A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet to support long-term ...metabolic and heart health. Here, dose dependent and clinically relevant cell-based activities of pure C15:0 (FA15TM) were compared to eicosapentaenoic acid (EPA), a leading omega-3 fatty acid, as well as to an additional 4,500 compounds. These studies included 148 clinically relevant biomarkers measured across 12 primary human cell systems, mimicking various disease states, that were treated with C15:0 at four different concentrations (1.9 to 50 μM) and compared to non-treated control systems. C15:0 was non-cytotoxic at all concentrations and had dose dependent, broad anti-inflammatory and antiproliferative activities involving 36 biomarkers across 10 systems. In contrast, EPA was cytotoxic to four cell systems at 50 μM. While 12 clinically relevant activities were shared between C15:0 and EPA at 17 μM, C15:0 had an additional 28 clinically relevant activities, especially anti-inflammatory, that were not present in EPA. Further, at 1.9 and 5.6 μM, C15:0 had cell-based properties similar to bupropion (Pearson's scores of 0.78), a compound commonly used to treat depression and other mood disorders. At 5.6 μM, C15:0 mimicked two antimicrobials, climabazole and clarithromycin (Pearson's scores of 0.76 and 0.75, respectively), and at 50 μM, C15:0 activities matched that of two common anti-cancer therapeutics, gemcitabine and paclitaxel (Pearson's scores of 0.77 and 0.74, respectively). In summary, C15:0 had dose-dependent and clinically relevant activities across numerous human cell-based systems that were broader and safer than EPA, and C15:0 activities paralleled common therapeutics for mood disorders, microbial infections, and cancer. These studies further support the emerging role of C15:0 as an essential fatty acid.
A summary of the latest evidence‐based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, ...and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes‐related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non‐nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted ‘GRADE’ methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.
What's new?
These updated guidelines, based on recently published studies, provide evidence‐based recommendations for the prevention and management of diabetes.
The focus is on food, rather than nutrients, and an individualized, flexible approach to nutritional management is recommended.
New guidelines for remission of Type 2 diabetes and considerations for ethnic minorities are included.
Guidelines are assessed using adapted ‘GRADE’ methodology.
The potential ecological impact of disinfection by-products (DBPs) present in chlorinated wastewater effluents is not well understood. In this study, the chlorinated effluent of traditional ...wastewater treatment plants (WWTPs) and advanced water reclamation plants (AWRPs) supplying highly-treated recycled water were analyzed for nitrosamines and trihalomethanes (THMs), and a battery of bioassays conducted to assess effluent toxicity. An increase in general toxicity from DBPs was revealed for all wastewaters studied using an in vitro bioluminescence assay. Examples of androgenic activity and estrogenic activity arising from DBPs at specific sampling sites were also observed. The in vivo model (Artemia franciscana) was generally not adversely affected by exposure to DBPs from any of the chlorinated wastewaters studied. The observed toxicity could not be related to the concentrations of THMs and nitrosamines present, indicating that DBPs not monitored in this study were responsible for this. This work highlights the complexity of DBPs mixtures formed in chlorinated wastewaters, illustrating that toxicity of wastewater DBPs cannot be predicted by chemical monitoring of THMs and nitrosamines. The results suggest bioassays may be particularly useful monitoring tools in assessing toxicity arising from DBPs of these complex waters. The research concludes that DBPs formed in the chlorinated wastewaters studied can be toxic and may have a deleterious impact on aquatic organisms that are exposed to them, and therefore, that chlorination or chlorination/dechlorination may not be adequate treatment strategies for the protection of receiving waters. Chlorinated wastewater toxicity (from DBPs) is not well-understood in the Australian context, and this study serves to advise regulators on this issue.
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► DBPs in chlorinated wastewaters contribute to effluent general toxicity. ► Toxicity from DBPs in chlorinated wastewater was not correlated to monitored DBPs. ► Androgenic activity consistently arose upon chlorination of one wastewater studied. ► Estrogenic activity of wastewaters increased or decreased with chlorination. ► Wastewater genotoxicity was not attributed to chlorination by-product formation.
Neuroethology of primate social behavior Chang, Steve W. C.; Brent, Lauren J. N.; Adams, Geoffrey K. ...
Proceedings of the National Academy of Sciences - PNAS,
06/2013, Letnik:
110, Številka:
Supplement 2
Journal Article
Recenzirano
Odprti dostop
A neuroethological approach to human and nonhuman primate behavior and cognition predicts biological specializations for social life. Evidence reviewed here indicates that ancestral mechanisms are ...often duplicated, repurposed, and differentially regulated to support social behavior. Focusing on recent research from nonhuman primates, we describe how the primate brain might implement social functions by coopting and extending preexisting mechanisms that previously supported nonsocial functions. This approach reveals that highly specialized mechanisms have evolved to decipher the immediate social context, and parallel circuits have evolved to translate social perceptual signals and nonsocial perceptual signals into partially integrated social and nonsocial motivational signals, which together inform general-purpose mechanisms that command behavior. Differences in social behavior between species, as well as between individuals within a species, result in part from neuromodulatory regulation of these neural circuits, which itself appears to be under partial genetic control. Ultimately, intraspecific variation in social behavior has differential fitness consequences, providing fundamental building blocks of natural selection. Our review suggests that the neuroethological approach to primate behavior may provide unique insights into human psychopathology.
Fibrin and D-dimer bind to monomeric GPVI Onselaer, Marie-Blanche; Hardy, Alexander T.; Wilson, Clare ...
Blood advances,
08/2017, Letnik:
1, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Fibrin has recently been shown to activate platelets through the immunoglobulin receptor glycoprotein VI (GPVI). In the present study, we show that spreading of human platelets on fibrin is abolished ...in patients deficient in GPVI, confirming that fibrin activates human platelets through the immunoglobulin receptor. Using a series of proteolytic fragments, we show that D-dimer, but not the E fragment of fibrin, binds to GPVI and that immobilized D-dimer induces platelet spreading through activation of Src and Syk tyrosine kinases. In contrast, when platelets are activated in suspension, soluble D-dimer inhibits platelet aggregation induced by fibrin and collagen, but not by a collagen-related peptide composed of a repeat GPO sequence or by thrombin. Using surface plasmon resonance, we demonstrate that fibrin binds selectively to monomeric GPVI with a KD of 302 nM, in contrast to collagen, which binds primarily to dimeric GPVI. These results establish GPVI as the major signaling receptor for fibrin in human platelets and provide evidence that fibrin binds to a distinct configuration of GPVI. This indicates that it may be possible to develop agents that selectively block the interaction of fibrin but not collagen with the immunoglobulin receptor. Such agents are required to establish whether selective targeting of either interaction has the potential to lead to development of an antithrombotic agent with a reduced effect on bleeding relative to current antiplatelet drugs.
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•GPVI is the major signaling receptor for fibrin in human platelets; the GPVI binding site is located in the fibrin D-dimer region.•D-dimer blocks platelet aggregation by fibrin and collagen but not by a collagen-related peptide, suggesting a distinct binding epitope.
Von Economo neurons (VENs) are a recently evolved cell type which may be involved in the fast intuitive assessment of complex situations. As such, they could be part of the circuitry supporting human ...social networks. We propose that the VENs relay an output of fronto-insular and anterior cingulate cortex to the parts of frontal and temporal cortex associated with theory-of-mind, where fast intuitions are melded with slower, deliberative judgments. The VENs emerge mainly after birth and increase in number until age 4 yrs. We propose that in autism spectrum disorders the VENs fail to develop normally, and that this failure might be partially responsible for the associated social disabilities that result from faulty intuition.
Methods: Ten women’s water polo players performed standard drills of swimming, blocking, low and high intensity throwing under training conditions. Data were partitioned into a training and a test ...set and used to form a decision tree algorithm. Discussion: Water polo external training load monitoring can inform training load prescription according to progressive overload principles.
The presence of bromide (Br−) and iodide (I−) in source waters leads to the formation of brominated and iodinated disinfection by-products (DBPs), which are often more toxic than their chlorinated ...analogues. The increasing scarcity of water resources in Australia is leading to use of impaired and alternative water supplies with high bromide and iodide levels, which may result in the production of more brominated and iodinated DBPs. This review aims to provide a summary of research into bromide and iodide removal from drinking water sources. Bromide and iodide removal techniques have been broadly classified into three categories, namely; membrane, electrochemical and adsorptive techniques. Reverse osmosis, nanofiltration and electrodialysis membrane techniques are reviewed. The electrochemical techniques discussed are electrolysis, capacitive deionization and membrane capacitive deionization. Studies on bromide and iodide removal using adsorptive techniques including; layered double hydroxides, impregnated activated carbons, carbon aerogels, ion exchange resins, aluminium coagulation and soils are also assessed. Halide removal techniques have been compared, and areas for future research have been identified.
► Membrane techniques are efficient at removing halide DBP precursors from water. ► Electrochemical techniques remove halides but do not effectively remove organic DBP precursors. ► Adsorptive halide removal techniques are difficult with competing anions present.
Abstract ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, ...differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer. Gain and loss of function cellular studies indicate the inhibitory effect of FLI1 expression on cellular growth, migration, and invasion. Using Fli1 mutant mice and both a transgenic murine breast cancer model and an orthotopic injection of syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated tumor growth. Global expression analysis and RNA-Seq data from an invasive human breast cancer cell line with over expression of either FLI1 and another ETS gene, PDEF, shows changes in several cellular pathways associated with cancer, such as the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This study demonstrates a novel role for FLI1 in epithelial cells. In addition, these results reveal that FLI1 down-regulation in breast cancer may promote tumor progression.
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