The effect of silica nanoparticle-modified surfaces on cell morphology, cytoskeletal organization and function

Chemical and morphological characteristics of a biomaterial surface are thought to play an important role in determining cellular differentiation and apoptosis. In this report, we investigate the effect of nanoparticle (NP) assemblies arranged on a flat substrate on cytoskeletal organization, proliferation and metabolic activity on two cell types, Bovine aortic endothelial cells (BAECs) and mouse calvarial preosteoblasts (MC3T3-E1). To vary roughness without altering chemistry, glass substrates were coated with monodispersed silica nanoparticles of 50, 100 and 300 nm in diameter. The impact of surface roughness at the nanoscale on cell morphology was studied by quantifying cell spreading, shape, cytoskeletal F-actin alignment, and recruitment of focal adhesion complexes (FAC) using image analysis. Metabolic activity was followed using a thiazolyl blue tetrazolium bromide assay. In the two cell types tested, surface roughness introduced by nanoparticles had cell type specific effects on cell morphology and metabolism. While BAEC on NP-modified substrates exhibited smaller cell areas and fewer focal adhesion complexes compared to BAEC grown on glass, MC3T3-E1 cells in contrast exhibited larger cell areas on NP-modified surfaces and an increased number of FACs, in comparison to unmodified glass. However, both cell types on 50 nm NP had the highest proliferation rates (comparable to glass control) whereas cells grown on 300 nm NP exhibited inhibited proliferation. Interestingly, for both cell types surface roughness promoted the formation of long, thick F-actin fibers, which aligned with the long axis of each cell. These findings are consistent with our earlier result that osteogenic differentiation of human mesenchymal progenitor cells is enhanced on NP-modified surfaces. Our finding that nanoroughness, as imparted by nanoparticle assemblies, effects cellular processes in a cell specific manner, can have far reaching consequences on the development of smart biomaterials especially for directing stem cell differentiation

Effort Perception is Made More Accurate with More Effort and When Cooperating with Slackers

Recent research on the conditions that facilitate cooperation is limited by a factor that has yet to be established: the accuracy of effort perception. Accuracy matters because the fitness of cooperative strategies depends not just on being able to perceive others' effort but to perceive their true effort. In an experiment using a novel effort-tracker methodology, we calculate the accuracy of human effort perceptions and show that accuracy is boosted by more absolute effort (regardless of relative effort) and when cooperating with a "slacker" rather than an "altruist". A formal model shows how such an effort-prober strategy is likely to be an adaptive solution because it gives would-be collaborators information on when to abort ventures that are not in their interest and opt for ones that are. This serves as a precautionary measure against systematic exploitation by extortionist strategies and a descent into uncooperativeness. As such, it is likely that humans have a bias to minimize mistakes in effort perception that would commit them to a disadvantageous effort-reward relationship. Overall we find support for the idea that humans have evolved smart effort detection systems that are made more accurate by those contexts most relevant for cooperative tasks

Signal Detection on the Battlefield: Priming Self-Protection vs. Revenge-Mindedness Differentially Modulates the Detection of Enemies and Allies

Detecting signs that someone is a member of a hostile outgroup can depend on very subtle cues. How do ecology-relevant motivational states affect such detections? This research investigated the detection of briefly-presented enemy (versus friend) insignias after participants were primed to be self-protective or revenge-minded. Despite being told to ignore the objectively nondiagnostic cues of ethnicity (Arab vs. Western/European), gender, and facial expressions of the targets, both priming manipulations enhanced biases to see Arab males as enemies. They also reduced the ability to detect ingroup enemies, even when these faces displayed angry expressions. These motivations had very different effects on accuracy, however, with self-protection enhancing overall accuracy and revenge-mindedness reducing it. These methods demonstrate the importance of considering how signal detection tasks that occur in motivationally-charged environments depart from results obtained in conventionally motivationally-inert laboratory settings.National Institute of Mental Health (U.S.) (Grant MH64734)U.S. Army Research Institute for the Behavioral and Social Sciences (Grant W74V8H-05-K-0003)National Science Foundation (U.S.) (Grant BCS-0642873

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Reduced Fertility in Patients' Families Is Consistent with the Sexual Selection Model of Schizophrenia and Schizotypy

BACKGROUND: Schizophrenia is a mental disorder marked by an evolutionarily puzzling combination of high heritability, reduced reproductive success, and a remarkably stable prevalence. Recently, it has been proposed that sexual selection may be crucially involved in the evolution of schizophrenia. In the sexual selection model (SSM) of schizophrenia and schizotypy, schizophrenia represents the negative extreme of a sexually selected indicator of genetic fitness and condition. Schizotypal personality traits are hypothesized to increase the sensitivity of the fitness indicator, thus conferring mating advantages on high-fitness individuals but increasing the risk of schizophrenia in low-fitness individuals; the advantages of successful schzotypy would be mediated by enhanced courtship-related traits such as verbal creativity. Thus, schizotypy-increasing alleles would be maintained by sexual selection, and could be selectively neutral or even beneficial, at least in some populations. However, most empirical studies find that the reduction in fertility experienced by schizophrenic patients is not compensated for by increased fertility in their unaffected relatives. This finding has been interpreted as indicating strong negative selection on schizotypy-increasing alleles, and providing evidence against sexual selection on schizotypy. METHODOLOGY: A simple mathematical model is presented, showing that reduced fertility in the families of schizophrenic patients can coexist with selective neutrality of schizotypy-increasing alleles, or even with positive selection on schizotypy in the general population. If the SSM is correct, studies of patients' families can be expected to underestimate the true fertility associated with schizotypy. SIGNIFICANCE: This paper formally demonstrates that reduced fertility in the families of schizophrenic patients does not constitute evidence against sexual selection on schizotypy-increasing alleles. Futhermore, it suggests that the fertility estimates derived from extant studies may be biased to an unknown extent. These results have important implications for the evolutionary genetics of psychosis

The Good, the Bad, and the Rare: Memory for Partners in Social Interactions

For cooperation to evolve via direct reciprocity, individuals must track their partners' behavior to avoid exploitation. With increasing size of the interaction group, however, memory becomes error prone. To decrease memory effort, people could categorize partners into types, distinguishing cooperators and cheaters. We explored two ways in which people might preferentially track one partner type: remember cheaters or remember the rare type in the population. We assigned participants to one of three interaction groups which differed in the proportion of computer partners' types (defectors rare, equal proportion, or cooperators rare). We extended research on both hypotheses in two ways. First, participants experienced their partners repeatedly by interacting in Prisoner's Dilemma games. Second, we tested categorization of partners as cooperators or defectors in memory tests after a short and long retention interval (10 min and 1 week). Participants remembered rare partner types better than they remembered common ones at both retention intervals. We propose that the flexibility of responding to the environment suggests an ecologically rational memory strategy in social interactions

New physiological activities of myosuppressin, sulfakinin and NVP-like peptide in Zophobas atratus beetle

Three neuropeptides Zopat-MS-2 (pEDVDHVFLRFa), Zopat-SK-1 (pETSDDYGHLRFa) and Zopat-NVPL-4trunc. (GRWGGFA), recently isolated from the neuroendocrine system of the Zophobas atratus beetle, were tested for their myotropic and hyperglycaemic activities in this species. These peptides exerted differentiated dose-dependent and tissue specific physiological effects. Zopat-MS-2 inhibited contractions of the isolated heart, ejaculatory duct, oviduct and hindgut of adult beetles and induced bimodal effects in the heart contractile activity of pupae in vivo. It also increased the haemolymph free sugar level in larvae of this species, apart from myotropic activity. Zopat-SK-1 showed myostimulatory action on the isolated hindgut of the adult beetles, but it decreased contractions of the heart, ejaculatory duct and oviduct. Injections of this peptide at a dose of 2 μg also caused delayed cardioinhibitory effects on the heartbeat of the pupae. Together with the ability to increase free sugar level in the haemolymph of larvae these were new physiological activities of sulfakinins in insects. Zopat-NVPL-4trunc. inhibited the muscle contractions of the two organs: hindgut and ejaculatory duct but it was inactive on the oviduct and the heart of the adult beetles. This peptide also increased free sugar level concentration in the haemolymph of Z. atratus larvae. These physiological actions are the first biological activities discovered for this group of the insect peptides. The present work showed pleiotropic activity of three neuropeptides and indicates that the visceral muscle contractions and the haemolymph sugar homeostasis in Z. atratus are regulated by complex mechanisms

A Simple Artificial Life Model Explains Irrational Behavior in Human Decision-Making

Although praised for their rationality, humans often make poor decisions, even in simple situations. In the repeated binary choice experiment, an individual has to choose repeatedly between the same two alternatives, where a reward is assigned to one of them with fixed probability. The optimal strategy is to perseverate with choosing the alternative with the best expected return. Whereas many species perseverate, humans tend to match the frequencies of their choices to the frequencies of the alternatives, a sub-optimal strategy known as probability matching. Our goal was to find the primary cognitive constraints under which a set of simple evolutionary rules can lead to such contrasting behaviors. We simulated the evolution of artificial populations, wherein the fitness of each animat (artificial animal) depended on its ability to predict the next element of a sequence made up of a repeating binary string of varying size. When the string was short relative to the animats’ neural capacity, they could learn it and correctly predict the next element of the sequence. When it was long, they could not learn it, turning to the next best option: to perseverate. Animats from the last generation then performed the task of predicting the next element of a non-periodical binary sequence. We found that, whereas animats with smaller neural capacity kept perseverating with the best alternative as before, animats with larger neural capacity, which had previously been able to learn the pattern of repeating strings, adopted probability matching, being outperformed by the perseverating animats. Our results demonstrate how the ability to make predictions in an environment endowed with regular patterns may lead to probability matching under less structured conditions. They point to probability matching as a likely by-product of adaptive cognitive strategies that were crucial in human evolution, but may lead to sub-optimal performances in other environments

The development of cross-cultural recognition of vocal emotion during childhood and adolescence

Humans have an innate set of emotions recognised universally. However, emotion recognition also depends on socio-cultural rules. Although adults recognise vocal emotions universally, they identify emotions more accurately in their native language. We examined developmental trajectories of universal vocal emotion recognition in children. Eighty native English speakers completed a vocal emotion recognition task in their native language (English) and foreign languages (Spanish, Chinese, and Arabic) expressing anger, happiness, sadness, fear, and neutrality. Emotion recognition was compared across 8-to-10, 11-to-13-year-olds, and adults. Measures of behavioural and emotional problems were also taken. Results showed that although emotion recognition was above chance for all languages, native English speaking children were more accurate in recognising vocal emotions in their native language. There was a larger improvement in recognising vocal emotion from the native language during adolescence. Vocal anger recognition did not improve with age for the non-native languages. This is the first study to demonstrate universality of vocal emotion recognition in children whilst supporting an “in-group advantage” for more accurate recognition in the native language. Findings highlight the role of experience in emotion recognition, have implications for child development in modern multicultural societies and address important theoretical questions about the nature of emotions