Significant Depolarization Research Articles

17-β estradiol promotes autophagy and induces cellular senescence in breast cancer cells.

e12523 Background: The fact that estrogen (17-β estradiol or E2) is a known carcinogen notwithstanding, mounting evidence suggest that E2 has the potential to exert anti-cancer effects against various forms of cancer. Using in vitro models we, and others, have previously demonstrated that E2 disrupts intracellular iron metabolism in such a way that arrests cell cycling in breast and ovarian cancer cells. However, the cellular and molecular correlates underlying this cytostatic effect of E2 in cancer cells remain elusive. Methods: In this study, metastatic (MDA-MB-231) and non-metastatic (MCF-7) breast cancer cells treated with 20 nM E2 were assessed for mitochondrial function, cell proliferation, apoptosis and senescence at different time points post treatment. Results: E2 treatment resulted in a significant mitochondrial membrane depolarization; an outcome that associated with a significant loss of mitochondrial function and the accumulation of auto-phagosomes. It also significantly upregulated the expression of the cell cycle regulating cyclin-dependent kinase inhibitor, p21 protein and enhanced the activation (de-phosphorylation) of the tumour suppressor retinoblastoma (Rb) protein. Although, as previously shown, E2 did not induced classis apoptosis; it resulted in a significant elevation in senescence-associated β- galactosidase levels. Conclusions: In summary, these findings suggest that E2 treatment mediates its anti-cancer potential by disrupting mitochondrial function and precipitating autophagy and cell senescence.

Simulation of the depolarization ratio of adiabatic water clouds by lidar

We have simulated the depolarization signal in adiabatic water clouds due to the occurrence of multiple scattering when measuring the microphysics characteristics using depolarization lidar. The number density of the adiabatic water clouds is constant in the vertical direction. The liquid water content and the effective radius increase nonlinearly with the height, and the varying rule is controlled by the barometric pressure, temperature, and the thermodynamic formulas. The wavelength of the lidar is chosen as 0.355 µm. From the computed results, we can see that the depolarization ratio of the adiabatic clouds increases with the penetration depth of the clouds, and increases with the increase in the receiving field of view angle (FOV). There are great differences between the adiabatic water clouds and the homogeneous clouds in the varying rules of the depolarization ratio. The effective radius of the clouds with a higher cloud base height is less than that of the clouds with a lower cloud base, and the depolarization ratio is also small with the same number density and observation conditions.

The Main Metabolites of Fluorouracil + Adriamycin + Cyclophosphamide (FAC) Are Not Major Contributors to FAC Toxicity in H9c2 Cardiac Differentiated Cells.

In the clinical practice, the combination of 5-fluorouracil (5-FU) + Adriamycin (also known as doxorubicin, DOX) + cyclophosphamide (CYA) (known as FAC) is used to treat breast cancer. The FAC therapy, however, carries some serious risks, namely potential cardiotoxic effects, although the mechanisms are still unclear. In the present study, the role of the main metabolites regarding FAC-induced cardiotoxicity was assessed at clinical relevant concentrations. Seven-day differentiated H9c2 cells were exposed for 48 h to the main metabolites of FAC, namely the metabolite of 5-FU, α-fluoro-β-alanine (FBAL, 50 or 100 μM), of DOX, doxorubicinol (DOXOL, 0.2 or 1 μM), and of CYA, acrolein (ACRO, 1 or 10 μM), as well as to their combination. The parent drugs (5-FU 50 μM, DOX 1 μM, and CYA 50 μM) were also tested isolated or in combination with the metabolites. Putative cytotoxicity was evaluated through phase contrast microscopy, Hoechst staining, membrane mitochondrial potential, and by two cytotoxicity assays: the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and the neutral red (NR) lysosomal incorporation. The metabolite DOXOL was more toxic than FBAL and ACRO in the MTT and NR assays. When in combination, neither FBAL nor ACRO increased DOXOL-induced cytotoxicity. No nuclear condensation was observed for any of the tested combinations; however, a significant mitochondrial potential depolarization after FBAL 100 μM + DOXOL 1 μM + ACRO 10 μM or FBAL 100 μM + DOXOL 1 μM exposure was seen at 48 h. When tested alone DOX 1 μM was more cytotoxic than all the parent drugs and metabolites in both the cytotoxicity assays performed. These results demonstrated that DOXOL was the most toxic of all the metabolites tested; nonetheless, the metabolites do not seem to be the major contributors to FAC-induced cardiotoxicity in this cardiac model.

Input-to-Output Instantaneous Polarization Characterization

This paper proposes a method to represent and predict received signal instantaneous polarization states as a function of arbitrary transmit polarization states for time-dispersive channels. The model incorporates frequency-dependent characterizations to represent the polarization dispersion behavior of a received signal across its bandwidth in a multipath channel. The representation takes advantage of signal dispersion features typical of depolarized signals, and employs subbanded characterizations to achieve polarization representations exhibiting high degrees of polarization in each subband. Experiments are conducted that demonstrate the utility of the modeling approach to predict polarization dispersion responses for arbitrary transmit polarizations based on measurements from two orthogonal transmit polarizations.

Icariin Protects Bone Marrow Mesenchymal Stem Cells Against Iron Overload Induced Dysfunction Through Mitochondrial Fusion and Fission, PI3K/AKT/mTOR and MAPK Pathways.

Iron overload has been reported to contribute to bone marrow mesenchymal stem cells (BMSCs) damage, but the precise mechanism still remains elusive. Icariin, a major bioactive monomer belonging to flavonoid glucosides isolated from Herba Epimedii, has been shown to protect cells from oxidative stress induced apoptosis. The aim of this study was to investigate whether icariin protected against iron overload induced dysfunction of BMSCs and its underlying mechanism. In this study, we found that iron overload induced by 100 μM ferric ammonium citrate (FAC) caused apoptosis of BMSCs, promoted cleaved caspase-3 and BAX protein expressions while inhibited Bcl-2 protein expression, which effects were significantly attenuated by icariin treatment. In addition, iron overload induced significant depolarization of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and inhibition of mitochondrial fusion/fission, which effects were also attenuated by icariin treatment. Meanwhile, we found that iron overload induced by 100 μM FAC significantly inhibited mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, inhibited DRP1 and Cytochrome C protein translocation from the cytoplasm to mitochondria. Icariin at concentration of 1 μM was able to promote mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, and increase DRP1 and cytochrome C protein translocation from the cytoplasm to mitochondria. Further, osteogenic differentiation and proliferation of BMSCs was significantly inhibited by iron overload, but icariin treatment rescued both osteogenic differentiation and proliferation of BMSCs. Further studies showed that icariin attenuated iron overload induced inactivation of the PI3K/AKT/mTOR pathway and activation of the ERK1/2 and JNK pathways. In summary, our study indicated that icariin was able to protect against iron overload induced dysfunction of BMSCs. These effects were potentially related to the modulation of mitochondrial fusion and fission, activation of the PI3K/AKT/mTOR pathway and inhibition of ERK1/2 and JNK pathways.

Novel linear lipopeptide paenipeptin C\u2032 binds to lipopolysaccharides and lipoteichoic acid and exerts bactericidal activity by the disruption of cytoplasmic membrane

BackgroundThere is an urgent need to develop potent antimicrobials for the treatment of infections caused by antibiotic-resistant bacterial pathogens. Paenipeptin C′ (C8-Pat) is a novel linear lipopeptide recently discovered by our group. The objectives of this study were to determine the time-kill kinetics of paenipeptin C′ against Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213 and to investigate its mechanism of action.ResultsPaenipeptin C′ was synthesized by solid-phase peptide synthesis and purified by HPLC to homogeneity. Paenipeptin C′ showed concentration-dependent bactericidal activity against P. aeruginosa and S. aureus. Purified lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria and lipoteichoic acid (LTA) from Gram-positive bacteria significantly decreased the antibacterial activity of paenipeptin C′, which indicated that LPS and LTA on cell surfaces are likely the initial binding targets of this antibiotic agent. Moreover, paenipeptin C′ damaged bacterial cytoplasmic membranes, as evidenced by the depolarization of membrane potential and leakage of intracellular potassium ions. Specifically, paenipeptin C′ at 32–64 μg/mL caused a significant membrane potential depolarization in P. aeruginosa and S. aureus. This antibiotic at 64–128 μg/mL rapidly induced the release of intracellular potassium ions from P. aeruginosa and S. aureus. Transmission electron microscopy imaging results showed that paenipeptin C′ at bactericidal concentrations perturbed the cell envelopes, leading to the loss of intracellular contents.ConclusionsTherefore, paenipeptin C' exerts its bactericidal effect through damaging bacterial cytoplasmic membrane.

β3 -adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn2+ and reactive nitrogen species.

Role of β3 -AR dysregulation, as either cardio-conserving or cardio-disrupting mediator, remains unknown yet. Therefore, we examined the molecular mechanism of β3 -AR activation in depressed myocardial contractility using a specific agonist CL316243 or using β3 -AR overexpressed cardiomyocytes. Since it has been previously shown a possible correlation between increased cellular free Zn2+ ([Zn2+ ]i ) and depressed cardiac contractility, we first demonstrated a relation between β3 -AR activation and increased [Zn2+ ]i , parallel to the significant depolarization in mitochondrial membrane potential in rat ventricular cardiomyocytes. Furthermore, the increased [Zn2+ ]i induced a significant increase in messenger RNA (mRNA) level of β3 -AR in cardiomyocytes. Either β3 -AR activation or its overexpression could increase cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels, in line with significant changes in nitric oxide (NO)-pathway, including increases in the ratios of pNOS3/NOS3 and pGSK-3β/GSK-3β, and PKG expression level in cardiomyocytes. Although β3 -AR activation induced depression in both Na+ - and Ca2+ -currents, the prolonged action potential (AP) seems to be associated with a marked depression in K+ -currents. The β3 -AR activation caused a negative inotropic effect on the mechanical activity of the heart, through affecting the cellular Ca2+ -handling, including its effect on Ca2+ -leakage from sarcoplasmic reticulum (SR). Our cellular level data with β3 -AR agonism were supported with the data on high [Zn2+ ]i and β3 -AR protein-level in metabolic syndrome (MetS)-rat heart. Overall, our present data can emphasize the important deleterious effect of β3 -AR activation in cardiac remodeling under pathological condition, at least, through a cross-link between β3 -AR activation, NO-signaling, and [Zn2+ ]i pathways. Moreover, it is interesting to note that the recovery in ER-stress markers with β3 -AR agonism in hyperglycemic cardiomyocytes is favored. Therefore, how long and to which level the β3 -AR agonism would be friend or become foe remains to be mystery, yet.

Is There a Polarization Horizon?

Modern radio spectrometers make measurement of polarized intensity as a function of Faraday depth possible. I investigate the effect of depolarization along a model line of sight. I model sightlines with two components informed by observations: a warm ionized medium with a lognormal electron density distribution and a narrow, denser component simulating a spiral arm or Hii region, all with synchrotron-emitting gas mixed in. I then calculate the polarized intensity from 300–1800 MHz and calculate the resulting Faraday depth spectrum. The idealized synthetic observations show far more Faraday complexity than is observed in Global Magneto-Ionic Medium Survey observations. In a model with a very nearby Hii region observed at low frequencies, most of the effects of a “depolarization wall” are evident: the Hii region depolarizes background emission, and less (but not zero) information from beyond the Hii region reaches the observer. In other cases, the effects are not so clear, as significant amounts of information reach the observer even through significant depolarization, and it is not clear that low-frequency observations sample largely different volumes of the interstellar medium than high-frequency observations. The observed Faraday depth can be randomized such that it does not always have any correlation with the true Faraday depth.

The susceptibility of cochlear outer hair cells to cyclodextrin is not related to their electromotile activity

Niemann-Pick Type C1 (NPC1) disease is a fatal neurovisceral disorder caused by dysfunction of NPC1 protein, which plays a role in intracellular cholesterol trafficking. The cholesterol-chelating agent, 2-hydroxypropyl-β-cyclodextrin (HPβCD), is currently undergoing clinical trials for treatment of this disease. Though promising in alleviating neurological symptoms, HPβCD causes irreversible hearing loss in NPC1 patients and outer hair cell (OHC) death in animal models. We recently found that HPβCD-induced OHC death can be significantly alleviated in a mouse model lacking prestin, an OHC-specific motor protein required for the high sensitivity and sharp frequency selectivity of mammalian hearing. Since cholesterol status is known to influence prestin’s electromotility, we examined how prestin contributes to HPβCD-induced OHC death in the disease context using the NPC1 knockout (KO) mouse model (NPC1-KO). We found normal expression and localization of prestin in NPC1-KO OHCs. Whole-cell patch-clamp recordings revealed a significant depolarization of the voltage-operating point of prestin in NPC1-KO mice, suggesting reduced levels of cholesterol in the lateral membrane of OHCs that lack NPC1. OHC loss and elevated thresholds were found for high frequency regions in NPC1-KO mice, whose OHCs retained their sensitivity to HPβCD. To investigate whether prestin’s electromotile function contributes to HPβCD-induced OHC death, the prestin inhibitor salicylate was co-administered with HPβCD to WT and NPC1-KO mice. Neither oral nor intraperitoneal administration of salicylate mitigated HPβCD-induced OHC loss. To further determine the contribution of prestin’s electromotile function, a mouse model expressing a virtually nonelectromotile prestin protein (499-prestin) was subjected to HPβCD treatment. 499-prestin knockin mice showed no resistance to HPβCD-induced OHC loss. As 499-prestin maintains its ability to bind cholesterol, our data imply that HPβCD-induced OHC death is ascribed to the structural role of prestin in maintaining the OHC’s lateral membrane, rather than its motor function.

All-Fiber Passive Alignment-Free Depolarizers Capable of Depolarizing Narrow Linewidth Signals

We report on two fully-fiberized, input polarization independent depolarizer configurations that do not need any alignment once fabricated. This makes them suitable for real-world applications. The first configuration uses polarization-maintaining (PM) fibers and relatively few components. The second configuration uses standard (non-PM) single mode fibers to introduce the large time delays needed to enable narrow-linewidth signal depolarization, albeit at the cost of a slightly increased component count and insertion loss. We theoretically analyze the depolarization performance of the proposed configurations as a function of various depolarizer parameters. Subsequently, we design the depolarizers considering the imperfections of standard commercially available components. Finally, we fabricate prototypes of both configurations, characterize their depolarization performance using sources of variable linewidth, and compare the experimental results with theoretical analysis. The fabricated depolarizers are shown to be capable of the depolarization of 20 MHz and 1 MHz linewidth signals with residual degree of polarization below 4%.

Nrf2 Signaling in Sodium Azide-Treated Oligodendrocytes Restores Mitochondrial Functions.

Mitochondrial dysfunctions mark a critical step in many central nervous system (CNS) pathologies, including multiple sclerosis (MS). Such dysfunctions lead to depolarization of mitochondrial membranes and imbalanced redox homeostasis. In this context, reactive oxygen species (ROS) are potentially deleterious but can also act as an important signaling step for cellular maintenance. The transcription factor nuclearfactor (erythroid-derived2)-like 2 (Nrf2), the key regulator in the cellular oxidative stress-response, induces a battery of genes involved in repair and regeneration. Here, we investigated the relevance of Nrf2 signaling for the prevention of cellular damage caused by dysfunctional mitochondria. We employed sodium azide (SA) as mitochondrial inhibitor on oligodendroglial OliNeu cells in vitro, and the cuprizone model with wild type and GFAP-Cre+::Keap1loxP/loxP mice to induce mitochondrial defects. The importance of Nrf2 for cellular functions and survival after SA treatment was elucidated by in vitro knockdown experiments with shRNA directed against Nrf2 and its inhibitor Keap1 as well as by methysticin treatment. Metabolic activity, cytotoxicity, and depolarization of the mitochondrial membrane were analyzed after SA treatment. The expression of Nrf2 target genes as well as endoplasmic reticulum stress response genes was additionally measured by real-time PCR (in vitro) and PCR gene arrays (in vivo). Treatment of OliNeu cells with SA resulted in significant depolarization of the mitochondrial membrane, decreased metabolic activity, and increased cytotoxicity. This was partly counteracted in Nrf2-hyperactivated cells and intensified in Nrf2-knockdown cells. Our studies demonstrate a keyrole of Nrf2 in maintaining cellular functions and survival in the context of mitochondrial dysfunction.

Novel Glycopolymer Eradicates Antibiotic- and CCCP-Induced Persister Cells in Pseudomonas aeruginosa.

Antibiotic treatments often fail to completely eradicate a bacterial infection, leaving behind an antibiotic-tolerant subpopulation of intact bacterial cells called persisters. Persisters are considered a major cause for treatment failure and are thought to greatly contribute to the recalcitrance of chronic infections. Pseudomonas aeruginosa infections are commonly associated with elevated levels of drug-tolerant persister cells, posing a serious threat to human health. This study represents the first time a novel large molecule polycationic glycopolymer, poly (acetyl, arginyl) glucosamine (PAAG), has been evaluated against antibiotic and carbonyl cyanide m-chlorophenylhydrazone induced P. aeruginosa persisters. PAAG eliminated eliminated persisters at concentrations that show no significant cytotoxicity on human lung epithelial cells. PAAG demonstrated rapid bactericidal activity against both forms of induced P. aeruginosa persister cells resulting in complete eradication of the in vitro persister cells within 24 h of treatment. PAAG demonstrated greater efficacy against persisters in vitro than antibiotics currently being used to treat persistent chronic infections such as tobramycin, colistin, azithromycin, aztreonam, and clarithromycin. PAAG caused rapid permeabilization of the cell membrane and caused significant membrane depolarization in persister cells. PAAG efficacy against these bacterial subpopulations suggests it may have substantial therapeutic potential for eliminating recurrent P. aeruginosa infections.

The role of autophagy induction in the mechanism of cytoprotective effect of resveratrol

We aimed at studying the potential mechanisms in the preventive effect of resveratrol on serum deprivation induced caspase 3 activation on non-transformed cells. MethodsApoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation, reactive oxygen species production and depolarization of the mitochondrial membrane were measured by fluorescence methods. The involvement of intracellular receptors and autophagy in the effect of resveratrol were analyzed by using specific agonists and antagonists. The role of autophagy was further examined by Western Blot analysis of its protein markers, LC3-II and p62 as well as by acridine orange staining of acidic vacuoles. ResultsWe found that neither aromatic hydrocarbon receptors nor estrogen receptors play an important role in the cytoprotective effect of resveratrol. Reactive oxygen species production was not significantly altered by either serum deprivation or resveratrol treatment. In the presence of serum deprivation resveratrol however, induced a significant depolarization in mitochondrial membrane potential. The autophagy inhibitor, chloroquine not only eliminated the preventive effect of resveratrol, but also turned it to deleterious suggesting the prominent role of autophagy induction in the cytoprotective effect. Resveratrol did not alter LC3-II expression, but facilitated p62 degradation in serum deprived cells, suggesting its ability to augment the late phase of autophagy and thus promote the autophagic flux. ConclusionWe have demonstrated that resveratrol can protect primary fibroblasts against serum deprivation induced apoptosis by provoking mild mitochondrial stress and consequent up-regulation of autophagic flux.

Imaging the three-dimensional orientation and rotational mobility of fluorescent emitters using the Tri-spot point spread function

Fluorescence photons emitted by single molecules contain rich information regarding their rotational motions, but adapting single-molecule localization microscopy (SMLM) to measure their orientations and rotational mobilities with high precision remains a challenge. Inspired by dipole radiation patterns, we design and implement a Tri-spot point spread function (PSF) that simultaneously measures the three-dimensional orientation and the rotational mobility of dipole-like emitters across a large field of view. We show that the orientation measurements done using the Tri-spot PSF are sufficiently accurate to correct the anisotropy-based localization bias, from 30 nm to 7 nm, in SMLM. We further characterize the emission anisotropy of fluorescent beads, revealing that both 20-nm and 100-nm diameter beads emit light significantly differently from isotropic point sources. Exciting 100-nm beads with linearly polarized light, we observe significant depolarization of the emitted fluorescence using the Tri-spot PSF that is difficult to detect using other methods. Finally, we demonstrate that the Tri-spot PSF detects rotational dynamics of single molecules within a polymer thin film that are not observable by conventional SMLM.

Multi-Acting Mitochondria-Targeted Platinum(IV) Prodrugs of Kiteplatin with α-Lipoic Acid in the Axial Positions.

Platinum(II) drugs are activated intracellularly by aquation of the leaving groups and then bind to DNA, forming DNA adducts capable to activate various signal-transduction pathways. Mostly explored in recent years are Pt(IV) complexes which allow the presence of two additional ligands in the axial positions suitable for the attachment of other cancer-targeting ligands. Here we have extended this strategy by coordinating in the axial positions of kiteplatin ([PtCl2(cis-1,4-DACH)], DACH = Diaminocyclohexane) and its CBDCA (1,1-cyclobutanedicarboxylate) analogue the antioxidant α-Lipoic acid (ALA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK). The new compounds (cis,trans,cis-[Pt(CBDCA)(ALA)2(cis-1,4-DACH)], 2, and cis,trans,cis-[PtCl2(ALA)2(cis-1,4-DACH)], 3), after intracellular reduction, release the precursor Pt(II) species and two molecules of ALA. The Pt residue is able to target DNA, while ALA could act on mitochondria as activator of the pyruvate dehydrogenase complex, thus suppressing anaerobic glycolysis. Compounds 2 and 3 were tested in vitro on a panel of five human cancer cell lines and compared to cisplatin, oxaliplatin, and kiteplatin. They proved to be much more effective than the reference compounds, with complex 3 most effective in 3D spheroid tumor cultures. Notably, treatment of human A431 carcinoma cells with 2 and 3 did not determine increase of cellular ROS (usually correlated to inhibition of mitochondrial PDK) and did not induce a significant depolarization of the mitochondrial membrane or alteration of other morphological mitochondrial parameters.

Thymol inhibits oral squamous cell carcinoma growth via mitochondria-mediated apoptosis.

Thymol is a transient receptor potential ankyrin subtype 1 channel, (TRPA1) agonist found in thyme and oregano. Thymol has antioxidant, anti-inflammatory, and antimicrobial properties; thus, thymol is added to many commercially available products including Listerine mouthwash. Thymol is also cytotoxic to HL-60 (acute promyelocytic leukemia) cells in vitro. Therefore, we evaluated the effects of thymol against oral squamous cell carcinoma (OSCC) and its anticancer mechanism-of-action. The antiproliferative effects of thymol in OSCC Cal27 cells were determined by MTS assays. Antitumor effects were evaluated in Cal27- and HeLa-derived mouse xenografts. Calcium imaging, mitochondrial transmembrane potential (ΔΨm) studies, and Western blot analysis of cleaved PARP (c-PARP) evaluated thymol's mechanism-of-action. Thymol had significant, long-lasting antiproliferative effects in vitro. In vivo, thymol displayed significant antitumor effects in Cal27-derived tumors. Thymol's anticancer effects were confirmed in HeLa-derived xenografts demonstrating that thymol effects are not tumor-type specific. Calcium imaging verified calcium influx in Cal27 cells that were reversed with the TRPA1 antagonist, HC030031. However, no calcium influx was seen in HeLa cells indicating that TRP channels do not regulate thymol cytotoxicity. This was confirmed using cell viability assays in which pre-treatment with HC030031 had no effect on thymol cytotoxicity. Instead, ΔΨm studies revealed that thymol induces significant ΔΨm depolarization and apoptosis. Our findings provide the first evidence of thymol's novel antitumor effects against OSCC in vivo, which do not rely on TRPA1 activity. Instead, we show that thymol induces mitochondrial dysfunction and apoptosis and may be efficacious against multiple cancers.

Carbamazepine-induced suppression of repetitive firing in CA1 pyramidal neurons is greater in the dorsal hippocampus than the ventral hippocampus

Medial temporal lobe epilepsy (mTLE)–the most common form of focal epilepsy–is defined by recurrent partial seizures originating within the medial temporal lobe. Such seizures are commonly associated with the anterior hippocampus (as opposed to the posterior hippocampus), and refractory to the currently available anti-epileptic drugs (AED) for about one third of patients. Unfortunately, the mechanisms driving seizure generation and AED efficacy along the longitudinal hippocampal axis remain poorly understood. Recently, several groups investigating differences in excitability along the rodent longitudinal hippocampal axis have demonstrated that CA1 pyramidal neurons from the rodent ventral hippocampus (the rodent homolog of the human anterior hippocampus) are intrinsically more excitable than their dorsal counterparts (the rodent homolog of the human posterior hippocampus). This phenotypic difference is accompanied by significant differences in gene expression along the longitudinal hippocampal axis, which include gene products–such as voltage-gated sodium channel β-subunits–known to influence AED efficacy. Given this phenotypic heterogeneity, and the differential expression of gene products known to influence anti-epileptic drug efficacy, we sought to investigate the efficacy of the classical use-dependent sodium channel blocker, carbamazepine, in CA1 pyramidal neurons across the longitudinal hippocampal axis. Accordingly, we performed whole-cell current-clamp recordings on CA1 pyramidal neurons from acute hippocampal slices prepared from the dorsal and ventral hippocampus, and found that acute exposure to 100 μM carbamazepine induced a significantly greater suppression of repetitive firing for dorsal neurons relative to ventral neurons by inducing profound spike frequency adaptation (SFA). Moreover, we observed a small, but significant depolarization of resting membrane potential (RMP) for dorsal neurons (but not ventral neurons), following exposure to carbamazepine. Together, these observations demonstrate that carbamazepine’s effect is concentrated in the dorsal hippocampus, which could provide meaningful insight into the side effect profile of carbamazepine (and related anti-epileptic drugs) in non-epileptic tissue, and inform future work investigating the mechanisms of carbamazepine resistance in epileptic tissue.

Polarized point sources in the LOFAR Two-meter Sky Survey: A preliminary catalog

The polarization properties of radio sources at very low frequencies (<200 MHz) have not been widely measured, but the new generation of low-frequency radio telescopes, including the Low Frequency Array (LOFAR: a Square Kilometre Array Low pathfinder), now gives us the opportunity to investigate these properties. In this paper, we report on the preliminary development of a data reduction pipeline to carry out polarization processing and Faraday tomography for data from the LOFAR Two-meter Sky Survey (LOTSS) and present the results of this pipeline from the LOTSS preliminary data release region (10h45m–15h30m right ascension, 45°–57° declination, 570 square degrees). We have produced a catalog of 92 polarized radio sources at 150 MHz at 4.′3 resolution and 1 mJy rms sensitivity, which is the largest catalog of polarized sources at such low frequencies. We estimate a lower limit to the polarized source surface density at 150 MHz, with our resolution and sensitivity, of 1 source per 6.2 square degrees. We find that our Faraday depth measurements are in agreement with previous measurements and have significantly smaller errors. Most of our sources show significant depolarization compared to 1.4 GHz, but there is a small population of sources with low depolarization indicating that their polarized emission is highly localized in Faraday depth. We predict that an extension of this work to the full LOTSS data would detect at least 3400 polarized sources using the same methods, and probably considerably more with improved data processing.

Cadmium zinc telluride as a mid-infrared variable retarder

The electro-optic behavior of cadmium zinc telluride is examined in the mid-infrared region between 3 and 11 μm, for applied DC field strengths of up to 106 V/m. The measurements performed here include full characterization of the polarization state of the transmitted light by means of the Stokes vector. We demonstrate the suitability of this material for DC variable retarder applications such as those achieved by quarter- or half-wave retardation. A comparison of two different metallic coatings for electrodes, gold and indium, reveals important differences in performance that are attributed to the homogeneity of the field through the bulk of the crystal. We illustrate that, in the case of both metals, the same electro-optic coefficients are measured, but regions of higher and lower retardation result in significant depolarization in the case of gold. Such depolarization may adversely affect the contrast ratio in a light valve, or increase the voltage necessary for the operation of an arbitrary polarization state generator.

Repeatability Assessment of Intravascular Polarimetry in Patients.

Intravascular polarimetry with polarization sensitive optical frequency domain imaging (PS-OFDI) measures polarization properties of the vessel wall and offers characterization of coronary atherosclerotic lesions beyond the cross-sectional image of arterial microstructure available to conventional OFDI. A previous study of intravascular polarimetry in cadaveric human coronary arteries found that tissue birefringence and depolarization provide valuable insight into key features of atherosclerotic plaques. In addition to various tissue components, catheter and sample motion can also influence the polarization of near infrared light as used by PS-OFDI. This paper aimed to evaluate the robustness and repeatability of imaging tissue birefringence and depolarization in a clinical setting. 30 patients scheduled for percutaneous coronary intervention at the Erasmus Medical Center underwent repeated PS-OFDI pullback imaging, using commercial imaging catheters in combination with a custom-built PS-OFDI console. We identified 274 matching cross sections among the repeat pullbacks to evaluate the reproducibility of the conventional backscatter intensity, the birefringence, and the depolarization signals at each spatial location across the vessel wall. Bland-Altman analysis revealed best agreement for the birefringence measurements, followed by backscatter intensity, and depolarization, when limiting the analysis to areas of meaningful birefringence. Pearson correlation analysis confirmed highest correlation for birefringence (0.86), preceding backscatter intensity (0.83), and depolarization (0.78). Our results demonstrate that intravascular polarimetry generates robust maps of tissue birefringence and depolarization in a clinical setting. This outcome motivates the use of intravascular polarimetry for future clinical studies that investigate polarization properties of arterial atherosclerosis.