Rho GTPases mediate the mechanosensitive lineage commitment of neural stem cells

Adult neural stem cells (NSCs) play important roles in learning and memory and are negatively impacted by neurological disease. It is known that biochemical and genetic factors regulate self-renewal and differentiation, and it has recently been suggested that mechanical and solid-state cues, such as extracellular matrix (ECM) stiffness, can also regulate the functions of NSCs and other stem cell types. However, relatively little is known of the molecular mechanisms through which stem cells transduce mechanical inputs into fate decisions, the extent to which mechanical inputs instruct fate decisions versus select for or against lineage-committed blast populations, or the in vivo relevance of mechanotransductive signaling molecules in native stem cell niches. Here we demonstrate that ECM-derived mechanical signals act through Rho GTPases to activate the cellular contractility machinery in a key early window during differentiation to regulate NSC lineage commitment. Furthermore, culturing NSCs on increasingly stiff ECMs enhances RhoA and Cdc42 activation, increases NSC stiffness, and suppresses neurogenesis. Likewise, inhibiting RhoA and Cdc42 or downstream regulators of cellular contractility rescues NSCs from stiff matrix- and Rho GTPase-induced neurosuppression. Importantly, Rho GTPase expression and ECM stiffness do not alter proliferation or apoptosis rates indicating that an instructive rather than selective mechanism modulates lineage distributions. Finally, in the adult brain, RhoA activation in hippocampal progenitors suppresses neurogenesis, analogous to its effect in vitro. These results establish Rho GTPase-based mechanotransduction and cellular stiffness as biophysical regulators of NSC fate in vitro and RhoA as an important regulatory protein in the hippocampal stem cell niche.

High-throughput indentational elasticity measurements of hydrogel extracellular matrix substrates

Much interest surrounds the effect of extracellular matrix (ECM) elasticity on cell behavior. Here we present a rapid method for measuring the elasticity of synthetic ECM substrates based on indentation of the substrate with a ferromagnetic sphere and optical tracking of the resulting deformation. We find that this method yields order-of-magnitude agreement with atomic force microscopy elasticity measurements, but that the degree of this agreement depends strongly on sphere density and gel elasticity. In its regime of greatest accuracy, we envision that this method may be used for high-throughput characterization of ECM substrates in cell biological studies.

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.

Optimization approaches for the design of additively manufactured scaffolds

Scaffolds play a pivotal role in tissue engineering, promoting the synthesis of neo extra-cellular matrix (ECM), and providing temporary mechanical support for the cells during tissue regeneration. Advances introduced by additive manufacturing techniques have significantly improved the ability to regulate scaffold architecture, enhancing the control over scaffold shape and porosity. Thus, considerable research efforts have been devoted to the fabrication of 3D porous scaffolds with optimized micro-architectural features. This chapter gives an overview of the methods for the design of additively manufactured scaffolds and their applicability in tissue engineering (TE). Along with a survey of the state of the art, the Authors will also present a recently developed method, called Load-Adaptive Scaffold Architecturing (LASA), which returns scaffold architectures optimized for given applied mechanical loads systems, once the specific stress distribution is evaluated through Finite Element Analysis (FEA).

The feeding practices and structure questionnaire : construction and initial validation in a sample of Australian first-time mothers and their 2-year olds

Background Early feeding practices lay the foundation for children’s eating habits and weight gain. Questionnaires are available to assess parental feeding but overlapping and inconsistent items, subscales and terminology limit conceptual clarity and between study comparisons. Our aim was to consolidate a range of existing items into a parsimonious and conceptually robust questionnaire for assessing feeding practices with very young children (<3 years). Methods Data were from 462 mothers and children (age 21–27 months) from the NOURISH trial. Items from five questionnaires and two study-specific items were submitted to a priori item selection, allocation and verification, before theoretically-derived factors were tested using Confirmatory Factor Analysis. Construct validity of the new factors was examined by correlating these with child eating behaviours and weight. Results Following expert review 10 factors were specified. Of these, 9 factors (40 items) showed acceptable model fit and internal reliability (Cronbach’s α: 0.61-0.89). Four factors reflected non-responsive feeding practices: ‘Distrust in Appetite’, ‘Reward for Behaviour’, ‘Reward for Eating’, and ‘Persuasive Feeding’. Five factors reflected structure of the meal environment and limits: ‘Structured Meal Setting’, ‘Structured Meal Timing’, ‘Family Meal Setting’, ‘Overt Restriction’ and ‘Covert Restriction’. Feeding practices generally showed the expected pattern of associations with child eating behaviours but none with weight. Conclusion The Feeding Practices and Structure Questionnaire (FPSQ) provides a new reliable and valid measure of parental feeding practices, specifically maternal responsiveness to children’s hunger/satiety signals facilitated by routine and structure in feeding. Further validation in more diverse samples is required.

A vibrational spectroscopic study of the phosphate mineral rimkorolgite (Mg,Mn2+)5(Ba, Sr)(PO4)4·8H2O from Kovdor massif, Kola Peninsula, Russia

We have studied aspect of the molecular structure of the phosphate mineral rimkorolgite from Zheleznyi iron mine, Kovdor massif, Kola Peninsula, Russia, using SEM with EDX and vibrational spectroscopy. Qualitative chemical analysis shows a homogeneous phase, composed by P, Mg, Ba, Mn and Ca. Small amounts of Si were also observed. An intense Raman peak at 975 cm−1 is assigned to the PO43− ν1 symmetric stretching mode. The Raman band at 964 cm−1 is attributed to the HPO42− ν1 symmetric stretching vibration. Raman bands observed at 1016, 1035, 1052, 1073, 1105 and 1135 cm−1 are attributed to the ν3 antisymmetric stretching vibrations of the HPO42− and PO43− units. Complexity in the spectra of the phosphate bending region is observed. The broad Raman band at 3272 cm−1 is assigned to the water stretching vibration. Vibrational spectroscopy enables aspects on the molecular structure of rimkorolgite to be undertaken.

Discrete phase-locked loop systems and spreadsheets

This paper demonstrates the use of a spreadsheet in exploring non-linear difference equations that describe digital control systems used in radio engineering, communication and computer architecture. These systems, being the focus of intensive studies of mathematicians and engineers over the last 40 years, may exhibit extremely complicated behaviour interpreted in contemporary terms as transition from global asymptotic stability to chaos through period-doubling bifurcations. The authors argue that embedding advanced mathematical ideas in the technological tool enables one to introduce fundamentals of discrete control systems in tertiary curricula without learners having to deal with complex machinery that rigorous mathematical methods of investigation require. In particular, in the appropriately designed spreadsheet environment, one can effectively visualize a qualitative difference in the behviour of systems with different types of non-linear characteristic.

Highly NO2 sensitive caesium doped graphene oxide conductometric sensors

Here we report on the synthesis of caesium doped graphene oxide (GO-Cs) and its application to the development of a novel NO2 gas sensor. The GO, synthesized by oxidation of graphite through chemical treatment, was doped with Cs by thermal solid-state reaction. The samples, dispersed in DI water by sonication, have been drop-casted on standard interdigitated Pt electrodes. The response of both pristine and Cs doped GO to NO2 at room temperature is studied by varying the gas concentration. The developed GO-Cs sensor shows a higher response to NO2 than the pristine GO based sensor due to the oxygen functional groups. The detection limit measured with GO-Cs sensor is ≈90 ppb.

Robust multiple-sensing-modality data fusion using Gaussian Process Implicit Surfaces

The ability to build high-fidelity 3D representations of the environment from sensor data is critical for autonomous robots. Multi-sensor data fusion allows for more complete and accurate representations. Furthermore, using distinct sensing modalities (i.e. sensors using a different physical process and/or operating at different electromagnetic frequencies) usually leads to more reliable perception, especially in challenging environments, as modalities may complement each other. However, they may react differently to certain materials or environmental conditions, leading to catastrophic fusion. In this paper, we propose a new method to reliably fuse data from multiple sensing modalities, including in situations where they detect different targets. We first compute distinct continuous surface representations for each sensing modality, with uncertainty, using Gaussian Process Implicit Surfaces (GPIS). Second, we perform a local consistency test between these representations, to separate consistent data (i.e. data corresponding to the detection of the same target by the sensors) from inconsistent data. The consistent data can then be fused together, using another GPIS process, and the rest of the data can be combined as appropriate. The approach is first validated using synthetic data. We then demonstrate its benefit using a mobile robot, equipped with a laser scanner and a radar, which operates in an outdoor environment in the presence of large clouds of airborne dust and smoke.

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Do good things and talk about them : a theory of academics usage of enterprise social networks for impression management tactics

Enterprise social networks provide benefits especially for knowledge-intensive work as they enable communication, collaboration and knowledge exchange. These platforms should therefore lead to increased adoption and use by knowledge-intensive workers such as consultants or indeed researchers. Our interest is in ascertaining whether scientific researchers use enterprise social networks as part of their work practices. This focus is motivated by an apparent schism between a need for researchers to exchange knowledge and profile themselves, and the aversion to sharing breakthrough ideas and joining in an ever-increasing publishing and marketing game. We draw on research on academic work practices and impression management to develop a model of academics’ ESN usage for impression management tactics. We describe important constructs of our model, offer strategies for their operationalization and give an outlook to our ongoing empirical study of the use of an ESN platform by 20 schools across six faculties at an Australian university.

Towards a theory of individual-level discontinuance of information systems use

I develop a model of individuals’ intentions to discontinue information system use. Understanding these intentions is important because they give insights into users’ willingness to carry out system tasks, and provide a basis for maintenance decisions as well as possible replacement decisions. I offer a first conceptualization of factors determining users’ discontinuance intentions on basis of existing literature on technology use, status quo bias and dual factor concepts. The model is grounded in rational choice theory to distinguish determinants of a conscious decision between continuing or discontinuing IS use. I provide details on the empirical test of the model through a field study of IS users in a retail organization. The work will have implications for theory on information systems continuance and dual-factor logic in information system use. The empirical findings will provide suggestions for managers dealing with cessation of information systems and work routine changes in organizations.