Lysine blockage of milk proteins in infant formula impairs overall protein digestibility and peptide release

During heat processing of milk and dairy products, for example infant formula, the Maillard reaction occurs. In vitro and animal studies suggest that Maillard reaction induced lysine blockage impairs protein digestibility. Most studies that investigate the effect of glycation on protein digestion use a mixture of isolated milk protein with reducing sugars. In this study, infant formulas with 6.5%, 8.4%, 11.2%, 14.8%, 20.8%, and 44.5% of blocked lysine (BL) were digested in an in vitro infant digestion model and tested for protein hydrolysis and peptide release. OPA (o-phthalaldehyde) assay was used to assess the degree of protein hydrolysis. SDS-PAGE was conducted to monitor the hydrolysis of specific proteins. Peptides formed after gastric and intestinal digestion were identified by LC/MS. Protein hydrolysis of the 6.5% BL sample was significantly higher after 10 minutes of intestinal digestion compared to all other samples. Most differences were observed after intestinal digestion. A significant change in peptide patterns was observed for the 45% BL sample resulting in a relatively higher number of peptides with more than 14 amino acids. Mainly casein-derived peptides were affected. Overall, the average peptide length was significantly increased for the 44.5% BL glycated product (on average 10.2 amino acids for 6-21% BL vs. 11.4 amino acids for 45% BL; p < 0.001). In conclusion, glycation of milk proteins in an infant formula product can impair overall protein digestibility. These findings emphasize the importance of mild processing and having low BL levels in infant formula to ensure optimal digestion of proteins.</p

A probabilistic analysis of argument cogency

This paper offers a probabilistic treatment of the conditions for argument cogency as endorsed in informal logic: acceptability, relevance, and sufficiency. Treating a natural language argument as a reason-claim-complex, our analysis identifies content features of defeasible argument on which the RSA conditions depend, namely: change in the commitment to the reason, the reason’s sensitivity and selectivity to the claim, one’s prior commitment to the claim, and the contextually determined thresholds of acceptability for reasons and for claims. Results contrast with, and may indeed serve to correct, the informal understanding and applications of the RSA criteria concerning their conceptual dependence, their function as update-thresholds, and their status as obligatory rather than permissive norms, but also show how these formal and informal normative approachs can in fact align

Linear response within the projection-based renormalization method: Many-body corrections beyond the random phase approximation

The explicit evaluation of linear response coefficients for interacting many-particle systems still poses a considerable challenge to theoreticians. In this work we use a novel many-particle renormalization technique, the so-called projector-based renormalization method, to show how such coefficients can systematically be evaluated. To demonstrate the prospects and power of our approach we consider the dynamical wave-vector dependent spin susceptibility of the two-dimensional Hubbard model and also determine the subsequent magnetic phase diagram close to half-filling. We show that the superior treatment of (Coulomb) correlation and fluctuation effects within the projector-based renormalization method significantly improves the standard random phase approximation results.Comment: 17 pages, 7 figures, revised versio

Violacein Induces Death of Resistant Leukaemia Cells via Kinome Reprogramming, Endoplasmic Reticulum Stress and Golgi Apparatus Collapse

It is now generally recognised that different modes of programmed cell death (PCD) are intimately linked to the cancerous process. However, the mechanism of PCD involved in cancer chemoprevention is much less clear and may be different between types of chemopreventive agents and tumour cell types involved. Therefore, from a pharmacological view, it is crucial during the earlier steps of drug development to define the cellular specificity of the candidate as well as its capacity to bypass dysfunctional tumoral signalling pathways providing insensitivity to death stimuli. Studying the cytotoxic effects of violacein, an antibiotic dihydro-indolone synthesised by an Amazon river Chromobacterium, we observed that death induced in CD34(+)/c-Kit(+)/P-glycoprotein(+)/MRP1(+) TF1 leukaemia progenitor cells is not mediated by apoptosis and/or autophagy, since biomarkers of both types of cell death were not significantly affected by this compound. To clarify the working mechanism of violacein, we performed kinome profiling using peptide arrays to yield comprehensive descriptions of cellular kinase activities. Pro-death activity of violacein is actually carried out by inhibition of calpain and DAPK1 and activation of PKA, AKT and PDK, followed by structural changes caused by endoplasmic reticulum stress and Golgi apparatus collapse, leading to cellular demise. Our results demonstrate that violacein induces kinome reprogramming, overcoming death signaling dysfunctions of intrinsically resistant human leukaemia cells.TopInstitute pharma (The Netherlands)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Dutch Cancer SocietyErasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, NetherlandsUniv Estadual Campinas, Brazil UNICAMP, Dept Biochem, Inst Biol, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Biochem, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Cell Biol, São Paulo, BrazilUniv Grande Rio UNIGRANRIO, Heath Sci Sch, Multidisciplinary Lab Dent Res, Rio de Janeiro, BrazilNatl Inst Metrol Qual & Technol Inmetro, Biotechnol Lab, Bioengn Sect, Rio de Janeiro, BrazilUniv Campinas UNICAMP, Inst Chem, Biol Chem Lab, Rio de Janeiro, BrazilUniv Groningen, Univ Med Ctr Groningen, Dept Pediat Oncol, Beatrix Childrens Hosp, Groningen, NetherlandsFed Univ São Paulo UNIFESP, Dept Biochem, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Cell Biol, São Paulo, BrazilDutch Cancer Society: EMCR 2010-4737Web of Scienc

DC and AC Tests of Moisture Electrical Pressboard Impregnated with Mineral Oil or Synthetic Ester—Determination of Water Status in Power Transformer Insulation

In this study, the conductivity and permittivity of electrical pressboard—insulating liquid—water composites were investigated, and the electrical properties of the composites and water were analysed comparatively. Mineral oil and synthetic ester were used as insulating liquids. It was found that the presence of water caused an increase in the permeability of the composite in the frequency range below 100 Hz. The value of static permittivity determined by water in the content of 5 wt. % was approximately 15. To obtain this value caused by liquid water, its volume should be approximately five (oil) and four times (ester) higher than its actual content, respectively. The determined values of the activation energy of the DC conductivity of the composites were several times higher than the values of the activation energy of the conductivity of the liquid water. The experimental values of the dielectric relaxation times were many orders of magnitude higher than the dielectric relaxation times of water. This means that the experimental results obtained for the dielectric permittivity, the activation energy of conductivity and the dielectric relaxation times for moisture electrical pressboard impregnated by mineral oil or synthetic ester exclude the possibility of the presence of liquid water in the composites. It was found that the conductivity of the composites increased exponentially with increasing water content. Such dependencies are characteristic of hopping conductivity, caused by the quantum phenomenon of electron tunnelling between nanometre-sized potential wells. As the increase in conductivity is determined by the presence of water in the composites, therefore, the nanometre potential wells were single-water molecules or nanodrops

Serumproteinbindung von ACTH

3H- 1–23-Corticotropin wurde an Dextrangel (Sephadex G-25) gebunden und konnte durch Serumproteine, Albumin oder 0,1 N HCl eluiert werden. Mittels Dextrangelfiltration wurde gefunden, daß3H-ACTH kompetitiv an Serumproteine (Albumin) und Dextrangel gebunden wurde. Auch für natürliches Schweine-ACTH und endogenes ACTH in Patientenplasma (Adrenalektomie) wurde mittels biologischer ACTH-Bestimmung die Bindung von ACTH an Proteine bestätigt.3H- 1–23 corticotropin was bound to dextran gel (sephadex G-25) and was eluted by either serum proteins, albumin or 0.1 N HCl. Competitive binding of3H-ACTH to serum proteins (albumin) and dextran gel was shown by dextran gel filtration. Likewise natural ACTH (pig) and endogenous ACTH from plasma of an adrenalectomized patient were shown to be partly protein bound using biological ACTH-assay

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway