Nonlinear electrophoresis of dielectric and metal spheres in a nematic liquid crystal

Electrophoresis is a motion of charged dispersed particles relative to a fluid in a uniform electric field. The effect is widely used to separate macromolecules, to assemble colloidal structures, to transport particles in nano- and micro-fluidic devices and displays. Typically, the fluid is isotropic (for example, water) and the electrophoretic velocity is linearly proportional to the electric field. In linear electrophoresis, only a direct current (DC) field can drive the particles. An alternate current (AC) field is more desirable because it allows one to overcome problems such as electrolysis and absence of steady flows. Here we show that when the electrophoresis is performed in a nematic fluid, the effect becomes strongly non-linear with a velocity component that is quadratic in the applied voltage and has a direction that generally differs from the direction of linear velocity. The new phenomenon is caused by distortions of the LC orientation around the particle that break the fore-aft (or left-right) symmetry. The effect allows one to transport both charged and neutral particles, even when the particles themselves are perfectly symmetric (spherical), thus enabling new approaches in display technologies, colloidal assembly, separation, microfluidic and micromotor applications.Comment: 15 pages, 4 figure

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Usefulness of event-related potentials in the assessment of mild cognitive impairment

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine if changes in latencies and amplitudes of the major waves of Auditory Event-Related Potentials (AERP), correlate with memory status of patients with mild cognitive impairment (MCI) and conversion to Alzheimer's disease (AD).</p> <p>91 patients with MCI (mean ± SD age = 66.6 ± 5.4, MMSE score = 27.7) and 30 age-matched healthy control (AMHC) subjects (mean ± SD age = 68.9 ± 9.9) were studied. 54 patients were re-examined after an average period of 14(± 5.2) months. During this time period 5 patients converted to AD. Between-group differences in latency and amplitude of the major AERP waves (N200, P300 and Slow Wave) were determined. Within each group, correlation coefficients (CC) between these characteristics of the different AERP waves were calculated. Finally, for patients, CCs were determined among each AERP wave and their age and MMSE scores. Confirmatory factor analysis (CFA) was used to examine the underlying structure of waveforms both in the control and the patient groups.</p> <p>Results</p> <p>Latencies of all major AERP components were prolonged in patients compared to controls. Patients presented with significantly higher N200 amplitudes, but no significant differences were observed in P300 amplitudes. Significant differences between follow-up and baseline measurements were found for P300 latency (p = 0.009), N200 amplitude (p < 0.001) and P300 amplitude (p = 0.05). MMSE scores of patients did not correlate with latency or amplitude of the AERP components. Moreover, the establishment of a N200 latency cut-off value of 287 ms resulted in a sensitivity of 100% and a specificity of 91% in the prediction of MCI patients that converted to AD.</p> <p>Conclusion</p> <p>Although we were not able to establish significant correlations between latencies and amplitudes of N200, P300 and SW and the patients' performance in MMSE, which is a psychometric test for classifying patients suffering from MCI, our results point out that the disorganization of the AERP waveform in MCI patients is a potential basis upon which a neurophysiologic methodology for identifying and "staging" MCI can be sought. We also found that delayed N200 latency not only identifies memory changes better than the MMSE, but also may be a potential predictor of the MCI patients who convert to AD.</p

Proteolytic Processing of Nlrp1b Is Required for Inflammasome Activity

Nlrp1b is a NOD-like receptor that detects the catalytic activity of anthrax lethal toxin and subsequently co-oligomerizes into a pro-caspase-1 activation platform known as an inflammasome. Nlrp1b has two domains that promote oligomerization: a NACHT domain, which is a member of the AAA+ ATPase family, and a poorly characterized Function to Find Domain (FIIND). Here we demonstrate that proteolytic processing within the FIIND generates N-terminal and C-terminal cleavage products of Nlrp1b that remain associated in both the auto-inhibited state and in the activated state after cells have been treated with lethal toxin. Functional significance of cleavage was suggested by the finding that mutations that block processing of Nlrp1b also prevent the ability of Nlrp1b to activate pro-caspase-1. By using an uncleaved mutant of Nlrp1b, we established the importance of cleavage by inserting a heterologous TEV protease site into the FIIND and demonstrating that TEV protease processed this site and induced inflammasome activity. Proteolysis of Nlrp1b was shown to be required for the assembly of a functional inflammasome: a mutation within the FIIND that abolished cleavage had no effect on self-association of a FIIND-CARD fragment, but did reduce the recruitment of pro-caspase-1. Our work indicates that a post-translational modification enables Nlrp1b to function

Angiotensin II Activates the Calcineurin/NFAT Signaling Pathway and Induces Cyclooxygenase-2 Expression in Rat Endometrial Stromal Cells

Cyclooxygenase (COX)-2, the inducible isoform of cyclooxygenase, plays a role in the process of uterine decidualization and blastocyst attachment. On the other hand, overexpression of COX-2 is involved in the proliferation of the endometrial tissue during endometriosis. Deregulation of the renin-angiotensin-system plays a role in the pathophysiology of endometriosis and pre-eclampsia. Angiotensin II increases intracellular Ca2+ concentration by targeting phospholypase C-gamma in endometrial stromal cells (ESC). A key element of the cellular response to Ca2+ signals is the activity of the Ca2+- and calmodulin-dependent phosphatase calcineurin. Our first aim was to study whether angiotensin II stimulated Cox-2 gene expression in rat ESC and to analyze whether calcineurin activity was involved. In cells isolated from non-pregnant uteri, COX-2 expression -both mRNA and protein- was induced by co-stimulation with phorbol ester and calcium ionophore (PIo), as well as by angiotensin II. Pretreatment with the calcineurin inhibitor cyclosporin A inhibited this induction. We further analyzed the role of the calcineurin/NFAT signaling pathway in the induction of Cox-2 gene expression in non-pregnant rat ESC. Cyclosporin A abolished NFATc1 dephosphorylation and translocation to the nucleus. Cyclosporin A also inhibited the transcriptional activity driven by the Cox-2 promoter. Exogenous expression of the peptide VIVIT -specific inhibitor of calcineurin/NFAT binding- blocked the activation of Cox-2 promoter and the up-regulation of COX-2 protein in these cells. Finally we analyzed Cox-2 gene expression in ESC of early-pregnant rats. COX-2 expression -both mRNA and protein- was induced by stimulation with PIo as well as by angiotensin II. This induction appears to be calcineurin independent, since it was not abrogated by cyclosporin A. In conclusion, angiotensin II induced Cox-2 gene expression by activating the calcineurin/NFAT signaling pathway in endometrial stromal cells of non-pregnant but not of early-pregnant rats. These results might be related to differential roles that COX-2 plays in the endometrium

Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ2 = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs

Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ2 = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs