence for a beneficial health impact of the activities that were initiated with a specific focus on health, within a Dutch urban renewal programme. Specific attention for network management and the integration of such activities in the wider programme, as well as an allocated budget might be needed in order to sort a health impact

Determinants and consequences of polypharmacy in patients with a depressive disorder in later life

OBJECTIVES: Polypharmacy and late-life depression often congregate in the geriatric population. The primary objective is to identify determinants of polypharmacy in patients with depression, and second to examine polypharmacy in relation to various clinical phenotypes of depression and its course. METHODS: A longitudinal observational study using data of the Netherlands Study of Depression in Older persons (NESDO) including 375 patients with depression ≥ 60 years and 132 non-depressed comparisons. Linear and logistic regression were used to analyze both polypharmacy (dichotomous: ≥ 5 medications) and number of prescribed drugs (continuous) in relation to depression, various clinical phenotypes, and depression course. RESULTS: Polypharmacy was more prevalent among patients with depression (46.9%) versus non-depressed comparisons (19.7%). A lower level of education, lower cognitive functioning, and more chronic diseases were independently associated with polypharmacy. Adjusted for these determinants, polypharmacy was associated with a higher level of motivational problems, anxiety, pain, and an earlier age of onset. A higher number of drugs was associated with a worse course of late-life depression (OR=1.24 [95% CI: 1.03 - 1.49], p=.022). CONCLUSION: Older patients with depression have a huge risk of polypharmacy, in particular among those with an early onset depression. As an independent risk factor for chronic depression, polypharmacy needs to be identified and managed appropriately. Findings suggest that depression moderates polypharmacy through shared risk factors, including motivational problems, anxiety, and pain. The complex interaction with somatic health burden requires physicians to prescribe medications with care

Modelling the rotation period distribution of M dwarfs in the Kepler field

McQuillan et al. (Mon. Not. R. Astron. Soc.432:1203, 2013) presented 1570 periods P of M dwarf stars in the field of view of the Kepler telescope. It is expected that most of these reflect rotation periods, due to starspots. It is shown here that the data can be modelled as a mixture of four subpopulations, three of which are overlapping log-normal distributions. The fourth subpopulation has a power law distribution, with P −1/2. It is also demonstrated that the bulk of the longer periods, representing the two major sub-populations, could be drawn from a single subpopulation, but with a period-dependent probability of observing half the true period

Topologically stable magnetization states on a spherical shell: curvature-stabilized skyrmions

Topologically stable structures include vortices in a wide variety of matter, skyrmions in ferro- and antiferromagnets, and hedgehog point defects in liquid crystals and ferromagnets. These are characterized by integer-valued topological quantum numbers. In this context, closed surfaces are a prominent subject of study as they form a link between fundamental mathematical theorems and real physical systems. Here we perform an analysis on the topology and stability of equilibrium magnetization states for a thin spherical shell with easy-axis anisotropy in normal directions. Skyrmion solutions are found for a range of parameters. These magnetic skyrmions on a spherical shell have two distinct differences compared to their planar counterpart: (i) they are topologically trivial and (ii) can be stabilized by curvature effects, even when Dzyaloshinskii-Moriya interactions are absent. Due to its specific topological nature a skyrmion on a spherical shell can be simply induced by a uniform external magnetic field