The macrostructure of milk lipids: the fat globules

The aim of this review article is to summarize the information available related to milk fat globules (MFGs) in order to highlight their contribution to the nutritional and technological characteristics of milk and dairy products. The macrostructure of milk lipids is composed of globules made up of triglycerides with different melting points, enveloped by a biological membrane from the mammary epithelial cell. In milks of different animal species, there are different sized MFGs, ranging from diameters of less than 0.2 μm to a maximum of 15 μm. The average diameter and the number of globules are affected by endogenous, physiological and exogenous factors. The size of the globules in turn affects the qualitative characteristics of milk and cheese. In addition, the average diameter of the globules and their surface that is exposed to the digestive system affect fat digestibility in different ways. Finally, the components of the milk fat globule membranes have been shown to take part in the secretion process of globules and to have a beneficial effect on human health. In conclusion, by acting on factors influencing the dimensions of the fat globules and by increasing the content of the milk membrane could help adapt milk production to specific consumer targets and improve milk nutritional properties

Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours

Endoglin/CD105 is well acknowledged as being the most reliable marker of proliferation of endothelial cells, and it is overexpressed on tumour neovasculature. Our current knowledge of its structure, physiological role, and tissue distribution suggests that targeting of endoglin/CD105 is a novel and powerful diagnostic and therapeutic strategy in human malignancies, through the imaging of tumour-associated angiogenesis and the inhibition of endothelial cell functions related to tumour angiogenesis. Among biotherapeutic agents, monoclonal antibodies have shown a major impact on the clinical course of human malignancies of different histotypes. Along this line, the potential efficacy of anti-endoglin/CD105 antibodies and their derivatives for clinical purposes in cancer is supported by a large body of available pre-clinical in vitro and in vivo data. In this review, the main findings supporting the translation of antibody-based endoglin/CD105 targeting from pre-clinical studies to clinical applications in human cancer are summarized and discussed

Current knowledge on functionality and potential therapeutic uses of donkey milk

The increase of knowledge on the composition of donkey milk has revealed marked similarities to human milk, which led to a growing number of investigations focused on testing the potential effects of donkey milk in vitro and in vivo. This paper examines the scientific evidence regarding the beneficial effects of donkey milk on human health. Most clinical studies report a tolerability of donkey milk in 82.6–98.5% of infants with cow milk protein allergies. The average protein content of donkey milk is about 18 g/L. Caseins, which are main allergenic components of milk, are less represented compared to cow milk (56% of the total protein in donkey vs. 80% in cow milk). Donkey milk is well accepted by children due to its high concentration of lactose (about 60 g/L). Immunomodulatory properties have been reported in one study in humans and in several animal models. Donkey milk also seems to modulate the intestinal microbiota, enhance antioxidant defense mechanisms and detoxifying enzymes activities, reduce hyperglycemia and normalize dyslipidemia. Donkey milk has lower calorie and fat content compared with other milks used in human nutrition (fat ranges from 0.20% to 1.7%) and a more favourable fatty acid profile, being low in saturated fatty acids (3.02 g/L) and high in alpha-linolenic acid (about 7.25 g/100 g of fat). Until now, the beneficial properties of donkey milk have been mostly related to whey proteins, among which β-lactoglobulin is the most represented (6.06 g/L), followed by α-lactalbumin (about 2 g/L) and lysozyme (1.07 g/L). So far, the health functionality of donkey milk has been tested almost exclusively on animal models. Furthermore, in vitro studies have described inhibitory action against bacteria, viruses, and fungi. From the literature review emerges the need for new randomized clinical trials on humans to provide stronger evidence of the potential beneficial health effects of donkey milk, which could lead to new applications as an adjuvant in the treatment of cardiometabolic diseases, malnutrition, and aging

Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma.

The intrinsic oncolytic specificity of vesicular stomatitis virus (VSV) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (HCC). Identifying key regulators in diverse transduction pathways that define VSV oncolysis in cancer cells represents a fundamental prerequisite to engineering more effective oncolytic viral vectors and adjusting combination therapies. After having identified defects in the signalling cascade of type I interferon induction, responsible for attenuated antiviral responses in human HCC cell lines, we have now investigated the role of cell proliferation and translation initiation. Cell cycle progression and translation initiation factors eIF4E and eIF2Bepsilon have been recently identified as key regulators of VSV permissiveness in T-lymphocytes and immortalized mouse embryonic fibroblasts, respectively. Here, we show that in HCC, decrease of cell proliferation by cell cycle inhibitors or siRNA-mediated reduction of G(1) cyclin-dependent kinase activities (CDK4) or cyclin D1 protein expression, do not significantly alter viral growth. Additionally, we demonstrate that translation initiation factors eIF4E and eIF2Bepsilon are negligible in sustaining VSV replication in HCC. Taken together, these results indicate that cellular proliferation and the initiation phase of cellular protein synthesis are not essential for successful VSV oncolysis of HCC. Moreover, our observations indicate the importance of cell-type specificity for VSV oncolysis, an important aspect to be considered in virotherapy applications in the future

Apicomplexan protozoa responsible for reproductive disorders: Occurrence of dna in blood and milk of donkeys (equus asinus) and minireview of the related literature

Donkeys may be susceptible to many pathological agents and may act as carriers of pathogens for other animal species and humans. This study evaluated the occurrence of potentially abortifacient apicomplexan protozoa DNA in blood and milk samples collected at different time periods during lactation (1, 6, and 10 months) from 33 healthy dairy jennies. A total of 73 blood and 73 milk samples were used for DNA extraction and analysis. Blood specimens from 11/33 (33%) jennies scored positive for Theileria equi, while milk samples scored negative. Blood and milk of 3/33 jennies yielded DNA of Toxoplasma gondii at 6 months (n. 1) and 10 months (n. 2) after parturition. Neospora caninum DNA was found in four milk and in five blood samples only at one month after parturition. This study is the first report about the presence of N. caninum DNA in milk of naturally infected jennies. Moreover, the excretion of N. caninum DNA in some of these jennies at 30 days from the parturition may suggest a possible occurrence of an endogenous cycle, while the presence of T. gondii DNA in the milk collected at 6 and 10 months after parturition may be suggestive of a discontinuous excretion

Tumour-derived interleukin 1alpha (IL-1alpha) up-regulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) by endothelial cells.

Levels of circulating soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in patients affected by solid malignancies; however, the cellular sources generating high levels of sICAM-1 remain to be characterized. Using conditioned media (CM) from seven ICAM-1-positive or -negative neoplastic cells, we demonstrate that tumour-derived interleukin 1alpha (IL-1alpha) significantly (P < 0.05) up-regulates the release of sICAM-1 by human umbilical vein endothelial cells. The intensity of the effect correlated with the amounts of IL-1alpha detectable in CM. Levels of ICAM-1 mRNA were also up-regulated by tumour-secreted IL-1alpha. The up-regulation of the shedding of sICAM-1 and of its expression at protein and mRNA level were completely reversed by the addition of anti-IL-1alpha neutralizing antibodies. Consistent with the in vitro data, tumour endothelia were strongly stained for ICAM-1 compared with autologous normal tissue endothelia. Taken altogether, our observations reveal an IL-1alpha-mediated tumour-endothelium relationship sustaining the shedding of sICAM-1 by endothelial cells. This is a general phenomenon in solid malignancies that correlates with the ability of neoplastic cells to secrete IL-1alpha rather than with their expression of ICAM-1 and/or histological origin. sICAM-1 has been previously shown to inhibit LFA-1/ICAM-1-mediated cell-cell interactions; therefore, the ability of neoplastic cells to secrete IL-1alpha is likely to represent a mechanism for their escape from immune interaction

Human factors in the design of sustainable built environments

Scientific research provides convincing evidence that climate change is having significant impacts on many aspects of life. In the built-environment domain, regulatory requirements are pushing the challenges of environmental, economic, and social sustainability at the core of the professional agenda, although the aims of carbon reduction and energy conservation are frequently given a priority over occupants' comfort, well-being, and satisfaction. While most practitioners declare to embrace sustainability as a driver of their professional approach, a general lack of integrated creative and technical skills hinders the design of buildings centred on articulate and comprehensive sustainability goals, encompassing, other than energy criteria, also human-centred and ethical values founded on competent and informed consideration of the requirements of the site, the programme, and the occupants. Built environments are designed by humans to host a range of human activities. In response, this article aims to endorse a sustainable approach to design founded on the knowledge arising from scholarly and evidence-based research, exploring principles and criteria for the creation and operation of human habitats that can respond to energy and legislative demands, mitigate their environmental impacts, and adapt to new climate scenarios, while elevating the quality of experience and delight to those occupying them

Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas

Ten Questions Concerning Well-Being in the Built Environment

Well-being in the built environment is a topic that features frequently in building standards and certification schemes, in scholarly articles and in the general press. However, despite this surge in attention, there are still many questions on how to effectively design, measure, and nurture well-being in the built environment. Bringing together experts from academia and the building industry, this paper aims to demonstrate that the promotion of well-being requires a departure from conventional agendas. The ten questions and answers have been arranged to offer a range of perspectives on the principles and strategies that can better sustain the consideration of well-being in the design and operation of the built environment. Placing a specific focus on some of the key physical factors (e.g., light, temperature, sound, and air quality) of indoor environmental quality (IEQ) that strongly influence occupant perception of built spaces, attention is also given to the value of multi-sensory variability, to how to monitor and communicate well-being outcomes in support of organizational and operational strategies, and to future research needs and their translation into building practice and standards. Seen as a whole, a new framework emerges, accentuating the integration of diverse new competencies required to support the design and operation of built environments that respond to the multifaceted physical, physiological, and psychological needs of their occupants