Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis, but the mechanisms of transduction are poorly understood. Previous work showed that the conversion of integrins to a high-affinity state mediates a subset of shear responses, including cell alignment and gene expression. Here we investigate the pathway upstream of integrin activation. PECAM-1 (which directly transmits mechanical force), vascular endothelial cell cadherin (which functions as an adaptor) and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) comprise a mechanosensory complex. Together, these receptors are sufficient to confer responsiveness to flow in heterologous cells. In support of the relevance of this pathway in vivo, PECAM-1-knockout mice do not activate NF-kappaB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.

We present a systematic study of the effect of size and shape on the spectral response of individual silver nanoparticles. An experimental method has been developed that begins with the detection and characterization of isolated nanoparticles in the optical far field. The plasmon resonance optical spectrum of many individual nanoparticles are then correlated to their size and shape using high-resolution transmission electron microscopy. We find that specific geometrical shapes give distinct spectral responses. In addition, inducing subtle changes in the particles’ morphology by heating causes a shift in the individual particle spectrum and provides a simple means of tuning the spectral response to a desired optical wavelength. Improved colloidal preparation methods could potentially lead to homogeneous populations of identical particle shapes and colors. These multicolor colloids could be used as biological labels, surface enhanced Raman scattering substrates, or near field optical microscopy sources covering the full range of wavelengths in the visible spectrum.

We introduce and demonstrate the use of colloidal silver plasmonresonant particles (PRPs) as optical reporters in typical biological assays. PRPs are ultrabright, nanosized optical scatterers, which scatter light elastically and can be prepared with a scattering peak at any color in the visible spectrum. PRPs are readily observed individually with a microscope configured for dark-field microscopy, with white-light illumination of typical power. Here we illustrate the use of PRPs, surface coated with standard ligands, as target-specific labels in an in situ hybridization and an immunocytology assay. We propose that PRPs can replace or complement established labels, such as those based on radioactivity, fluorescence, chemiluminescence, or enzymatic͞colorimetric detection that are used routinely in biochemistry, cell biology, and medical diagnostic applications. Moreover, because PRP labels are nonbleaching and bright enough to be rapidly identified and counted, an ultrasensitive assay format based on single-target molecule detection is now practical. We also present the results of a model sandwich immunoassay for goat anti-biotin antibody, in which the number of PRP labels counted in an image constitutes the measured signal. R obust optical reporters for diagnostic detection and͞or labeling are used extensively in areas of biomedical and clinical chemistry research, for instance in immunology, microbiology, molecular biology, pharmacology, pathology, virology, or drug testing. Current methods of detection use colorimetric, fluorometric, or chemiluminescent (1) reporter molecules either as enzyme substrates or as direct labels. The measured optical signal in such assays typically results from the accumulated sum of all reporter labels present in the target region, including contributions from both specific and nonspecific binding events. Alternative optical assay formats based on detecting and counting individual binding events are possible, but have not yet been demonstrated to be feasible. Although single fluorescent molecules, upconverting phosphors (2), and the recently introduced quantum dots (3, 4) can be individually detected, such systems have very low light yield and often exhibit time-dependent blinking and irreversible photodestruction. Thus, to indicate reliably the presence of a target, a population of such labels is still required, potentially limiting both the minimum quantity of target detected and the spatial localization of the labeled region.We introduce here a new assay platform (both probe and instrumentation) capable of individual target molecule detection that uses plasmon-resonant particles (PRPs) as optical reporters. PRPs are metallic nanoparticles, typically 40-100 nm in diameter, which scatter light elastically with remarkable efficiency because of a collective resonance of the conduction electrons in the metal (i.e., the surface plasmon resonance; ref. 5). The magnitude, peak wavelength, and spectral bandwidth of the plasmon resonance associated with a nanoparticle are dependent on the ...

Following leads from differential emotions theory and empirical research, we evaluated an index of emotion knowledge as a long-term predictor of positive and negative social behavior and academic competence in a sample of children from economically disadvantaged families (N = 72). The index of emotion knowledge represents the child's ability to recognize and label emotion expressions. We administered control and predictor measures when the children were 5 years old and obtained criterion data at age 9. After controlling for verbal ability and temperament, our index of emotion knowledge predicted aggregate indices of positive and negative social behavior and academic competence. Path analysis showed that emotion knowledge mediated the effect of verbal ability on academic competence. We argue that the ability to detect and label emotion cues facilitates positive social interactions and that a deficit in this ability contributes to behavioral and learning problems. Our findings have implications for primary prevention.

Knots are being discovered with increasing frequency in both biological and synthetic macromolecules and have been fundamental topological targets for chemical synthesis for the past two decades. Here, we report on the synthesis of the most complex non-DNA molecular knot prepared to date: the self-assembly of five bis-aldehyde and five bis-amine building blocks about five metal cations and one chloride anion to form a 160-atom-loop molecular pentafoil knot (five crossing points). The structure and topology of the knot is established by NMR spectroscopy, mass spectrometry and X-ray crystallography, revealing a symmetrical closed-loop double helicate with the chloride anion held at the centre of the pentafoil knot by ten CH ... Cl -hydrogen bonds. The one-pot self-assembly reaction features an exceptional number of different design elements-some well precedented and others less well known within the context of directing the formation of (supra)molecular species. We anticipate that the strategies and tactics used here can be applied to the rational synthesis of other higher-order interlocked molecular architectures.K nots are important structural features in DNA 1 , are found in some proteins [2][3][4][5] and are thought to play a significant role in the physical properties of both natural and synthetic polymers 6,7 . Although billions of prime knots are known to mathematics 8 , to date the only ones to have succumbed to chemical synthesis using building blocks other than DNA are the topologically trivial unknot (that is, a simple closed loop without any crossing points) and the next simplest knot (featuring three crossing points), the trefoil knot 9,10 . A pentafoil knot-also known as a cinquefoil knot or Solomon's seal knot (the 5 1 knot in Alexander-Briggs notation 11 )-is a torus knot 12 with five crossing points, is inherently chiral, and is the fourth prime knot (following the unknot, trefoil knot and figure-of-eight knot) in terms of number of crossing points and complexity 8,11,12 .Sauvage reported the first molecular knot synthesis 13 , using a linear metal helicate 14 to generate the three crossing points required for a trefoil knot. Although other syntheses of trefoil knots have been reported [15][16][17][18][19][20][21][22] (as have composites of trefoil knots 23 and other molecular topologies such as catenanes [24][25][26][27][28] and Borromean links 29 ), higher-order molecular knots remain elusive. Here, we report on the synthesis of a molecular pentafoil knot that combines the use of metal helicates to create crossover points 30 , anion template assembly to form a cyclic array of the correct size [31][32][33] , and the joining of the metal complexes by reversible imine bond formation 34-37 aided by the gauche effect 38 to make the continuous 160-atom-long covalent backbone of the most complex non-DNA molecular knot prepared to date.So far, attempts to make molecular knots with more than three crossing points by extending the linear helicate strategy of Sauvage to ligands with more coordination sites...

In irons bound: Linear diamine and formylpyridine subcomponents form a tetrahedral cage with iron(II) in water (see scheme). This cage traps hydrophobic guests with high specificity within a rigid cavity, isolating them from the aqueous environment. The cage may be broken, releasing the guest, upon the addition of a triamine. It may also be unlocked by adding acid, allowing the guest to be reversibly released until base is added, relocking it within.

We examined the relations between emotionality, emotion processing, and aggression in 182 first-and second-grade children. Consistent with Tomkins' and Izard's theoretical predictions, emotionality correlated with emotion processing. In particular, the happiness component of emotionality correlated with emotion attribution accuracy and empathy, the anger component correlated with anger attribution bias and empathy, and the fear component correlated with fear attribution bias. Multiple emotion processing deficits-including emotion attribution accuracy, anger attribution bias, and self-report of empathy-placed children at risk for heightened levels of teacher-reported aggression. Mediational analyses revealed that an emotion processing risk index fit a model of significant partial mediation between happiness and aggression but not between anger and aggression. The results suggest the multifaceted manner in which children's emotion experiences may influence the development of aggressive tendencies.

We examined the relations of verbal ability and self-regulation in preschool to emotion knowledge in first grade, and concurrent relations between emotion knowledge and indexes of social functioning in 143 children from low-income families. After controlling for children's verbal ability in preschool, teacher reports of attentional control and caregiver reports of behavioral control in preschool predicted children's emotion expression knowledge and emotion situation knowledge 2 years later. After controlling for verbal ability and attentional and behavioral control, children's emotion knowledge predicted concurrent teacher-reported social problems and social withdrawal. Results suggest that low levels of emotion knowledge co-occur with many important aspects of children's early social adaptation.