Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels

Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining the role of extracellular cysteines (Cys) in the gating and function of Cx46 hemichannels. We studied Cx46 and mutated all of its extracellular Cys to alanine (Ala) (one at a time) and studied the effects of the Cys mutations on Cx46 expression, localization, and hemichannel activity. Wild-type Cx46 and Cys mutants were expressed at comparable levels, with similar cellular localization. However, functional experiments showed that hemichannels formed by the Cys mutants did not open either in response to membrane depolarization or removal of extracellular divalent cations. Molecular-dynamics simulations showed that Cys mutants may show a possible alteration in the electrostatic potential of the hemichannel pore and an altered disposition of important residues that could contribute to the selectivity and voltage dependency in the hemichannels. Replacement of extracellular Cys resulted in “permanently closed hemichannels”, which is congruent with the inhibition of the Cx46 hemichannel by lipid peroxides, through the oxidation of extracellular Cys. These results point to the modification of extracellular Cys as potential targets for the treatment of Cx46-hemichannel associated pathologies, such as cataracts and cancer, and may shed light into the gating mechanisms of other Cx hemichannels.     

Characterization of Competitive Inhibitors of Plasmodium falciparum cGMP-Dependent Protein Kinase**

Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is an enticing antimalarial drug target. Novel chemotypes are needed because existing inhibitors have safety issues that may prevent further development. This work demonstrates isoxazole-based compounds are potent ATP competitive inhibitors of PfPKG and discloses a new analogue in this series. Isoxazoles 3 and 5 had K_i values that are comparable to a known standard, 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H pyrrol-3-yl] pyridine. They also exhibited excellent selectivity for PfPKG over the human orthologue and the gatekeeper mutant T618Q PfPKG, which mimics the less accessible binding site of the human orthologue. The human orthologue's larger binding site volume is predicted to explain the selectivity of the inhibitors for the P. falciparum enzyme.     

Front-of-package nutrition labeling as a driver for healthier food choices: Lessons learned and future perspectives

This work aims to provide a comprehensive overview of the use of front-of-package nutritional labeling (FOPL), identify and characterize the major existing FOPL systems, examine the impact of FOPL systems on consumer behavior, and discuss future perspectives. The searched databases were PubMed, Scopus, and Web of Science, and papers in English, Portuguese, Spanish, and French were considered. The integrative review method was used, comprising 68 papers. The FOPL system from more than 47 countries from North America, South America, Africa, Europe, Australia, and Asia was included in this study. The two main ways to characterize FOPL are the level of interpretation and the type of information provided. Interpretive schemes (such as warning labels, multiple traffic lights, and Nutri-Score) appear to lead to better consumer understanding and support healthier food purchases. However, due to the differences among the results and the specificity of the contexts in which they are used, it is impossible to define one FOPL interpretation scheme superior to the others. Some potential factors that influence the effectiveness of FOPL on consumer attitudes have been identified, such as food taste, as a major intrinsic factor. Extrinsic factors, such as price, food category, cultural diversity, politics, and economics, were also relevant. The lack of availability of similar alternatives, lack of understanding of the importance of FOPL, and lower levels of income and education were also some cognitive and social aspects impairing FOPL effectiveness. Prospects for the United States, Europe, Brazil, Colombia, and Argentina were discussed.     

Synchrotron‐based microprobe investigation of impurities in raw quartz‐bearing and carbon‐bearing feedstock materials for photovoltaic applications

Using synchrotron‐based analytical microprobe techniques, we determine micrometer‐scale elemental composition, spatial distribution, and oxidation state of impurities in raw feedstock materials used in the photovoltaic industry. Investigated Si‐bearing compounds are pegmatitic quartz, hydrothermal quartz, and quartzite. Micrometer‐scale clusters containing Fe, Ti, and/or Ca are frequently observed at structural defects in oxidized states and in bulk concentrations equivalent to inductively coupled plasma mass spectroscopy measurements. Investigated C‐bearing compounds are pine wood, pine charcoal, and eucalyptus charcoal. Clustered metals are observed only in the charcoal samples. Impurity clustering implies that industrial processing could be adapted to take advantage of this “natural gettering” phenomenon, expanding the usable range of raw feedstock materials to dirtier, cheaper, and more abundant ones, currently underexploited for solar‐grade silicon production. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis of a New Zn2+/Fe3+ Octa(aminopropyl)silsesquioxane Complex and Its Voltammetric Behavior Towards N-acetylcysteine

Silicon - A zinc-modified octa(aminopropyl)silsesquioxane and the cyan compound Na2[Fe(CN)5NO] were prepared to create a hybrid electroactive material (ACZnN) characterized employing the...     

Experimental approaches to study evolutionary cell biology using yeasts

The past century has witnessed tremendous advances in understanding how cells function. Nevertheless, how cellular processes have evolved is still poorly understood. Many studies have highlighted surprising molecular diversity in how cells from diverse species execute the same processes, and advances in comparative genomics are likely to reveal much more molecular diversity than was believed possible until recently. Extant cells remain therefore the product of an evolutionary history that we vastly ignore. Evolutionary cell biology has emerged as a discipline aiming to address this knowledge gap by combining evolutionary, molecular, and cellular biology thinking. Recent studies have shown how even essential molecular processes, such as DNA replication, can undergo fast adaptive evolution under certain laboratory conditions. These developments open new lines of research where the evolution of cellular processes can be investigated experimentally. Yeasts naturally find themselves at the forefront of this research line. Not only do they allow the observation of fast evolutionary adaptation, but they also provide numerous genomic, synthetic, and cellular biology tools already developed by a large community. Here we propose that yeasts can serve as an “evolutionary cell lab” to test hypotheses, principles, and ideas in evolutionary cell biology. We discuss various experimental approaches available for this purpose, and how biology at large can benefit from them.     

Role of Metal Contacts on Halide Perovskite Memristors

Halide perovskites are promising candidates for resistive memories (memristors) due to their mixed electronic/ionic conductivity and the real activation mechanism is currently under debate. In order to unveil the role of the metal contact and its connection with the activation process, four model systems are screened on halide perovskite memristors: Nearly inert metals (Au and Pt), low reactivity contacts (Cu), highly reactive contact (Ag and Al), and pre-oxidized metal in the form of AgI. It is revealed that the threshold voltage for activation of the memory effect is highly connected with the electrochemical activity of the metals. Redox/capacitive peaks are observed for reactive metals at positive potentials and charged ions are formed that can follow the electrical field. Activation proceeds by formation of conductive filaments, either by the direct migration of the charged metals or by an increase in the concentration of halide vacancies generated by this electrochemical reaction. Importantly, the use of pre-oxidized Ag⁺ ions leads to very low threshold voltages of ≈0.2 V indicating that an additional electrochemical reaction is not needed in this system to activate the memristor. Overall, the effect of the metal contact is clarified, and it is revealed that AgI is a very promising interfacial layer for low-energy applications.