Pull-Down of Metalloproteins in Their Native States by Using Desthiobiotin-Based Probes

One-third of all proteins are estimated to require metals for structural stability and/or catalytic activity. Desthiobiotin probes containing metal binding groups can be used to capture metalloproteins with exposed active-site metals under mild conditions so as to prevent changes in metallation state. The proof-of-concept was demonstrated with carbonic anhydrase (CA), an open active site, Zn²⁺-containing protein. CA was targeted by using sulfonamide derivatives. Linkers of various lengths and structures were screened to determine the optimal structure for capture of the native protein. The optimized probes could selectively pull down CA from red blood cell lysate and other protein mixtures. Pull-down of differently metallated CAs was also investigated.     

Evaluation of Intellectual Property Objects in the Nanoindustry Field

Russian Microelectronics - The recently developed nanomaterials and their production technologies as intellectual property objects (IPOs) are considered. The role of the informational-analytical...     

The Influence of the Sequence of Application of Modifying Components on the Protective Properties of a Chemical Ammonia Absorber

Protection of Metals and Physical Chemistry of Surfaces - In this work, a universal sorbent has been obtained that works according to the mechanisms of chemisorption and adsorption by impregnating...     

Untapped Knowledge about Water Reuse: the Roles of Direct and Indirect Educational Messaging

Water Resources Management - Public awareness of water quality concerns has increased since the Flint, MI crisis, but knowledge about water resources management remains low. Consequently,...     

Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

Analysis and optimization of noises of an analog circuit via PSO algorithms

Microsystem Technologies - The strategy for analysis of noise generated in the analog circuit is presented here. Further, methodology for optimization of noise to improve the performance of the...     

Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

Skeletal Muscle Health and Cognitive Function: A Narrative Review

Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting skeletal muscle is a major source of neurotrophic factors, including brain-derived neurotrophic factor, which regulate synapses in the brain. Furthermore, skeletal muscle activity has important immune and redox effects that modify brain function and reduce muscle catabolism. The identification of common risk factors and underlying mechanisms for sarcopenia and cognition may allow the development of targeted interventions that slow or reverse sarcopenia and also certain forms of cognitive decline. However, the links between cognition and skeletal muscle have not been elucidated fully. This review provides a critical appraisal of the literature on the relationship between skeletal muscle health and cognition. The literature suggests that sarcopenia and cognitive decline share pathophysiological pathways. Ageing plays a role in both skeletal muscle deterioration and cognitive decline. Furthermore, lifestyle risk factors, such as physical inactivity, poor diet and smoking, are common to both disorders, so their potential role in the muscle–brain relationship warrants investigation.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Decorative near-infrared transmission filters featuring high-efficiency and angular-insensitivity employing 1D photonic crystals

We present a new scheme for visibly-opaque but near-infrared-transmitting filters involving 7 layers based on one-dimensional ternary photonic crystals, with capabilities in reaching nearly 100% transmission efficiency in the near-infrared region. Different decorative reflection colors can be created by adding additional three layers while maintaining the near-infrared transmission performance. In addition, our proposed structural colors show great angular insensitivity up to ±60° for both transverse electric and transverse magnetic polarizations, which are highly desired in various fields. The facile strategy described here involves a simple deposition method for the fabrication, thereby having great potential in diverse applications such as image sensors, anti-counterfeit tag, and optical measurement systems.