Bilayer Forming Phospholipids as Targets for Cancer Therapy

Phospholipids represent a crucial component for the structure of cell membranes. Phosphatidylcholine and phosphatidylethanolamine are two phospholipids that comprise the majority of cell membranes. De novo biosynthesis of phosphatidylcholine and phosphatidylethanolamine occurs via the Kennedy pathway, and perturbations in the regulation of this pathway are linked to a variety of human diseases, including cancer. Altered phosphatidylcholine and phosphatidylethanolamine membrane content, phospholipid metabolite levels, and fatty acid profiles are frequently identified as hallmarks of cancer development and progression. This review summarizes the research on how phospholipid metabolism changes over oncogenic transformation, and how phospholipid profiling can differentiate between human cancer and healthy tissues, with a focus on colorectal cancer, breast cancer, and non-small cell lung cancer. The potential for phospholipids to serve as biomarkers for diagnostics, or as anticancer therapy targets, is also discussed.     

Inorganic polymers made of fayalite slag: On the microstructure and behavior of Fe

The microstructure of inorganic polymers (IP) formed from fayalite slag was investigated as a function of the composition of different activating solutions. The starting slag was 80 wt% amorphous, and after activation using sodium silicate solutions with varying SiO₂/Na₂O molar ratios, the amorphous phase dissolved and a binder phase was formed. The morphology of this binder, including the population and size of remnant particles and pores, was dependent on the particular activating solution used, and became denser as the level of silicate rose. ⁵⁷Fe Mössbauer spectroscopy revealed that the IP synthesis reaction is combined with the oxidation of Fe²⁺ from the fayalite slag to Fe³⁺ in the inorganic polymer binder. The reaction extent varied and could be quantified using the absorption areas of these ions. Data corroborate that the Fe²⁺ ions in the amorphous part of the fayalite slag and the Fe³⁺ ions in the new binder phase had an average oxygen‐coordination number of 5.     

Effect of different fermentation parameters on bioethanol production from corn meal hydrolyzates by free and immobilized cells of Saccharomyces cerevisiae var. ellipsoideus

BACKGROUND: Bioethanol produced from renewable biomass, such as corn meal, is a biofuel that is both renewable and environmentally friendly. Significant scientific and technological investments will be needed to achieve substitution of conventional fossil fuels with alternative fuels. The ethanol fermentation of enzymatically obtained corn meal hydrolyzates by free and immobilized cells of Saccharomyces cerevisiae var. ellipsoideus yeast in a batch system was studied. The initial glucose and inoculum concentration and the time required for the efficient ethanol production were optimized taking into account parameters such as ethanol concentration, ethanol yield, percentage of the theoretical yield of ethanol and volumetric productivity in both immobilized and free cell systems. RESULTS: The yeast cells were immobilized in Ca–alginate by an electrostatic droplet generation method. An optimal initial inoculum concentration of 2% (v/v) and optimal fermentation time of 38 h for both immobilized and free yeasts were determined. An optimal initial glucose concentration of 150 g L^?1 for free system was achieved. At the initial glucose concentration of 176 g L no substrate or product inhibition were achieved with immobilized yeast. CONCLUSION: By immobilization of the yeast into Ca–alginate using the method of electrostatic droplet generation a superior system was realized, which exhibited lower substrate inhibition and higher tolerance to ethanol. The cells of S. cerevisiae var. ellipsoideus yeast entrapped in Ca–alginate showed good physical and chemical stability, and no substrate and product diffusion restrictions were noticed. Copyright © 2008 Society of Chemical Industry     

The impact of choline availability on muscle lipid metabolism

Consumption of choline-rich foods is essential to ensure membrane integrity, neurotransmission and genomic methylation pathways. Insufficient dietary choline supply can cause choline deficiency (CD) which manifests in the development of non-alcoholic fatty liver disease. There is very limited information regarding the effect of CD on non-hepatic tissues such as muscle. In this study, we induced CD in muscle cells and investigated the effect on choline transport, phosphatidylcholine (PC), fatty acid and triacylglycerol (TAG, fat) metabolism. Choline transport was stable across the plasma membrane of CD cells but significantly impaired in mitochondria. The main choline-transporter SLC44A1 was down-regulated by CD at the mRNA level, and SLC44A1 protein was reduced in total cell lysates and isolated mitochondria. CD significantly reduced PC synthesis but PC degradation was unaffected. PC from CD muscle was modified and contained more monounsaturated fatty acids at the expense of saturated fatty acids. Surprisingly, CD muscle cells also accumulated TAG in the form of large lipid droplets. Those droplets were formed from endogenous fatty acids and by slower TAG metabolism. This study established for the first time that choline availability affects muscle membrane lipid composition and intracellular lipid metabolism, and underlines the significance of choline-rich foods for proper muscle function.     

Optimization of fully aligned bioactive electrospun fibers for “in vitro” nerve guidance

Complex architecture of natural tissues such as nerves requires the use of multifunctional scaffolds with peculiar topological and biochemical signals able to address cell behavior towards specific events at the cellular (microscale) and macromolecular (nanoscale) level. In this context, the electrospinning technique is useful to generate fiber assemblies having peculiar fiber diameters at the nanoscale and patterned by unidirectional ways, to facilitate neurite extension via contact guidance. Following a bio-mimetic approach, fully aligned polycaprolactone fibers blended with gelatin macromolecules have been fabricated as potential bioactive substrate for nerve regeneration. Morphological and topographic aspects of electrospun fibers assessed by SEM/AFM microscopy supported by image analyses elaboration allow estimating an increase of fully aligned fibers from 5 to 39 % as collector rotating rate increases from 1,000 to 3,000 rpm. We verify that fully alignment of fibers positively influences in vitro response of hMSC and PC-12 cells in neurogenic way. Immunostaining images show that the presence of topological defects, i.e., kinks—due to more frequent fiber crossing—in the case of randomly organized fiber assembly concurs to interfere with proper neurite outgrowth. On the contrary, fully aligned fibers without kinks offer a more efficient contact guidance to direct the orientation of nerve cells along the fibers respect to randomly organized ones, promoting a high elongation of neurites at 7 days and the formation of bipolar extensions. So, this confirms that the topological cue of fully alignment of fibers elicits a favorable environment for nerve regeneration.     

Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.     

Report on inaugural workshop RSA ReHi-Network ‘Interdisciplinary connections between history & regional studies’*

The RSA Research Network on Regional Economic and Policy History (ReHi) aims to investigate the role of the historic perspective on regional studies through a series of events. During the inaugural two-day workshop, held in London in April 2017, the participants highlighted historical methodologies and approaches that establish a common thread in the various regional disciplines. They defined interdisciplinary connections that need to be addressed to overcome the discontinuous dialogue among researchers of regional studies and history. The research papers that were presented at the conference focused on improving methodologies, analysing economic strategies, developing techniques, and understanding policy development. The workshop aimed at establishing the foundation for a common research framework to improve the scientific debate and provide impact on regional policy regulations.