Collective and non-collective molecular dynamics in a ferroelectric nematic liquid crystal studied by broadband dielectric spectroscopy

A great deal of effort has been recently devoted to the study of dielectric relaxation processes in ferroelectric nematic liquid crystals, yet their interpretation remains unclear. In this work, we present the results of broadband dielectric spectroscopy experiments of a prototypical ferroelectric nematogen in the frequency range 10 Hz-110 MHz at different electrode separations and under the application of DC bias fields. The results evidence a complex behavior in all phases due to the magnitude of polar correlations in these systems. The observed modes have been assigned to different relaxation mechanisms based on existing theoretical frameworks.Comment: The following article has been submitted to The Journal of Chemical Physics. After it is published, it will be found at https://pubs.aip.org/aip/jc

On the molecular origins of the ferroelectric splay nematic phase

Nematic liquid crystals have been known for more than a century, but it was not until the 60s–70s that, with the development of room temperature nematics, they became widely used in applications. Polar nematic phases have been long-time predicted, but have only been experimentally realized recently. Synthesis of materials with nematic polar ordering at room temperature is certainly challenging and requires a deep understanding of its formation mechanisms, presently lacking. Here, we compare two materials of similar chemical structure and demonstrate that just a subtle change in the molecular structure enables denser packing of the molecules when they exhibit polar order, which shows that reduction of excluded volume is in the origin of the polar nematic phase. Additionally, we propose that molecular dynamics simulations are potent tools for molecular design in order to predict, identify and design materials showing the polar nematic phase and its precursor nematic phases

Dielectric spectroscopy of a ferroelectric nematic liquid crystal and the effect of the sample thickness

The recently discovered ferroelectric nematic liquid crystals have been reported to exhibit very large dielectric permittivity values. Here, we report a systematic investigation of the dielectric behavior of a prototypical ferroelectric nematogen by varying the thickness of the parallel capacitor measuring cell. While in the non-polar high temperature nematic phase results show only slight differences due to slight variations of the alignment, the measured permittivity values in the ferroelectric nematic phase show a linear dependence on the cell thickness. It is also shown that the characteristic relaxation frequency decreases inversely proportionally to the thickness. The results are discussed in terms of three different available models based on different underlying mechanisms, accounting for cancellation of the probe electric fields by polarization reorientation or by ionic charges, or based on a recently proposed continuous phenomenological model

TRPM7 regulates proliferation and polarisation of macrophages.

Ion channels play pivotal roles in regulating important functions of macrophages, such as cytokine and chemokine production, migration, proliferation, phagocytosis and others. In this study, we have identified the transient receptor potential cation channel, subfamily M, member 7 (TRPM7) for the first time in macrophages. TRPM7 activity is differentially regulated in macrophages, i.e. current density in TRPM7 is significantly larger in anti-inflammatory M2-type macrophages than in untreated and in pro-inflammatory M1-type macrophages, whereas mRNA levels of TRPM7 remain unchanged upon cell polarisation. The specific TRPM7 inhibitors NS8593 and FTY720 abolish proliferation of macrophages induced by interleukin-4 (IL-4) and macrophage colony-stimulating factor (M-CSF), respectively, whereas proliferation arrest was not accompanied by induction of apoptosis or necrosis in macrophages. Furthermore, NS8593 and FTY720 prevented polarisation of macrophages towards the anti-inflammatory M2 phenotype. Inhibition of TRPM7 reduced IL-4-induced upregulation of arginase-1 (Arg1) mRNA levels and Arg1 activity, and abolished the inhibitory effects of IL-4 or M-CSF on LPS-induced TNF-α production by macrophages. In summary, our data suggest a main role of TRPM7 in the regulation of macrophage proliferation and polarisation

Organic distributed feedback laser for label-free biosensing of ErbB2 protein biomarker

The human epidermal growth factor receptor 2 (ErbB2) protein plays an important role in human malignancies. Its overexpression has been recognized as a feature of a malignant cancerous phenotype in breast cancer cell lines, and has become one of the most widely investigated clinical indicators of breast, ovarian, gastrointestinal and lung cancers. In this work a vertically emitting organic distributed feedback (DFB) laser has been used to detect the ErbB2 protein. This DFB laser consists of a polystyrene (PS) film containing a perylenediimide laser dye, deposited over a second-order one dimensional grating fabricated on fused silica by thermal-nanoimprint lithography and subsequent reactive ion etching processes. Specificity of the system to ErbB2 protein biomarker, achieved by functionalizing the PS with anti-ErbB2 monoclonal antibodies, is demonstrated. A concentration limit of detection for ErbB2 protein of 14 ng/mL has been obtained, and no cross-reactivity has been observed with bovine serum albumin (BSA) and tumor necrosis factor alpha (TNFα) proteins. These findings open the possibility of using this type of biosensors in clinical applications.This work was supported by the Spanish Government (MINECO) and the European Community (FEDER) through grant no. MAT-2011–28167-C02. This work was partially funded by the Basque Government within the framework of the Etortek Program (Grant No. IE13-360). M. Morales-Vidal has been partly supported by a MINECO FPI fellowship (no. BES-2009-020747)

Organic distributed feedback laser for label-free biosensing of ErbB2 protein biomarker

The human epidermal growth factor receptor 2 (ErbB2) protein plays an important role in human malignancies. Its overexpression has been recognized as a feature of a malignant cancerous phenotype in breast cancer cell lines, and has become one of the most widely investigated clinical indicators of breast, ovarian, gastrointestinal and lung cancers. In this work a vertically emitting organic distributed feedback (DFB) laser has been used to detect the ErbB2 protein. This DFB laser consists of a polystyrene (PS) film containing a perylenediimide laser dye, deposited over a second-order one dimensional grating fabricated on fused silica by thermal-nanoimprint lithography and subsequent reactive ion etching processes. Specificity of the system to ErbB2 protein biomarker, achieved by functionalizing the PS with anti-ErbB2 monoclonal antibodies, is demonstrated. A concentration limit of detection for ErbB2 protein of 14 ng/mL has been obtained, and no cross-reactivity has been observed with bovine serum albumin (BSA) and tumor necrosis factor alpha (TNFα) proteins. These findings open the possibility of using this type of biosensors in clinical applications.This work was supported by the Spanish Government (MINECO) and the European Community (FEDER) through grant no. MAT-2011–28167-C02. This work was partially funded by the Basque Government within the framework of the Etortek Program (Grant No. IE13-360). M. Morales-Vidal has been partly supported by a MINECO FPI fellowship (no. BES-2009-020747)

Macrophages: supportive cells for tissue repair and regeneration.

International audienceMacrophages, and more broadly inflammation, have been considered for a long time as bad markers of tissue homeostasis. However, if it is indisputable that macrophages are associated with many diseases in a deleterious way, new roles have emerged, showing beneficial properties of macrophages during tissue repair and regeneration. This discrepancy is likely due to the high plasticity of macrophages, which may exhibit a wide range of phenotypes and functions depending on their environment. Therefore, regardless of their role in immunity, macrophages play a myriad of roles in the maintenance and recovery of tissue homeostasis. They take a major part in the resolution of inflammation. They also exert various effects of parenchymal cells, including stem and progenitor cell, of which they regulate the fate. In the present review, few examples from various tissues are presented to illustrate that, beyond their specific properties in a given tissue, common features have been described that sustain a role of macrophages in the recovery and maintenance of tissue homeostasis

Acidic residues in the membrane-proximal stalk region of vaccinia virus protein B5 are required for glycosaminoglycan-mediated disruption of the extracellular enveloped virus outer membrane

The extracellular enveloped virus (EEV) form of vaccinia virus (VACV) is surrounded by two lipid envelopes. This presents a topological problem for virus entry into cells, because a classical fusion event would only release a virion surrounded by a single envelope into the cell. Recently, we described a mechanism in which the EEV outer membrane is disrupted following interaction with glycosaminoglycans (GAGs) on the cell surface and thus allowing fusion of the inner membrane with the plasma membrane and penetration of a naked core into the cytosol. Here we show that both the B5 and A34 viral glycoproteins are required for this process. A34 is required to recruit B5 into the EEV membrane and B5 acts as a molecular switch to control EEV membrane rupture upon exposure to GAGs. Analysis of VACV strains expressing mutated B5 proteins demonstrated that the acidic stalk region between the transmembrane anchor sequence and the fourth short consensus repeat of B5 are critical for GAG-induced membrane rupture. Furthermore, the interaction between B5 and A34 can be disrupted by the addition of polyanions (GAGs) and polycations, but only the former induce membrane rupture. Based on these data we propose a revised model for EEV entry

Classical activation of macrophages and vardenafil

Inhibitors of phosphodiesterase 5 (PDE5) - sildenafil citrate (Viagra; Pfizer) and vardenafil hydrochloride (Levitra; Bayer/GlaxoSmithKline) - approved for the treatment of erectile dysfunction and pulmonary arterial hypertension also rescue the loss of cystic fibrosis (CF) chloride channel function and the mislocalization of F508del-CFTR in affected tissues in CF. Can PDE5 inhibitors provide a therapeutic strategy which combines ability to correct the basic ion transport defect and to control de-regulated lung inflammation in CF

Viral Bcl2s' transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis

Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, we show that the carboxyl-terminal hydrophobic region of herpesviral and poxviral vBcl2s can operate as transmembrane domains (TMDs) and participate in their homo-oligomerization. Additionally, we show that the viral TMDs mediate interactions with cellular pro- and anti-apoptotic Bcl2 TMDs within the membrane. Furthermore, these intra-membrane interactions among viral and cellular proteins are necessary to control cell death upon an apoptotic stimulus. Therefore, their inhibition represents a new potential therapy against viral infections, which are characterized by short- and long-term deregulation of programmed cell death