Bovine colostrum whey: Postpartum changes of particle size distribution and immunoglobulin G concentration at different filtration pore sizes

Bovine colostrum, as vital as it is for calves, is also a valuable source of functional components with rich health benefits for humans. Bovine colostrum whey consists of a large number of bioactive proteins and peptides. The most abundant of these is IgG. Particle size distribution (PSD) is an important feature of many of the processes in the dairy food industries. Despite this, scientific literature on PSD of colostrum whey is scarce. The goal of this research was to describe bovine colostrum whey PSD with an emphasis on postpartum milking time, filtration (pore size 450, 100, and 20 nm), IgG concentration, and lactation number. For this purpose, 4 postpartum milking colostrum samples were sequentially milked from 46 Holstein cows at 12 ± 1 h intervals. Colostrum whey was prepared by renneting and diluted (1:200) for PSD analyses by a Malvern Zetasizer Nano ZS (Malvern Instruments Ltd., Malvern, UK). Immunoglobulin G concentration of these diluted colostrum whey samples were analyzed by an Octet K2 (Molecular Devices LLC, San Jose, CA) system. Linear mixed model analysis revealed significant effects of filter pore size, postpartum milking, and lactation on colostrum whey IgG concentrations. The percentage of particles in the size interval 5 to 15 nm (the hydrodynamic diameter of IgG is around 10 nm) had an intermediate positive correlation (r = 0.50) with IgG concentration. Furthermore, we showed that PSD was associated with IgG concentration, postpartum milking time, and lactation number. The PSD measurement results showed the mean hydrodynamic diameter of 100 nm pore size filtered colostrum whey to be around 10 nm. This, with the IgG concentration results, suggests that even though the size of IgG is around 10 nm, a 100 nm pore size is adequate for membrane-involved IgG separations. In terms of energy efficiency of the filtration process, the use of a larger filter pore size can make a remarkable difference, for example, in pressurizing and cooling costs. Our work contributes to the development of sustainable and widely available colostrum-derived food and feed supplements.This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 810630 “ERA Chair for Food (By-) Products Valorisation Technologies of the Estonian University of Life Sciences (VALORTECH)” and the Estonian University of Life Sciences research and development base financing (P170195VLTQ). The authors declare no conflict of interest

Saving lives in road traffic—ethical aspects

Aim: This article aims at giving an overview of five ethical problem areas relating to traffic safety, thereby providing a general framework for analysing traffic safety from an ethical perspective and encouraging further discussion concerning problems, policies and technology in this area. Subjects and methods: The problems presented in the article are criminalisation, paternalism, privacy, justice and responsibility, and the reasons for choosing these are the following. First, they are all important areas in moral philosophy. Second, they are fairly general and it should be possible to categorise more specific problems under these headings. Ethical aspects of road traffic have not received the philosophical attention they deserve. Every year, more than 1 million people die globally in traffic accidents, and 20 to 50 million people are injured. Ninety per cent of the road traffic fatalities occur in low- and middle-income countries, where it is a growing problem. Politics, economics, culture and technology affect the number of fatalities and injuries, and the measures used to combat deaths in traffic as well as the role of road traffic should be ethically scrutinised. The topics are analysed and discussed from a moral-philosophical perspective, and the discussion includes both theory and applications. Results and conclusion: The author concludes with some thoughts on how the ethical discussion can be included in the public debate on how to save lives in road traffic. People in industrialised societies are so used to road traffic that it is almost seen as part of nature. Consequently, we do not acknowledge that we can introduce change and that we can affect the role we have given road traffic and cars. By acknowledging the ethical aspects of road traffic and illuminating the way the choices society makes are ethically charged, it becomes clear that there are alternative ways to design the road traffic system. The most important general conclusion is that discussion concerning these alternative ways of designing the system should be encouraged

Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression

Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets.Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography.Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGF\u3b2, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGF\u3b2-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGF\u3b2 are increased in osteosarcoma patients.Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGF\u3b2-blocking agents as new therapeutic options for osteosarcoma patients. Clin Cancer Res; 23(14); 3721-33. \ua92017 AACR

Diaphragm Muscle Weakness in an Experimental Porcine Intensive Care Unit Model

In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit

The Compact Linear Collider (CLIC) - 2018 Summary Report

The Compact Linear Collider (CLIC) is a TeV-scale high-luminosity linear $e^+e^-$ collider under development at CERN. Following the CLIC conceptual design published in 2012, this report provides an overview of the CLIC project, its current status, and future developments. It presents the CLIC physics potential and reports on design, technology, and implementation aspects of the accelerator and the detector. CLIC is foreseen to be built and operated in stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. CLIC uses a two-beam acceleration scheme, in which 12 GHz accelerating structures are powered via a high-current drive beam. For the first stage, an alternative with X-band klystron powering is also considered. CLIC accelerator optimisation, technical developments and system tests have resulted in an increased energy efficiency (power around 170 MW) for the 380 GeV stage, together with a reduced cost estimate at the level of 6 billion CHF. The detector concept has been refined using improved software tools. Significant progress has been made on detector technology developments for the tracking and calorimetry systems. A wide range of CLIC physics studies has been conducted, both through full detector simulations and parametric studies, together providing a broad overview of the CLIC physics potential. Each of the three energy stages adds cornerstones of the full CLIC physics programme, such as Higgs width and couplings, top-quark properties, Higgs self-coupling, direct searches, and many precision electroweak measurements. The interpretation of the combined results gives crucial and accurate insight into new physics, largely complementary to LHC and HL-LHC. The construction of the first CLIC energy stage could start by 2026. First beams would be available by 2035, marking the beginning of a broad CLIC physics programme spanning 25-30 years