The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells

Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here, we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. We cultured a series of glioma cell lines (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM substrates of defined mechanical rigidity and investigated the role of ECM rigidity in regulating tumor cell structure, migration, and proliferation. On highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to values comparable with normal brain tissue, tumor cells appear rounded and fail to productively migrate. Remarkably, cell proliferation is also strongly regulated by ECM rigidity, with cells dividing much more rapidly on rigid than on compliant ECMs. Pharmacologic inhibition of nonmuscle myosin II–based contractility blunts this rigidity-sensitivity and rescues cell motility on highly compliant substrates. Collectively, our results provide support for a novel model in which ECM rigidity provides a transformative, microenvironmental cue that acts through actomyosin contractility to regulate the invasive properties of GBM tumor cells.

Rational design of artificial cellular niches for tissue engineering

Tissue Engineering is a promising emerging field that studies the intrinsic regenerative potential of the human body and uses it to restore functionality of damaged organs or tissues unable of self-healing due to illness or ageing. In order to achieve regeneration using Tissue Engineering strategies, it is first necessary to study the properties of the native tissue and determine the cause of tissue failure; second, to identify an optimum population of cells capable of restoring its functionality; and third, to design and manufacture a cellular microenvironment in which those specific cells are directed towards the desired cellular functions. The design of the artificial cellular niche has a tremendous importance, because cells will feel and respond to both its biochemical and biophysical properties very differently. In particular, the artificial niche will act as a physical scaffold for the cells, allowing their three-dimensional spatial organization; also, it will provide mechanical stability to the artificial construct; and finally, it will supply biochemical and mechanical cues to control cellular growth, migration, differentiation and synthesis of natural extracellular matrix. During the last decades, many scientists have made great contributions to the field of Tissue Engineering. Even though this research has frequently been accompanied by vast investments during extended periods of time, yet too often these efforts have not been enough to translate the advances into new clinical therapies. More and more scientists in this field are aware of the need of rational experimental designs before carrying out complex, expensive and time-consuming in vitro and in vivo trials. This review highlights the importance of computer modeling and novel biofabrication techniques as critical key players for a rational design of artificial cellular niches in Tissue Engineering.

Homologs of FT, CEN and FD respond to developmental and environmental signals affecting growth and flowering in the perennial vine kiwifruit

FLOWERING LOCUS T (FT) and CENTRORADIALIS (CEN) homologs have been implicated in regulation of growth, determinacy and flowering. The roles of kiwifruit FT and CEN were explored using a combination of expression analysis, protein interactions, response to temperature in high-chill and low-chill kiwifruit cultivars and ectopic expression in Arabidopsis and Actinidia. The expression and activity of FT was opposite from that of CEN and incorporated an interaction with a FLOWERING LOCUS D (FD)-like bZIP transcription factor. Accumulation of FT transcript was associated with plant maturity and particular stages of leaf, flower and fruit development, but could be detected irrespective of the flowering process and failed to induce precocious flowering in transgenic kiwifruit. Instead, transgenic plants demonstrated reduced growth and survival rate. Accumulation of FT transcript was detected in dormant buds and stem in response to winter chilling. In contrast, FD in buds was reduced by exposure to cold. CEN transcript accumulated in developing latent buds, but declined before the onset of dormancy and delayed flowering when ectopically expressed in kiwifruit. Our results suggest roles for FT, CEN and FD in integration of developmental and environmental cues that affect dormancy, budbreak and flowering in kiwifruit.

Cravings and Expectancies

Drug-dependent individuals commonly report craving, which is an urge to consume a substance to experience pleasure or provide relief. However, the motivation to use drugs is also influenced by the expectancies we hold about drug ingestion. Drug expectancies are among a range of internal and external cues that can elicit craving. Scientific advances in the neurobiology of reward have illuminated individual differences in the neurotransmitter systems involved in associative learning that underpin drug use motivation and expectancies. We have begun to elaborate the interrelationships of these constructs and mechanisms to inform new treatments that incorporate recent models of reward learning.

Disparate companions : tissue engineering meets cancer research

Recreating an environment that supports and promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis, and providing suitable stromal support and signalling cues are keys to successfully generating clinically useful tissues. Interestingly, those components are often subverted in the cancer setting, where aberrant angiogenesis, cellular proliferation, cell signalling and resistance to apoptosis drive malignant growth. In contrast to tissue engineering, identifying and inhibiting those pathways is a major challenge in cancer research. The recent discovery of adult tissue-specific stem cells has had a major impact on both tissue engineering and cancer research. The unique properties of these cells and their role in tissue and organ repair and regeneration hold great potential for engineering tissue-specific constructs. The emerging body of evidence implicating stem cells and progenitor cells as the source of oncogenic transformation prompts caution when using these cells for tissue-engineering purposes. While tissue engineering and cancer research may be considered as opposed fields of research with regard to their proclaimed goals, the compelling overlap in fundamental pathways underlying these processes suggests that cross-disciplinary research will benefit both fields. In this review article, tissue engineering and cancer research are brought together and explored with regard to discoveries that may be of mutual benefit.

Depression and belongingness in general and workplace contexts : a cross-lagged longitudinal investigation

Belongingness has been linked to depression. Prior studies have been cross-sectional with few addressing distinct belongingness contexts. This study used structural equation modelling to investigate cross-lagged longitudinal relationships between general belonging, workplace belonging and depressive symptoms in a community sample of 221 working adults measured at two time points three months apart. Measures were: Sense of Belonging Instrument-Psychological (SOBI-P); Psychological Sense of Organizational Membership (PSOM); Depression Anxiety Stress Scales (DASS-21); Kessler Psychological Distress Scale (K10). General belonging was predicted more strongly by depressive symptoms than by baseline general belonging, suggesting that depressive symptoms not only linger but also influence future belongingness cognitions. Neither general nor workplace belonging longitudinally predicted depressive symptoms, however cross-sectional correlations were substantial. The concurrent path between general belongingness and depressive symptoms was strong. Results are consistent with daily process studies suggesting that reduced belongingness precipitates a rapid increase in depressive symptoms which influence longer term belongingness cognitions. Congruent with interpersonal descriptions of depression such as the social-cognitive interpersonal process model, results further suggest that belongingness cognitions are the proximal antecedent of a depressive response. Practitioners should monitor both a general sense of belonging as well as perceived relational value cues in specific contexts.

Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.

The impact of users' characteristics on their ability to detect phishing emails

We investigate how email users' characteristics influence their response to phishing emails. A user generally goes through three stages of behaviour upon receiving a phishing email: suspicion of the legitimacy of the email, confirmation of its legitimacy and response by either performing the action requested in the phishing email or not. Using a mixed method approach combining experiments, surveys and semi-structured interviews, we found that a user's behaviour at each stage varies with their personal characteristics such as personality traits and ability to perceive information in an email beyond its content. We found, for example, that users who are submissive, extraverted or open tend to be less suspicious of phishing emails while users who can identify cues such as inconsistent IP address, can avoid falling victim to phishing emails. Our findings enable us to draw practical implications for educating and potentially reducing the incidence of phishing emails victimisation.

The role of active locomotion in space perception

It has been shown that active control of locomotion increases accuracy and precision of nonvisual space perception, but psychological mechanisms of this enhancement are poorly understood. The present study explored a hypothesis that active control of locomotion enhances space perception by facilitating crossmodal interaction between visual and nonvisual spatial information. In an experiment, blindfolded participants walked along a linear path under one of the following two conditions: (1) They walked by themselves following a guide rope; and (2) they were led by an experimenter. Subsequently, they indicated the walked distance by tossing a beanbag to the origin of locomotion. The former condition gave participants greater control of their locomotion, and thus represented a more active walking condition. In addition, before each trial, half the participants viewed the room in which they performed the distance perception task. The other half remained blindfolded throughout the experiment. Results showed that although the room was devoid of any particular cues for walked distances, visual knowledge of the surroundings improved the precision of nonvisual distance perception. Importantly, however, the benefit of preview was observed only when participants walked more actively. This indicates that active control of locomotion allowed participants to better utilize their visual memory of the environment for perceiving nonvisually encoded distance, suggesting that active control of locomotion served as a catalyst for integrating visual and nonvisual information to derive spatial representations of higher quality.

"What" versus "how" in nonvisual whole-body movement

Dissociable processes for conscious perception (“what” processing) and guidance of action (“how” processing) have been identified in visual, auditory, and somatosensory systems. The present study was designed to find similar dissociation within whole-body movements in which the presence of vestibular information creates a unique perceptual condition. In two experiments, blindfolded participants walked along a linear path and specified the walked distance by verbally estimating it (“what” measure) and by pulling a length of tape that matched the walked distance (“how” measure). Although these two measures yielded largely comparable responses under a normal walking condition, variability in verbal estimates showed a qualitatively different pattern from that in tape-pulling when sensory input into walking was altered by having participants wear a heavy backpack. This suggests that the “what” versus “how” dissociation exists in whole-body movements as well, supporting a claim that it is a general principle with which perceptual systems are organized.

Three social car visions to improve driver behaviour

The social cost of road injury and fatalities is still unacceptable. The driver is often mainly responsible for road crashes, therefore changing the driver behaviour is one of the most important and most challenging priority in road transport. This paper presents three innovative visions that articulate the potential of using Vehicle to Vehicle (V2V) communication for supporting the exchange of social information amongst drivers. We argue that there could be tremendous benefits in socialising cars to influence human driving behaviours for the better and that this aspect is still relevant in the age of looming autonomous cars. Our visions provide theoretical grounding how V2V infrastructure and emerging human–machine interfaces (HMI) could persuade drivers to: (i) adopt better (e.g. greener) driving practices, (ii) reduce drivers aggressiveness towards pro-social driving behaviours, and (iii) reduce risk-taking behaviour in young, particularly male, adults. The visions present simple but powerful concepts that reveal ‘good’ aspects of the driver behaviour to other drivers and make them contagious. The use of self-efficacy, social norms, gamification theories and social cues could then increase the likelihood of a widespread adoption of such ‘good’ driving behaviours.

The influence of maternal infant feeding practices and beliefs on the expression of food neophobia in toddlers

Food neophobia is a highly heritable trait characterized by the rejection of foods that are novel or unknown and potentially limits dietary variety, with lower intake and preference particularly for fruits and vegetables. Understanding non-genetic (environmental) factors that may influence the expression of food neophobia is essential to improving children’s consumption of fruits and vegetables and encouraging the adoption of healthier diets. The aim of this study was to examine whether maternal infant feeding beliefs (at four months) were associated with the expression of food neophobia in toddlers and whether controlling feeding practices mediated this relationship. Participants were 244 first-time mothers (M = 30.4, SD = 5.1 years) allocated to the control group of the NOURISH randomized controlled trial. The relationships between infant feeding beliefs (Infant Feeding Questionnaire) at four months and controlling child feeding practices (Child Feeding Questionnaire) and food neophobia (Child Food Neophobia Scale) at 24 months were tested using correlational and multiple linear regression models (adjusted for significant covariates). Higher maternal Concern about infant under-eating and becoming underweight at four months was associated with higher child food neophobia at two years. Similarly, lower Awareness of infant hunger and satiety cues was associated with higher child food neophobia. Both associations were significantly mediated by mothers’ use of Pressure to eat. Intervening early to promote positive feeding practices to mothers may help reduce the use of controlling practices as children develop. Further research that can further elucidate the bi-directional nature of the mother-child feeding relationship is still required.

Planning to Learn : Creating and Using a Personal Planner with Young People on the Autism Spectrum

Late intervention often means that young people on the autism spectrum appear to act on impulse, seem disorganized, or fail to learn from past experiences. In this practical, effective resource, the authors share tried and tested techniques for creating and using a personal planner to help individuals on the autism spectrum to develop independence. "Planning to Learn" is split into three parts. The first part guides adults in helping young people to make sense of the world and to develop and practise coping strategies for any given situation. The authors also explain how simple visual and verbal cues can help people to cope successfully in stressful situations. The second part provides worksheets for the young person to complete to learn how to use plans in different situations, for example staying calm when waiting for a doctor, or coping with a change in the school timetable. Each individual makes a unique planner with procedures to refer to, such as responding to pressure, calming down, being organised, and being around people. The third part includes useful cards, schedules and plans for photocopying and including in the planner. This illustrated photocopiable workbook is packed with guidance, support and helpful notes for those new to, or experienced in, working with children and young people with ASD. It can be used within educational and community settings or at home.

NESSTI : norms for environmental sound stimuli

In this paper we provide normative data along multiple cognitive and affective variable dimensions for a set of 110 sounds, including living and manmade stimuli. Environmental sounds are being increasingly utilized as stimuli in the cognitive, neuropsychological and neuroimaging fields, yet there is no comprehensive set of normative information for these type of stimuli available for use across these experimental domains. Experiment 1 collected data from 162 participants in an on-line questionnaire, which included measures of identification and categorization as well as cognitive and affective variables. A subsequent experiment collected response times to these sounds. Sounds were normalized to the same length (1 second) in order to maximize usage across multiple paradigms and experimental fields. These sounds can be freely downloaded for use, and all response data have also been made available in order that researchers can choose one or many of the cognitive and affective dimensions along which they would like to control their stimuli. Our hope is that the availability of such information will assist researchers in the fields of cognitive and clinical psychology and the neuroimaging community in choosing well-controlled environmental sound stimuli, and allow comparison across multiple studies.

Cortical organization of environmental sounds by attribute

Semantic knowledge is supported by a widely distributed neuronal network, with differential patterns of activation depending upon experimental stimulus or task demands. Despite a wide body of knowledge on semantic object processing from the visual modality, the response of this semantic network to environmental sounds remains relatively unknown. Here, we used fMRI to investigate how access to different conceptual attributes from environmental sound input modulates this semantic network. Using a range of living and manmade sounds, we scanned participants whilst they carried out an object attribute verification task. Specifically, we tested visual perceptual, encyclopedic, and categorical attributes about living and manmade objects relative to a high-level auditory perceptual baseline to investigate the differential patterns of response to these contrasting types of object-related attributes, whilst keeping stimulus input constant across conditions. Within the bilateral distributed network engaged for processing environmental sounds across all conditions, we report here a highly significant dissociation within the left hemisphere between the processing of visual perceptual and encyclopedic attributes of objects.