Sensing of glucose in the brain.

The brain, and in particular the hypothalamus and brainstem, have been recognized for decades as important centers for the homeostatic control of feeding, energy expenditure, and glucose homeostasis. These structures contain neurons and neuronal circuits that may be directly or indirectly activated or inhibited by glucose, lipids, or amino acids. The detection by neurons of these nutrient cues may become deregulated, and possibly cause metabolic diseases such as obesity and diabetes. Thus, there is a major interest in identifying these neurons, how they respond to nutrients, the neuronal circuits they form, and the physiological function they control. Here I will review some aspects of glucose sensing by the brain. The brain is responsive to both hyperglycemia and hypoglycemia, and the glucose sensing cells involved are distributed in several anatomical sites that are connected to each other. These eventually control the activity of the sympathetic or parasympathetic nervous system, which regulates the function of peripheral organs such as liver, white and brown fat, muscle, and pancreatic islets alpha and beta cells. There is now evidence for an extreme diversity in the sensing mechanisms used, and these will be reviewed.

SCAP is required for timely and proper myelin membrane synthesis.

Myelination requires a massive increase in glial cell membrane synthesis. Here, we demonstrate that the acute phase of myelin lipid synthesis is regulated by sterol regulatory element-binding protein (SREBP) cleavage activation protein (SCAP), an activator of SREBPs. Deletion of SCAP in Schwann cells led to a loss of SREBP-mediated gene expression involving cholesterol and fatty acid synthesis. Schwann cell SCAP mutant mice show congenital hypomyelination and abnormal gait. Interestingly, aging SCAP mutant mice showed partial regain of function; they exhibited improved gait and produced small amounts of myelin indicating a slow SCAP-independent uptake of external lipids. Accordingly, extracellular lipoproteins partially rescued myelination by SCAP mutant Schwann cells. However, SCAP mutant myelin never reached normal thickness and had biophysical abnormalities concordant with abnormal lipid composition. These data demonstrate that SCAP-mediated regulation of glial lipogenesis is key to the proper synthesis of myelin membrane, and provide insight into abnormal Schwann cell function under conditions affecting lipid metabolism.

Biochemical analysis of female mice urine with reference to endocrine function: a key tool for estrus detection.

Species-specific chemical signals released through urine, sweat, saliva and feces are involved in communication between animals. Urinary biochemical constituents along with pheromones may contribute to variation across reproductive cycles and facilitate to estrus detection. Hence, the present study was designed to analyze such biochemical profiles, such as proteins, carbohydrates, lipids, fatty acids, in response with steroid hormones such as estradiol and progesterone. The experimental groups were normal, prepubertal, ovariectomized, and ovariectomized with estrogentreated female mice. In normal mice, the protein and lipid concentrations in urine were significantly higher in proestrus and estrus phases and the quantity of fatty acids was also comparatively higher in estrus. Furthermore, certain fatty acids, namely tridecanoic, palmitic and oleic acids, were present during proestrus and estrus phases, but were exclusively absent in ovariectomized mice. However, the carbohydrate level was equally maintained throughout the four phases of estrous cycle. For successful communication, higher concentrations of protein and specific fatty acids in estrus are directly involved. The significant increase in estradiol at estrus and progesterone at metestrus seems to be of greater importance in the expression pattern of biochemical constituents and may play a notable role in estrous cycle regulation. Thus, we conclude that the variations observed in the concentration of the biochemical constituents depend on the phase of the reproductive cycle as well as hormonal status of animals. The appearance of protein and specific fatty acids during estrus phase raises the possibility to use these as a urinary indicators for estrus detection.

Interest of qualitative and quantitative profiling of endocannabinoids for evaluation of their implication in drug addiction process

Introduction: In the middle of the 90's, the discovery of endogenous ligands for cannabinoid receptors opened a new era in this research field. Amides and esters of arachidonic acid have been identified as these endogenous ligands. Arachidonoylethanolamide (anandamide or AEA) and 2-Arachidonoylglycerol (2-AG) seem to be the most important of these lipid messengers. In addition, virodhamine (VA), noladin ether (2-AGE), and N-arachidonoyl dopamine (NADA) have been shown to bind to CB receptors with varying affinities. During recent years, it has become more evident that the EC system is part of fundamental regulatory mechanisms in many physiological processes such as stress and anxiety responses, depression, anorexia and bulimia, schizophrenia disorders, neuroprotection, Parkinson disease, anti-proliferative effects on cancer cells, drug addiction, and atherosclerosis. Aims: This work presents the problematic of EC analysis and the input of Information Dependant Acquisition based on hybrid triple quadrupole linear ion trap (QqQLIT) system for the profiling of these lipid mediators. Methods: The method was developed on a LC Ultimate 3000 series (Dionex, Sunnyvale, CA, USA) coupled to a QTrap 4000 system (Applied biosystems, Concord, ON, Canada). The ECs were separated on an XTerra C18 MS column (50 × 3.0 mm i.d., 3.5 μm) with a 5 min gradient elution. For confirmatory analysis, an information-dependant acquisition experiment was performed with selected reaction monitoring (SRM) as survey scan and enhanced produced ion (EPI) as dependant scan. Results: The assay was found to be linear in the concentration range of 0.1-5 ng/mL for AEA, 0.3-5 ng/mL for VA, 2-AGE, and NADA and 1-20 ng/mL for 2-AG using 0.5 mL of plasma. Repeatability and intermediate precision were found less than 15% over the tested concentration ranges. Under non-pathophysiological conditions, only AEA and 2-AG were actually detected in plasma with concentration ranges going from 104 to 537 pg/mL and from 2160 to 3990 pg/mL respectively. We have particularly focused our scopes on the evaluation of EC level changes in biological matrices through drug addiction and atherosclerosis processes. We will present preliminary data obtained during pilot study after administration of cannabis on human patients. Conclusion: ECs have been shown to play a key role in regulation of many pathophysiological processes. Medical research in these different fields continues to growth in order to understand and to highlight the predominant role of EC in the CNS and peripheral tissues signalisation. The profiling of these lipids needs to develop rapid, highly sensitive and selective analytical methods.

The glycoinositol-phospholipids of Phytomonas.

The Phytomonas spp. are trypanosomatid parasites of plants. A polar glycolipid fraction of a Phytomonas sp., isolated from the plant Euphorbia characias and grown in culture, was fractionated into four major glycolipid species (Phy 1-4). The glycolipids were analysed by chemical and enzymic modifications, composition and methylation analyses, electrospray mass spectrometry and microsequencing after HNO2 deamination and NaB3H4 reduction. The water-soluble headgroup of the Phy2 glycolipid was also analysed by 1H NMR. All four glycolipids were shown to be glycoinositol-phospholipids (GIPLs) with phosphatidylinositol (PI) moieties containing the fully saturated alkylacylglycerol lipids 1-O-hexadecyl-2-O-palmitoylglycerol and 1-O-hexadecyl-2-O-stearoylglycerol. The structures of the Phy 1-4 GIPLs are: Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, Glc alpha 1-2(NH2-CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, [formula: see text] Glc alpha 1-2(NH2CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2-CH2CH2-HPO4-)GlcN alpha 1-6PI [formula: see text] and Glc alpha 1-2Glc alpha 1-2(NH2CH2-CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2CH2CH2-HPO4-)-GlcN alpha 1-6PI. [formula: see text] The Phytomonas GIPLs represent a novel series of structures. This is the first description of the chemical structure of cell-surface molecules of this plant pathogen. The Phytomonas GIPLs are compared with those of other trypanosomatid parasites and are discussed with respect to trypanosomatid phylogenetic relationships.

Modulation of fructose metabolism by dietary factors

High fructose consumption is associated with obesity and characteristics of metabolic syndrome. This includes insulin resistance, dyslipidemia, type II diabetes and hepatic steatosis, the hepatic component of metabolic syndrome. Short term high fructose consumption in healthy humans is considered as a study model to increase intrahepatocellular lipids (IHCL). Protein supplementation added to a short term high fructose diet exerts a protective role on hepatic fat accumulation. Fructose disposal after an acute fructose load is well established. However, fructose disposal is usually studied when a high intake of fructose is ingested. Interaction of fructose with other macronutrients on fructose disposal is not clearly established. We wanted to assess how fructose disposal is modulated with nutritional factors. For the first study, we addressed the question of how would essential amino acid (EAA) supplemented to a high fructose diet have an impact on hepatic fat accumulation? We tried to distinguish which metabolic pathways were responsible for the increase in IHCL induced by high fructose intake and how those pathways would be modulated by EAA. After 6 days of hypercaloric high fructose diet, we observed, as expected an increase in IHCL modulated by an increase in VLDL-triglycerides and an increase in VLDL-13C-palmitate production. When adding a supplementation in EAA, we observed a decrease in IHCL but we could not define which mechanism was responsible for this process. With the second study, we were interested to observe fructose disposal after a test meal that contained lipid, protein and a physiologic dose of fructose co-ingested or not with glucose. When ingested with other macronutrients, hepatic fructose disposal is similar as when ingested as pure fructose. It induced oxidation, gluconeogenesis followed by glycogen synthesis, conversion into lactate and to a minor extent by de novo lipogenesis. When co- ingested with glucose decreased fructose oxidation as well as gluconeogenesis and an increased glycogen synthesis without affecting de novo lipogenesis or lactate. We were also able to observe induction of intestinal de novo lipogenesis with both fructose and fructose co- ingested with glucose. In summary, essential amino acids supplementation blunted increase in hepatic fat content induced by a short term chronic fructose overfeeding. However, EAA failed to improve other cardiovascular risk factors. Under isocaloric condition and in the frame of an acute test meal, physiologic dose of fructose associated with other macronutrients led to the same fructose disposal as when fructose is ingested alone. When co-ingested with glucose, we observed a decrease in fructose oxidation and gluconeogenesis as well as an increased in glycogen storage without affecting other metabolic pathways. - Une consommation élevée en fructose est associée à l'obésité et aux caractéristiques du syndrome métabolique. Ces dernières incluent une résistance à l'insuline, une dyslipidémie, un diabète de type II et la stéatose hépatique, composant hépatique du syndrome métabolique. À court terme une forte consommation en fructose chez l'homme sain est considérée comme un modèle d'étude pour augmenter la teneur en graisse hépatique. Une supplémentation en protéines ajoutée à une alimentation riche en fructose de courte durée a un effet protecteur sur l'accumulation des graisses au niveau du foie. Le métabolisme du fructose après une charge de fructose aiguë est bien établi. Toutefois, ce dernier est généralement étudié quand une consommation élevée de fructose est donnée. L'interaction du fructose avec d'autres macronutriments sur le métabolisme du fructose n'est pas connue. Nous voulions évaluer la modulation du métabolisme du fructose par des facteurs nutritionnels. Pour la première étude, nous avons abordé la question de savoir quel impact aurait une supplémentation en acides aminés essentiels (AEE) associé à une alimentation riche en fructose sur l'accumulation des graisses hépatiques. Nous avons essayé de distinguer les voies métaboliques responsables de l'augmentation des graisses hépatiques induite par l'alimentation riche en fructose et comment ces voies étaient modulées par les AEE. Après 6 jours d'une alimentation hypercalorique riche en fructose, nous avons observé, comme attendu, une augmentation des graisses hépatiques modulée par une augmentation des triglycérides-VLDL et une augmentation de la production de VLDL-13C-palmitate. Lors de la supplémentation en AEE, nous avons observé une diminution des graisses hépatiques mais les mécanismes responsables de ce processus n'ont pas pu être mis en évidence. Avec la seconde étude, nous nous sommes intéressés à observer le métabolisme du fructose après un repas test contenant des lipides, des protéines et une dose physiologique de fructose co-ingéré ou non avec du glucose. Lorsque le fructose était ingéré avec les autres macronutriments, le devenir hépatique du fructose était similaire à celui induit par du fructose pur. Il a induit une oxydation, suivie d'une néoglucogenèses, une synthèse de glycogène, une conversion en lactate et dans une moindre mesure une lipogenèse de novo. Lors de la co-ngestion avec du glucose, nous avons observé une diminution de l'oxydation du fructose et de la néoglucogenèse et une augmentation de la synthèse du glycogène, sans effet sur la lipogenèse de novo ni sur le lactate. Nous avons également pu mettre en évidence que le fructose et le fructose ingéré de façon conjointe avec du glucose ont induit une lipogenèse de novo au niveau de l'intestin. En résumé, la supplémentation en acides aminés essentiels a contrecarré l'augmentation de la teneur en graisse hépatique induite par une suralimentation en fructose sur le court terme. Cependant, la supplémentation en AEE a échoué à améliorer d'autres facteurs de risque cardiovasculaires. Dans la condition isocalorique et dans le cadre d'un repas test aiguë, la dose physiologique de fructose associée à d'autres macronutriments a conduit aux mêmes aboutissants du métabolisme du fructose que lorsque le fructose est ingéré seul. Lors de la co-ngestion avec le glucose, une diminution de l'oxydation du fructose est de la néoglucogenèse est observée en parallèle à une augmentation de la synthèse de glycogène sans affecter les autres voies métaboliques.

Analysis of the beta-oxidation of trans-unsaturated fatty acid in recombinant Saccharomyces cerevisiae expressing a peroxisomal PHA synthase reveals the involvement of a reductase-dependent pathway.

The degradation of fatty acids having cis- or trans-unsaturated bond at an even carbon was analyzed in Saccharomyces cerevisiae by monitoring polyhydroxyalkanoate production in the peroxisome. Polyhydroxyalkanaote is synthesized by the polymerization of the beta-oxidation intermediates 3-hydroxy-acyl-CoAs via a bacterial polyhydroxyalkanoate synthase targeted to the peroxisome. The synthesis of polyhydroxyalkanoate in cells grown in media containing 10-cis-heptadecenoic acid was dependent on the presence of 2,4-dienoyl-CoA reductase activity as well as on Delta3,Delta2-enoyl-CoA isomerase activity. The synthesis of polyhydroxyalkanoate from 10-trans-heptadecenoic acid in mutants devoid of 2,4-dienoyl-CoA reductase revealed degradation of the trans fatty acid directly via the enoyl-CoA hydratase II activity of the multifunctional enzyme (MFE), although the level of polyhydroxyalkanoate was 10-25% to that of wild type cells. Polyhydroxyalkanoate produced from 10-trans-heptadecenoic acid in wild type cells showed substantial carbon flux through both a reductase-dependent and a direct MFE-dependent pathway. Flux through beta-oxidation was more severely reduced in mutants devoid of Delta3,Delta2-enoyl-CoA isomerase compared to mutants devoid of 2,4-dienoyl-CoA reductase. It is concluded that the intermediate 2-trans,4-trans-dienoyl-CoA is metabolized in vivo in yeast by both the enoyl-CoA hydratase II activity of the multifunctional protein and the 2,4-dienoyl-CoA reductase, and that the synthesis of the intermediate 3-trans-enoyl-CoA in the absence of the Delta3,Delta2-enoyl-CoA isomerase leads to the blockage of the direct MFE-dependent pathway in vivo.

Membrane fluidization triggers membrane remodeling which affects the thermotolerance in Escherichia coli.

Treatment of Escherichia coli with non-lethal doses of heat or benzyl alcohol (BA) causes transient membrane fluidization and permeabilization, and induces the rapid transcription of heat-shock genes in a sigma32-dependent manner. This early response is followed by a rapid adaptation (priming) of the cells to otherwise lethal elevated temperature, in strong correlation with an observed remodeling of the composition and alkyl chain unsaturation of membrane lipids. The acquisition of cellular thermotolerance in BA-primed cells is unrelated to protein denaturation and is not accompanied by the formation of major heat-shock proteins, such as GroEL and DnaK. This suggests that the rapid remodeling of membrane composition is sufficient for the short-term bacterial thermotolerance.

Absence of VLDL secretion does not affect alpha-tocopherol content in peripheral tissues

alpha-Tocopherol is a lipid-soluble antioxidant that helps to prevent oxidative damage to cellular lipids. alpha-Tocopherol is absorbed by the intestine and is taken up and retained by the liver; it is widely presumed that alpha-tocopherol is then delivered to peripheral tissues by the secretion of VLDL. To determine whether VLDL secretion is truly important for the delivery of alpha-tocopherol to peripheral tissues, we examined alpha-tocopherol metabolism in mice that lack microsomal triglyceride transfer protein (Mttp) expression in the liver and therefore cannot secrete VLDL (Mttp(Delta/Delta) mice). Mttp(Delta/Delta) mice have low plasma lipid levels and increased stores of lipids in the liver. Similarly, alpha-tocopherol levels in the plasma were lower in Mttp(Delta/Delta) mice than in controls, whereas hepatic alpha-tocopherol stores were higher. However, alpha-tocopherol levels in the peripheral tissues of Mttp(Delta/Delta) mice were nearly identical to those of control mice, suggesting that VLDL secretion is not critical for the delivery of alpha-tocopherol to peripheral tissues. When fed a diet containing deuterated alpha-tocopherol, Mttp(Delta/Delta) and control mice had similar incorporation of deuterated alpha-tocopherol into plasma and various peripheral tissues. We conclude that the absence of VLDL secretion has little effect on the stores of alpha-tocopherol in peripheral tissues, at least in the mouse.

Jasmonates and related oxylipins in plant responses to pathogenesis and herbivory.

The vigorous production of oxygenated fatty acids (oxylipins) is a characteristic response to pathogenesis and herbivory, and is often accompanied by the substantial release of small and reactive lipid-fragmentation products. Some oxylipins, most notably those of the jasmonate family, have key roles as potent regulators. Recent advances have been made in understanding oxylipin-regulated signal transduction in response to attack. Much jasmonate signaling takes place via a genetically defined signal network that is linked to the ethylene, auxin, and salicylic acid signal pathways, but a second aspect of jasmonate signaling is emerging. Some jasmonates and several newly discovered cyclopentenone lipids can activate or repress gene expression through the activities of a conserved electrophilic atom group.

Electronic monitoring of compliance to lipid-lowering therapy in clinical practice

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.

Incretins: what is known, new and controversial in 2013?

Glucagon-like peptide (GLP)-1 action involves both endocrine and neural pathways to control peripheral tissues. In diabetes the impairment of either pathway may define different subsets of patients: some may be better treated with GLP-1 receptor agonists that are more likely to directly stimulate beta-cells and extrapancreatic receptors, while others may benefit from dipeptidyl peptidase (DPP)-4 inhibitor treatments that are more likely to increase the neural gut-brain-pancreas axis. Elevated plasma concentrations of GLP-1 associated with agonist treatment or bariatric surgery also appear to exert neuroprotective effects, ameliorate postprandial and fasting lipids, improve heart physiology and protect against heart failure, thereby expanding the possible positioning of GLP-1-based therapies. However, the mechanisms behind GLP-1 secretion, the role played by proximal and distal intestinal GLP-1-producing cells as well as the molecular basis of GLP-1 resistance in diabetes are still to be ascertained. The pharmacological features distinguishing GLP-1 receptor agonists from DPP-4 inhibitors are discussed here to address their respective positions in type 2 diabetes.

The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.

Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions.

Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats.

Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Delta6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4(+)/CD8(+) T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in both ages. This alleviation may be associated with a large amount of lactoglobulin in WPI. These results thus showed a possibility that oxidized cholesterol-induced perturbations of age-related changes of lipid metabolism and immune function can be moderated by both the selection and combination of dietary protein.

'Bio-nano interactions: new tools, insights and impacts': summary of the Royal Society discussion meeting

Bio-nano interactions can be defined as the study of interactions between nanoscale entities and biological systems such as, but not limited to, peptides, proteins, lipids, DNA and other biomolecules, cells and cellular receptors and organisms including humans. Studying bio-nano interactions is particularly useful for understanding engineered materials that have at least one dimension in the nanoscale. Such materials may consist of discrete particles or nanostructured surfaces. Much of biology functions at the nanoscale; therefore, our ability to manipulate materials such that they are taken up at the nanoscale, and engage biological machinery in a designed and purposeful manner, opens new vistas for more efficient diagnostics, therapeutics (treatments) and tissue regeneration, so-called nanomedicine. Additionally, this ability of nanomaterials to interact with and be taken up by cells allows nanomaterials to be used as probes and tools to advance our understanding of cellular functioning. Yet, as a new technology, assessment of the safety of nanomaterials, and the applicability of existing regulatory frameworks for nanomaterials must be investigated in parallel with development of novel applications. The Royal Society meeting 'Bio-nano interactions: new tools, insights and impacts' provided an important platform for open dialogue on the current state of knowledge on these issues, bringing together scientists, industry, regulatory and legal experts to concretize existing discourse in science law and policy. This paper summarizes these discussions and the insights that emerged.