A Role for Amyloid in Cell Aggregation and Biofilm Formation

Cell adhesion molecules in Saccharomyces cerevisiae and Candida albicans contain amyloid-forming sequences that are highly conserved. We have now used site-specific mutagenesis and specific peptide perturbants to explore amyloid-dependent activity in the Candida albicans adhesin Als5p. A V326N substitution in the amyloid-forming region conserved secondary structure and ligand binding, but abrogated formation of amyloid fibrils in soluble Als5p and reduced cell surface thioflavin T fluorescence. When displayed on the cell surface, Als5p with this substitution prevented formation of adhesion nanodomains and formation of large cellular aggregates and model biofilms. In addition, amyloid nanodomains were regulated by exogenous peptides. An amyloid-forming homologous peptide rescued aggregation and biofilm activity of Als5pV326N cells, and V326N substitution peptide inhibited aggregation and biofilm activity in Als5pWT cells. Therefore, specific site mutation, inhibition by anti-amyloid peturbants, and sequence-specificity of pro-amyloid and anti-amyloid peptides showed that amyloid formation is essential for nanodomain formation and activation

Student Characteristics as Predictors of Teachers’ Implementation of a Kindergarten Readiness Program

Recent years have seen increasing numbers of classroom-based interventions designed to enhance the school readiness of at-risk preschoolers. Even the most comprehensive, well-designed programs can suffer from limited effectiveness due to low-frequency implementation by teachers. The current study presents findings from the Building Bridges project (BB), an integrated program targeting school readiness in Head Start and low-income child care centers. Previous studies have reported the role of teacher-level and program-level characteristics in predicting teacher implementation of an intervention. The present study examines the role of student characteristics—language and math ability, social skills, and behavioral functioning—in predicting implementation exposure. These associations were examined in the context of program type (Head Start, child care) and intervention condition (consultation, no consultation). 88 classrooms (41 Head Start, 47 child care) participated in the BB intervention. Implementation exposure was predicted by several distinct student characteristics. Teachers whose students exhibited poorer language skills implemented significantly more BB activities, a finding that was consistent across program types and intervention conditions. A marginally significant trend was identified for oppositional behavior when interacted with intervention group in that teachers whose students demonstrated higher rates of oppositional behavior implemented fewer intervention activities when they did not have a consultant. Teachers in child care centers with a BB consultant had higher rates of implementation than did teachers in all other groups. These findings provide important information regarding the student-level characteristics that should be evaluated in order to optimize implementation of an intervention

Collapse to Black Holes in Brans-Dicke Theory: II. Comparison with General Relativity

We discuss a number of long-standing theoretical questions about collapse to black holes in the Brans-Dicke theory of gravitation. Using a new numerical code, we show that Oppenheimer-Snyder collapse in this theory produces black holes that are identical to those of general relativity in final equilibrium, but are quite different from those of general relativity during dynamical evolution. We find that there are epochs during which the apparent horizon of such a black hole passes {\it outside\/} the event horizon, and that the surface area of the event horizon {\it decreases\/} with time. This behavior is possible because theorems which prove otherwise assume $R_{ab}l^al^b \ge 0$ for all null vectors $l^a$. We show that dynamical spacetimes in Brans-Dicke theory can violate this inequality, even in vacuum, for any value of $\omega$.Comment: 24 pages including figures, uuencoded gz-compressed postscript, Submitted to Phys Rev

Predicting teacher participation in a classroom-based, integrated preventive intervention for preschoolers

Preschools provide a promising setting in which to conduct preventive interventions for childhood problems, but classroom programs can only be effective if teachers are willing and able to implement them. This study is one of the first to investigate predictors of the frequency of teacher participation in a classroom-based, randomized controlled trial of an integrated prevention program for preschoolers. The intervention was designed to promote school readiness with an integrated social and academic program, to be implemented by teachers with the support of classroom consultants. The current study is part of a larger project conducted with Head Start and community child care centers that serve primarily economically disadvantaged families; 49 teachers from 30 centers participated in this study. Overall, teachers conducted approximately 70% of the program activities. Participation decreased significantly over time from the first to the final week of the intervention, and also decreased within each week of the intervention, from the first to the final weekly activity. Teachers working at community child care centers implemented more intervention activities than did Head Start teachers. Teacher concerns about the intervention, assessed prior to training, predicted less participation. In addition, teachers' participation was positively related to their perception that their centers and directors were supportive, collegial, efficient, and fair, as well as their job satisfaction and commitment. Teacher experience, education, ethnicity, and self-efficacy were not significantly related to participation. In multi-level models that considered center as a level of analysis, substantial variance was accounted for by centers, pointing to the importance of considering center-level predictors in future research

Business ethics : practical proposals

While most people agree that the inculcation of ethical awareness is desirable, the means of stimulating this awareness vary among companies, industries and cultures. The fundamental question surrounding the difference between social responsibility and ethics is addressed. Guidelines for establishing ethical priorities from both the individual, group and organisational perspectives are provided. <br /

Two-Particle-Self-Consistent Approach for the Hubbard Model

Even at weak to intermediate coupling, the Hubbard model poses a formidable challenge. In two dimensions in particular, standard methods such as the Random Phase Approximation are no longer valid since they predict a finite temperature antiferromagnetic phase transition prohibited by the Mermin-Wagner theorem. The Two-Particle-Self-Consistent (TPSC) approach satisfies that theorem as well as particle conservation, the Pauli principle, the local moment and local charge sum rules. The self-energy formula does not assume a Migdal theorem. There is consistency between one- and two-particle quantities. Internal accuracy checks allow one to test the limits of validity of TPSC. Here I present a pedagogical review of TPSC along with a short summary of existing results and two case studies: a) the opening of a pseudogap in two dimensions when the correlation length is larger than the thermal de Broglie wavelength, and b) the conditions for the appearance of d-wave superconductivity in the two-dimensional Hubbard model.Comment: Chapter in "Theoretical methods for Strongly Correlated Systems", Edited by A. Avella and F. Mancini, Springer Verlag, (2011) 55 pages. Misprint in Eq.(23) corrected (thanks D. Bergeron

The impact of neogene grassland expansion and aridification on the isotopic composition of continental precipitation

The late Cenozoic was a time of global cooling, increased aridity, and expansion of grasslands. In the last two decades numerous records of oxygen isotopes have been collected to assess plant ecological changes, understand terrestrial paleoclimate, and to determine the surface history of mountain belts. The δ¹⁸(O) values of these records, in general, increase from the mid-Miocene to the Recent. We suggest that these records record an increase in aridity and expansion of grasslands in midlatitude continental regions. We use a nondimensional isotopic vapor transport model coupled with a soil water isotope model to evaluate the role of vapor recycling and transpiration by different plant functional types. This analysis shows that increased vapor recycling associated with grassland expansion along with biomechanistic changes in transpiration by grasses themselves conspires to lower the horizontal gradient in the δ¹⁸(O) of atmospheric vapor as an air mass moves into continental interiors. The resulting signal at a given inland site is an increase in δ¹⁸(O) of precipitation with the expansion of grasslands and increasing aridity, matching the general observed trend in terrestrial Cenozoic δ¹⁸(O) records. There are limits to the isotopic effect that are induced by vapor recycling, which we refer to here as a “hydrostat.” In the modern climate, this hydrostatic limit occurs at approximately the boundary between forest and grassland ecosystems

Inelastic Black Hole Scattering from Charged Scalar Amplitudes

We explain how the lowest-order classical gravitational radiation produced during the inelastic scattering of two Schwarzschild black holes in General Relativity can be obtained from a tree scattering amplitude in gauge theory coupled to scalar fields. The gauge calculation is related to gravity through the double copy. We remove unwanted scalar forces which can occur in the double copy by introducing a massless scalar in the gauge theory, which is treated as a ghost in the link to gravity. We hope these methods are a step towards a direct application of the double copy at higher orders in classical perturbation theory, with the potential to greatly streamline gravity calculations for phenomenological applications.Comment: 28 pages, 6 figure

Ligand Mobility Modulates Immunological Synapse Formation and T Cell Activation

T cell receptor (TCR) engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in formation of the immunological synapse (IS), a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC) formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses

Rapid Reversal of Chondroitin Sulfate Proteoglycan Associated Staining in Subcompartments of Mouse Neostriatum during the Emergence of Behaviour

BACKGROUND: The neostriatum, the mouse homologue of the primate caudate/putamen, is the input nucleus for the basal ganglia, receiving both cortical and dopaminergic input to each of its sub-compartments, the striosomes and matrix. The coordinated activation of corticostriatal pathways is considered vital for motor and cognitive abilities, yet the mechanisms which underlie the generation of these circuits are unknown. The early and specific targeting of striatal subcompartments by both corticostriatal and nigrostriatal terminals suggests activity-independent mechanisms, such as axon guidance cues, may play a role in this process. Candidates include the chondroitin sulfate proteoglycan (CSPG) family of glycoproteins which have roles not only in axon guidance, but also in the maturation and stability of neural circuits where they are expressed in lattice-like perineuronal nets (PNNs). METHODOLOGY/PRINCIPAL FINDINGS: The expression of CSPG-associated structures and PNNs with respect to neostriatal subcompartments has been examined qualitatively and quantitatively using double-labelling for Wisteria floribunda agglutinin (WFA), and the mu-opioid receptor (muOR), a marker for striosomes, at six postnatal ages in mice. We find that at the earliest ages (postnatal day (P)4 and P10), WFA-positive clusters overlap preferentially with the striosome compartment. By P14, these clusters disappear. In contrast, PNNs were first seen at P10 and continued to increase in density and spread throughout the caudate/putamen with maturation. Remarkably, the PNNs overlap almost exclusively with the neostriatal matrix. CONCLUSIONS/SIGNIFICANCE: This is the first description of a reversal in the distribution of CSPG associated structures, as well as the emergence and maintenance of PNNs in specific subcompartments of the neostriatum. These results suggest diverse roles for CSPGs in the formation of functional corticostriatal and nigrostriatal connectivity within the striosome and matrix compartments of the developing caudate/putamen