1,331 research outputs found
Using Available Volume to Predict Fluid Diffusivity in Random Media
We propose a simple equation for predicting self-diffusivity of fluids
embedded in random matrices of identical, but dynamically frozen, particles
(i.e., quenched-annealed systems). The only nontrivial input is the volume
available to mobile particles, which also can be predicted for two common
matrix types that reflect equilibrium and non-equilibrium fluid structures. The
proposed equation can account for the large differences in mobility exhibited
by quenched-annealed systems with indistinguishable static pair correlations,
illustrating the key role that available volume plays in transport.Comment: to appear in Physical Review E (12 pages, 4 figures
Cyfip1 Haploinsufficiency Does Not Alter GABAA Receptor δ-Subunit Expression and Tonic Inhibition in Dentate Gyrus PV+ Interneurons and Granule Cells
Copy number variation (CNV) at chromosomal region 15q11.2 is linked to increased risk of neurodevelopmental disorders including autism and schizophrenia. A significant gene at this locus is cytoplasmic fragile X mental retardation protein (FMRP) interacting protein 1 (CYFIP1). CYFIP1 protein interacts with FMRP, whose monogenic absence causes fragile X syndrome (FXS). Fmrp knock-out has been shown to reduce tonic GABAergic inhibition by interacting with the δ-subunit of the GABAA receptor (GABAAR). Using in situ hybridization (ISH), qPCR, Western blotting techniques, and patch clamp electrophysiology in brain slices from a Cyfip1 haploinsufficient mouse, we examined δ-subunit mediated tonic inhibition in the dentate gyrus (DG). In wild-type (WT) mice, DG granule cells (DGGCs) responded to the δ-subunit-selective agonist THIP with significantly increased tonic currents. In heterozygous mice, no significant difference was observed in THIP-evoked currents in DGGCs. Phasic GABAergic inhibition in DGGC was also unaltered with no difference in properties of spontaneous IPSCs (sIPSCs). Additionally, we demonstrate that DG granule cell layer (GCL) parvalbumin-positive interneurons (PV+-INs) have functional δ-subunit-mediated tonic GABAergic currents which, unlike DGGC, are also modulated by the α1-selective drug zolpidem. Similar to DGGC, both IPSCs and THIP-evoked currents in PV+-INs were not different between Cyfip1 heterozygous and WT mice. Supporting our electrophysiological data, we found no significant change in hippocampal δ-subunit mRNA expression or protein level and no change in α1/α4-subunit mRNA expression. Thus, Cyfip1 haploinsufficiency, mimicking human 15q11.2 microdeletion syndrome, does not alter hippocampal phasic or tonic GABAergic inhibition, substantially differing from the Fmrp knock-out mouse model
Generalized Rosenfeld scalings for tracer diffusivities in not-so-simple fluids: Mixtures and soft particles
Rosenfeld [Phys. Rev. A 15, 2545 (1977)] noticed that casting transport
coefficients of simple monatomic, equilibrium fluids in specific dimensionless
forms makes them approximately single-valued functions of excess entropy. This
has predictive value because, while the transport coefficients of dense fluids
are difficult to estimate from first principles, excess entropy can often be
accurately predicted from liquid-state theory. Here, we use molecular
simulations to investigate whether Rosenfeld's observation is a special case of
a more general scaling law relating mobility of particles in mixtures to excess
entropy. Specifically, we study tracer diffusivities, static structure, and
thermodynamic properties of a variety of one- and two-component model fluid
systems with either additive or non-additive interactions of the hard-sphere or
Gaussian-core form. The results of the simulations demonstrate that the effects
of mixture concentration and composition, particle-size asymmetry and
additivity, and strength of the interparticle interactions in these fluids are
consistent with an empirical scaling law relating the excess entropy to a new
dimensionless (generalized Rosenfeld) form of tracer diffusivity, which we
introduce here. The dimensionless form of the tracer diffusivity follows from
knowledge of the intermolecular potential and the transport / thermodynamic
behavior of fluids in the dilute limit. The generalized Rosenfeld scaling
requires less information, and provides more accurate predictions, than either
Enskog theory or scalings based on the pair-correlation contribution to the
excess entropy. As we show, however, it also suffers from some limitations,
especially for systems that exhibit significant decoupling of individual
component tracer diffusivities.Comment: 15 pages, 10 figure
Quantitative Imaging of B1 Cyclin Expression Across the Cell Cycle Using Green Fluorescent Protein Tagging and Epifluorescence
In this article, we report the number of cyclin B1 proteins tagged with enhanced green fluorescent protein (eGFP) in fixed U‐2 OS cells across the cell cycle. We use a quantitative analysis of epifluorescence to determine the number of eGFP molecules in a nondestructive way, and integrated over the cell we find 104 to 105 molecules. Based on the measured number of eGFP tagged cyclin B1 proteins, knowledge of cyclin B1 dynamics through the cell cycle, and the cell morphology, we identify the stages of cells in the cell cycle
By design : negotiating flexible learning in the built environment discipline
The term ‘flexible education’ is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning ‘matching’ tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher’s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world
Understanding the Basis for Down Syndrome Phenotypes
Down syndrome is a collection of features that are caused by trisomy for human Chromosome 21. While elevated transcript levels of the more than 350 genes on the chromosome are primarily responsible, it is likely that multiple genetic mechanisms underlie the numerous ways in which development and function diverge in individuals with trisomy 21 compared to euploid individuals. We consider genotype–phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy
A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.
Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments
The effect of motion adaptation on the position of elements in the visual saltation illusion.
The visual saltation illusionVillusory motion induced by presenting elements first to one peripheral location, then to another, in rapid and regular successionVbelongs to a class of stimuli for which a difference exists between the physical and perceived positions of elements. Rather than being perceived at their physical location, elements are perceived as traveling smoothly across the area between the two locations. In separate experiments, we examined the distortion to the saltatory path caused by adaptation to an upward drifting grating presented between the two physically stimulated locations (where elements were nonetheless perceived), and at the first location of physical stimulation. Where adaptation occurred between the two sites of physical stimulation, the saltatory path was distorted as if elements had a physical origin at that location; elements perceived as arising from the central location were subject to a motion aftereffect (MAE). Where motion adaptation overlapped the first site of physical stimulation, the saltatory path was affected only for those elements perceived as arising from the first location; elements perceived at the central location (but physically presented at the first site of stimulation) were not subject to an MAE. Our results indicate that the impact of motion adaptation on position is dependent on the perceived, and not the physical, location of elements
Ultrasensitivity of the Bacillus subtilis sporulation decision
Starving Bacillus subtilis cells execute a gene expression program
resulting in the formation of stress-resistant spores. Sporulation
master regulator, Spo0A, is activated by a phosphorelay and controls
the expression of a multitude of genes, including the forespore-
specific sigma factor σF and the mother cell-specific sigma
factor σE. Identification of the system-level mechanism of the sporulation
decision is hindered by a lack of direct control over Spo0A
activity. This limitation can be overcome by using a synthetic system
in which Spo0A activation is controlled by inducing expression
of phosphorelay kinase KinA. This induction results in a switch-like
increase in the number of sporulating cells at a threshold of KinA.
Using a combination of mathematical modeling and single-cell microscopy,
we investigate the origin and physiological significance
of this ultrasensitive threshold. The results indicate that the phosphorelay
is unable to achieve a sufficiently fast and ultrasensitive
response via its positive feedback architecture, suggesting that the
sporulation decision is made downstream. In contrast, activation
of σF in the forespore and of σE in the mother cell compartments
occurs via a cascade of coherent feed-forward loops, and thereby
can produce fast and ultrasensitive responses as a result of KinA
induction. Unlike σF activation, σE activation in the mother cell
compartment only occurs above the KinA threshold, resulting in
completion of sporulation. Thus, ultrasensitive σE activation explains
the KinA threshold for sporulation induction. We therefore infer
that under uncertain conditions, cells initiate sporulation but postpone
making the sporulation decision to average stochastic fluctuations
and to achieve a robust population response
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