Dramatic Drop in Cell Resistance through Induced Dipoles and Bipolar Electrochemistry

The use of slurries of conducting particles has been considered a way to extend the electrode area in some energy storage electrochemical cells. When suspensions of conducting particles are used in electrolytes a decreased impedance is observed, even for concentrations much lower than the theoretical percolation limits. Indeed, it is known that polarization occurs when a conducting material is immersed in an electrolyte in presence of electric fields, and bipolar electrochemistry processes may occur. This work demonstrates the dramatic drop in resistance for electrochemical cells with just a few macroscopic conducting pieces immersed in the electrolyte, in the absence of any electrical contact, through bipolar induction. Furthermore, mediation of soluble redox species between adjacent induced poles of opposite charge results in an additional mechanism for charge transfer, contributing further to the decrease in impedance. Relevant parameters like size, geometry, and spatial occupation of inducible pieces within the electric field, are relevant. Remarkably, the effects observed can explain some empirical observations previously reported for carbon suspensions and slurries. Thus, no electronic percolation requiring particle contact, nor ordering, are needed to explain the good performance associated to lowered impedance These results suggest new engineering designs for electrochemical cells with enhanced currents

Child attachment in adjusting the species-general contingency between environmental adversities and fast life history strategies

Extrinsic mortality risks calibrating fast life history (LH) represent a species-general principle that applies to almost all animals including humans. However, empirical research also finds exceptions to the LH principle. The present study proposes a maternal socialization hypothesis, whereby we argue that the more human-relevant attachment system adds to the LH principle by up- and down-regulating environmental harshness and unpredictability and their calibration of LH strategies. Based on a longitudinal sample of 259 rural Chinese adolescents and their primary caregivers, the results support the statistical moderating effect of caregiver–child attachment on the relation between childhood environmental adversities (harshness and unpredictability) and LH strategies. Our theorizing and findings point to an additional mechanism likely involved in the organization and possibly the slowdown of human LH.

PCBP1 Deficient Pigs Hold the Potential to Inhibit CSFV Infection

Classical swine fever virus (CSFV), pathogen of classic swine fever, has caused severe economic losses worldwide. Poly (rC)-binding protein 1 (PCBP1), interacting with Npro of CSFV, plays a vital role in CSFV growth. Here, our research is the first report to generate PCBP1 knockout pigs via gene editing technology. The PCBP1 knockout pigs exhibited normal birth weight, reproductive-performance traits, and developed normally. Viral challenge results indicated that primary cells isolated from F0 and F1 generation pigs could significantly reduce CSFV infection. Additional mechanism exploration further confirmed that PCBP1 KO mediated antiviral effect is related with the activation of type I interferon. Beyond showing that gene editing strategy can be used to generate PCBP1 KO pigs, our study introduces a valuable animal model for further investigating infection mechanisms of CSFV that help to develop better antiviral solution.

Oblique differential object marking and types of nominals

The question of whether differentially marked objects should be linked with Case licensing or some other mechanism in the grammar has given rise to numerous debates. Addressing contexts of differential object marking (DOM) with oblique morphology, this article shows that, while the Case licensing approach might be adequate for varieties of Spanish, oblique differential marking rather signals an independent licensing operation, beyond Case, in languages like Romanian, Gujarati or Mandarin Chinese. This additional mechanism, relevant at the syntax-semantics-pragmatics interface, tracks the role of grammaticalized animates or how the speaker relates to other entities in the discourse. Additionally, the data examined here indicate that objects can come in a variety of sizes and structures, with distinct licensing constraints, such that the divide Case licensed/unlicensed or Case licensing/(pseudo-)incorporation is not enough.

Investigation of Non-Newtonian Fluid Behavior and Coefficient of Friction in Water Hammer Phenomena

An unstable flow of non-Newtonian fluid, with friction in a pipe is studied, describing the water hammer phenomenon. The equations of the problem are given, then solved by a numerical approach. The non-Newtonian behavior of the fluid, as well as the effect of the coefficient of friction which represents an additional mechanism of energy dissipation are investigated. The 1D and 2D problem is used simultaneously, based on the Runge-kutta method for the descritization in time, Finite differences, Characteristics for the descritization in space. The results of this article show by verifying with experience that these methods used, in addition to being simple, are also effective and give reasonable results.

Probing tricarbocyanine dyes for targeted delivery of anthracyclines

Heptamethine carbocyanine dyes possess bright fluorescence in the near IR range and affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery in their covalent conjugates with cytotoxic compounds. In this work we synthesized four drug-dye conjugates of tricarbocyanine dyes with anthracycline drug daunorubicin using a CuAAC reaction. Conjugates with hydrophobic dyes possess submicromolar cytotoxicity. Fluorescent imaging revealed significant accumulation of the conjugates in mitochondria, suggesting an enhancement of an additional mechanism of anthracycline cytotoxicity – generation of ROS. The hypothesis was supported by significant reduction of activity of the conjugates in presence of an antioxidant compound.

A novel mechanism of thrombocytopenia by PS exposure through TMEM16F in sphingomyelin synthase 1 deficiency

Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Here, we describe the hematologic phenotypes, such as reduced circulating platelets and dysfunctional hemostasis, in SMS1-deficient (SMS1-KO) mice. SMS1-KO mice display pathologic manifestations related to idiopathic thrombocytopenia (ITP), including relatively high amounts of peripheral blood reticulated platelets, enhanced megakaryopoiesis in the bone marrow and spleen, and splenomegaly. Deficiency of SMS1, but not SMS2, prevented SM production and enhanced phosphatidylserine (PS) externalization on the plasma membranes of platelets and megakaryocytes. Consequently, SMS1-KO platelets were excessively cleared by macrophages in the spleen. Multimer formation in the plasma membrane of TMEM16F, a known calcium (Ca2+)-activated nonselective ion channel and Ca2+-dependent PS scramblase, was enhanced; the result was PS externalization to outer leaflets through increased Ca2+ influx in immortalized mouse embryonic fibroblasts established from SMS1-KO mice (SMS1-KO tMEFs), as seen with SMS1-KO platelets. Thus, SMS1 deficiency changed the TMEM16F distribution on the membrane microdomain, regulating Ca2+ influx-dependent PS exposure. SMS1-KO tMEFs in which TMEM16F was knocked out by using the CRISPR/Cas9 system lacked both the Ca2+ influx and excess PS exposure seen in SMS1-KO tMEFs. Therefore, SM depletion on platelet membrane microdomains due to SMS1 deficiency enhanced PS externalization via a Ca2+ influx through TMEM16F activation, leading to elevated platelet clearance and causing hemostasis dysfunction through thrombocytopenia. Our current findings show that the SM-rich microdomain generated by SMS1 is a potent regulator of thrombocytopenia through TMEM16F, suggesting that its dysfunction may be a novel additional mechanism of ITP.

Kinetochore-bound Mps1 regulates kinetochore–microtubule attachments via Ndc80 phosphorylation

Dividing cells detect and correct erroneous kinetochore–microtubule attachments during mitosis, thereby avoiding chromosome missegregation. The Aurora B kinase phosphorylates microtubule-binding elements specifically at incorrectly attached kinetochores, promoting their release and providing another chance for proper attachments to form. However, growing evidence suggests that the Mps1 kinase is also required for error correction. Here we directly examine how Mps1 activity affects kinetochore–microtubule attachments using a reconstitution-based approach that allows us to separate its effects from Aurora B activity. When endogenous Mps1 that copurifies with kinetochores is activated in vitro, it weakens their attachments to microtubules via phosphorylation of Ndc80, a major microtubule-binding protein. This phosphorylation contributes to error correction because phospho-deficient Ndc80 mutants exhibit genetic interactions and segregation defects when combined with mutants in other error correction pathways. In addition, Mps1 phosphorylation of Ndc80 is stimulated on kinetochores lacking tension. These data suggest that Mps1 provides an additional mechanism for correcting erroneous kinetochore–microtubule attachments, complementing the well-known activity of Aurora B.

Clusters of neuronal Neurofascin prefigure node of Ranvier position along single axons

The spacing of nodes of Ranvier crucially affects conduction properties along myelinated axons. It has been assumed that node position is primarily driven by the growth of myelin sheaths. Here, we reveal an additional mechanism of node positioning that is driven by the axon. We show through longitudinal live imaging of node formation dynamics that stable clusters of the cell adhesion molecule Neurofascin A accumulate at specific sites along axons prior to myelination. While some of these clusters change position upon encounter with growing myelin sheaths, others restrict sheath extension and are therefore predictive of future node position. Animals that lack full-length Neurofascin A showed increased internodal distances and less regular spacing of nodes along single axons. Together, our data reveal the existence of an axonal mechanism to position its nodes of Ranvier that does not depend on regulation of myelin sheath length.

Therapeutic Properties of Highly Selective β-blockers With or Without Additional Vasodilator Properties: Focus on Bisoprolol and Nebivolol in Patients With Cardiovascular Disease

Bisoprolol and nebivolol are highly selective β1-adrenoceptor antagonists, with clinical indications in many countries within the management of heart failure with reduced left ventricular ejection fraction (HFrEF), ischaemic heart disease (IHD), and hypertension. Nebivolol has additional vasodilator actions, related to enhanced release of NO in the vascular wall. In principle, this additional mechanism compared with bisoprolol might lead to more potent vasodilatation, which in turn might influence the effectiveness of nebivolol in the management of HFrEF, IHD and hypertension. In this article, we review the therapeutic properties of bisoprolol and nebivolol, as representatives of “second generation” and “third generation” β-blockers, respectively. Although head-to-head trials are largely lacking, there is no clear indication from published studies of an additional effect of nebivolol on clinical outcomes in patients with HFrEF or the magnitude of reductions of BP in patients with hypertension.