Electrostatic interactions between rough dielectric particles.

From colloid suspension to particle aggregation in protoplanetary formation, electrostatic attraction and repulsion between particles is a key mechanism behind the aggregation and clustering of particles. Although most studies have focused on canonical spherical particles, it remains unclear how nonspherical and rough dielectric particles interact and whether the complicated interplay between roughness and charge distribution affects their force couplings. Here a boundary-element method model was leveraged to study electrostatic interactions between charged dielectric particles with modular, axisymmetric surface features. Charge accumulation at convex surface asperities decreases the strength of electrostatic interactions between particles, and the sensitivity of the electrostatic force to the particle surface roughness and orientation is especially apparent at small particle separations. Surface interactions between the particle near-contact regions were isolated to determine the degree that near-contact interactions dictate the relationship between the net electrostatic force and the particle roughness and orientation. A correction factor ΔF is introduced to recover higher order dielectric effects from a low order analytical model. Finally, implications of surface charge asymmetries produced for different particle orientations and surface roughnesses on the long-standing problem of triboelectrification are discussed.

Effect of electrostatic interaction on impact breakage of agglomerates formed by charged dielectric particles.

In this paper, the prototypical process of the normal impact of dense agglomerates is investigated using the discrete element method-boundary element method coupled simulations. The agglomerate consists of 50 charged particles with the surface energy equal to 10mJ/m^{2}. The particles are assumed to be tribocharged and follow an exponential charge distribution, while the varying levels of coupled polarization are also considered. Simulation results reveal that the presence of the electrostatic interactions due to particle charging and polarization could drive more pronounced re-agglomeration after the collision, which effectively reduces the degree of agglomerate fragmentation. Moreover, when quantifying the collision outcomes using the fragmentation ratio, the influence of the electrostatic force is most significant at a moderate incident velocity. This is because, at such incident velocities, the impact is violent enough to break the agglomerate, but many ejected fragments are usually at low velocities and are attracted back by the long-range electrostatic force. Furthermore, the electrostatic force between same-sign particles even becomes attractive when particles are strongly polarized, leading to qualitative changes in particle dynamics. Finally, by comparing the collision outcomes under different incident velocities, the contact interactions are found to prevail when particles are still bounded in the agglomerate, while the electrostatic interaction becomes dominant after particles detach from each other.

Effect of interparticle dipolar interaction on pore clogging during microfiltration.

We present numerical investigations on the clogging of adhesive particles carrying electric dipoles at pore scale using an adhesive discrete element method (DEM). Based on the simulation results, the long-range dipolar interaction is reported to promote the clogging process, which is quantified by the bulk permeability, the penetrating particle number, and the particle capture efficiency. A clogging phase diagram is constructed in terms of the Stokes number (St) and the adhesion parameter (Ad) for both neutral and polarized particles. The influence of the dipolar interaction on the clogging-nonclogging transition is then described by the shifted boundary on the diagram. Also, the cake structure is characterized by different mathematical descriptions. A looser structure is formed with the increase of both the short-range adhesion and the long-range dipolar interaction. More ordered structures, such as particle chains, are observed in the presence of the stronger dipolar interaction. Furthermore, fluid stress is found to be essential in the compression and restructuring of the cake structure. Finally, a schematic representation of the cake structure is established, which provides a general physical picture showing the relationship between the cake structure and the particle-scale interactions.

Clock-dependent and independent transcriptional control of the two isoforms from the mouse Rorgamma gene.

Accumulating evidence indicate that molecular mechanisms generating circadian rhythms display some degree of tissue-specificity. More specifically, distinct patterns of expression for nuclear receptors of the ROR family indicate that the transcriptional control of the clock gene Bmal1 differs among tissues. This study aims to investigate the expression of Rorgammaisoforms (Rorgamma and Rorgammat) and characterize the molecular mechanisms underlying their tissue-specific expression. The expression of Rorgamma isoforms was assessed in mouse liver, muscle, thymus and testis throughout 24 h using quantitative RT-PCR. Although the expression of Rorgamma was rhythmic in the liver and thymus, it was constitutively expressed in muscle and testis. In contrast, the expression of Rorgammat was constitutive in all four tissues. Furthermore, rhythmic expression of Rorgamma was impaired in Clock mutant mice whereas the mutation had no effect on Rorgammat expression. In line with these findings, luciferase assays revealed that transcription of the Rorgamma promoter is clock-controlled whereas that of Rorgammat promoter is essentially clock-independent. Our results provide insights into the molecular mechanisms that lead to differential expression of Rorgamma and Rorgammat and are suggestive of a framework that might account for tissue-specific circadian regulation.

Insight into the PTEN - p85α interaction and lipid binding properties of the p85α BH domain.

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in regulating cell growth and cell survival and is frequently deregulated in cancer cells. p85α regulates the p110α lipid kinase, and also stabilizes and stimulates PTEN, the lipid phosphatase that downregulates this pathway. In this report, we determined that the p85α BH domain binds several phosphorylated phosphoinositide lipids, an interaction that could help localize p85α to membranes rich in these lipids. We also identified key residues responsible for mediating PTEN - p85α complex formation. Based on these experimental results, a docking model for the PTEN - p85α BH domain complex was developed that is consistent with the known binding interactions for both PTEN and p85α. This model involves extensive side-chain and peptide backbone contacts between both the PASE and C2 domains of PTEN with the p85α BH domains. The p85α BH domain residues shown to be important for PTEN binding were p85α residues E212, Q221, K225, R228 and H234. We also verified experimentally the importance of PTEN-E91 in mediating the interaction with the p85α BH domain. These results shed new light on the mechanism of PTEN regulation by p85α.

Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation.

The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85α mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85α mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85α towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85α BH domain mutants (E137K, E217K, R262T E297K) for bovine p85α BH and found that the mutations did not alter the overall domain structure. Thus, several p85α mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85α BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activity.

Coordinated diurnal regulation of genes from the Dlk1-Dio3 imprinted domain: implications for regulation of clusters of non-paralogous genes.

The functioning of the genome is tightly related to its architecture. Therefore, understanding the relationship between different regulatory mechanisms and the organization of chromosomal domains is essential for understanding genome regulation. The majority of imprinted genes are assembled into clusters, share common regulatory elements, and, hence, represent an attractive model for studies of regulation of clusters of non-paralogous genes. Here, we investigated the relationship between genomic imprinting and diurnal regulation of genes from the imprinted domain of mouse chromosome 12. We compared gene expression patterns in C57BL/6 mice and congenic mice that carry the imprinted region from a Mus musculus molossinus strain MOLF/Ei. In the C57BL/6 mice, a putative enhancer/oscillator regulated the expression of only Mico1/Mico1os, whereas in the congenic mice its influence was spread onto Rtl1as, Dio3 and Dio3os, i.e. the distal part of the imprinted domain, resulting in coordinated diurnal variation in expression of five genes. Using additional congenic strains we determined that in C57BL/6 the effect of the putative enhancer/oscillator was attenuated by a linked dominant trans-acting factor located in the distal portion of chromosome 12. Our data demonstrate that (i) in adult organs, mRNA levels of several imprinted genes vary during the day, (ii) genetic variation may remove constraints on the influence of an enhancer and lead to spreading of its effect onto neighboring genes, thereby generating genotype-dependent expression patterns and (iii) different regulatory mechanisms within the same domain act independently and do not seem to interfere with each other.

Novel imprinted transcripts from the Dlk1-Gtl2 intergenic region, Mico1 and Mico1os, show circadian oscillations.

Most of the known imprinted genes are assembled into clusters that share common imprinting control regions (ICRs). Non-coding transcripts are often associated with ICRs and implicated in imprinting regulation. We undertook a systematic search for transcripts originating from the Dlk1-Gtl2 intergenic region that contains the ICR for the chromosome 12 imprinted cluster and identified two overlapping transcripts expressed from opposite strands exclusively from the maternal chromosome. These novel imprinted transcripts most likely represent non-coding RNAs and are located telomeric to the IG DMR, extending the proximal boundary of the region of maternal-specific transcription. Their expression is tissue-specific and shows diurnal and circadian oscillations.Therefore, we named these novel transcripts maternal intergenic circadian oscillating 1 (Mico1) and Mico1, opposite strand (Mico1os).