Assessment of Tractable Cysteines for Covalent Targeting by Screening Covalent Fragments

Targeted covalent inhibition and the use of irreversible chemical probes are important strategies in chemical biology and drug discovery. To date, the availability and reactivity of cysteine residues amenable for covalent targeting have been evaluated by proteomic and computational tools. Herein, we present a toolbox of fragments containing a 3,5-bis(trifluoromethyl)phenyl core that was equipped with chemically diverse electrophilic warheads showing a range of reactivities. We characterized the library members for their reactivity, aqueous stability and specificity for nucleophilic amino acids. By screening this library against a set of enzymes amenable for covalent inhibition, we showed that this approach experimentally characterized the accessibility and reactivity of targeted cysteines. Interesting covalent fragment hits were obtained for all investigated cysteine-containing enzymes.     

Effect of Compression with Oscillatory Torsion Processing on Structure and Properties of Cu

The results presented in this study were concerned with microstructures and mechanical properties of polycrystalline Cu subjected to plastic deformation by a compression with oscillatory torsion process. Different deformation parameters of the compression with oscillatory torsion process were adopted to study their effects on the microstructure and mechanical properties. The deformed microstructure was characterized quantita- tively by electron backscattered diffraction (EBSD) and scanning transmission electron microscopy (STEM). Mechanical properties were determined on an MTS QTest/10 machine equipped with digital image correlation. From the experimental results, processes performed at high compression speed and high torsion frequency are recommended for refining the grain size. The size of structure elements, such as average grain size (D) and subgrain size (d), reached 0.42 μm and 0.30 μm, respectively, and the fraction of high angle boundaries was 35% when the sample was deformed at a torsion frequency f = 1.6 Hz and compression rate v = 0.04 mm/s. These deformation parameters led to an improvement in the strength properties. The material exhibited an ultimate tensile strength (UTS) of 434 MPa and a yield strength (YS) of 418 MPa. These values were about two times greater than those of the initial state.     

Poly(ε-caprolactone)-based membranes with tunable physicochemical,bioactive and osteoinductive properties

In contrast to currently used materials, membranes for the treatment of bone defects should actively promote regeneration of bone tissue beyond their physical barrier function. What is more, both material properties and biological features of membranes should be easily adaptable to meet the needs of particular therapeutic applications. Therefore, the role of preparation methods (non-solvent-induced phase separation and thermal-induced phase separation) of poly(ε-caprolactone)-based membranes and their modification with gel-derived bioactive glass (BG) particles of two different sizes (<45 and <3 μm) in modulating material morphology, polymer matrix crystallinity, surface wettability, kinetics of in vitro bioactivity and also osteoblast response was investigated. Both surfaces of membranes were characterised in terms of their properties. Our results indicated a possibility to modulate microstructure (pore size ranging from submicron to hundreds of micrometres), wettability (from hydrophobic to fully wettable surface) and polymer crystallinity (from 19 to 60%) in a wide range by the use of various preparation methods and different BG particle sizes. Obtained composite membranes showed excellent in vitro hydroxyapatite forming ability after incubation in simulated body fluid. Here we demonstrated that bioactive layer formation on the surface of membranes occurred through ACP–OCP–CDHA–HCA transformation, that mimic in vivo bone biomineralization process. Composite membranes supported human osteoblast proliferation, stimulated cell differentiation and matrix mineralization. We proved that kinetics of bioactivity process and also osteoinductive properties of membranes can be easily modulated with the use of proposed variables. This brings new opportunities to obtain multifunctional membranes for bone regeneration with tunable physicochemical and biological properties.     

Lithography‐Free Fabrication of Silica Nanocylinders with Suspended Gold Nanorings for LSPR‐Based Sensing

Tunable plasmonic platforms are important for a variety of applications such as photovoltaics, LED's, optoelectronics, medical research, and biosensors. In particular, development of label‐free plasmonic biosensors is one of the key research areas that utilizes plasmonic nanostructures for detection of biologically relevant molecules at low concentrations. The authors have developed a cost‐effective, fast, and lithography‐free method to fabricate transparent fused silica nanocylinders. The technique allows tuning of nanocylinder height, diameter, and density and can be scaled to large surface areas, such as 8 in. wafers. The authors demonstrate that gold coated nanocylinders support localized surface plasmon resonances (LSPR) from visible to near infrared wavelengths. The plasmonic platform can be characterized as suspended gold nanorings and exhibits a sensitivity of 658 nm RIU^–1 with a figure‐of‐merit of 10, comparable to other state‐of‐the‐art LSPR sensing platforms that utilize more complex nanofabrication pathways. It was observed that the LSPR peak positions can be controlled by varying the geometry of the nanocylinders. The authors illustrate surface functionalization, biosensing, and surface regeneration properties of the platform using thiols and detection of bovine serum albumin (BSA). The observed LSPR shifts for 11‐mercaptoundecanoic acid and BSA was 12 and 26 nm, respectively.     

HIV and Proteomics: What We Have Learned from High Throughput Studies

The accelerated development of technology over the last three decades has driven biological sciences to high-throughput profiling experiments, now broadly referred to as systems biology. The unprecedented improvement of analytical instrumentation has opened new avenues for more complex experimental designs and expands the knowledge in genomics, proteomics, and other omics fields. Despite the collective efforts of hundreds of researchers, gleaning all the expected information from omics experiments is still quite far. This paper summarizes what has been learned from high-throughput proteomics studies thus far, and what is believed should be done to reveal even more valuable information from such studies. It is drawn from the background in using proteomics to study human immunodeficiency virus 1 infection of macrophages and/or T cells, but it is believed that some conclusions will be more broadly applicable.     

Stresses Generated During Convective and Microwave Drying

Abstract

An outline of the mechanistic model of convective and microwave drying of saturated capillary-porous materials is presented. The model was derived in the framework of irreversible thermodynamics. Particular attention is devoted to construction of the term describing the power of microwave radiation absorbed per unit volume, which is converted into internal heat source. The qualitative difference in distribution of temperature, moisture content, and the drying-induced stresses in materials under convective and microwave drying is illustrated in the examples of cylindrical kaolin samples. The diagrams of acoustic emission are taken off on-line from these samples in order to illustrate the development of material destruction caused by the stresses induced during both convective and microwave drying.     

Silica functionalized by pyridinecarboximidamides as a novel sorbent of heavy metals ions

ABSTRACT

Two novel sorbents, obtained as a result of surface modification of silica gel for the Cu(II), Co(II) and Ni(II) removal from aqueous solutions were proposed. For the modification, 3-chloropropyltrimethoxysilane, N’-hydroxy-N,N-dioctylpyridine-3-carboximidamide and N’-hydroxy-N,N-dioctylpyridine-4-carboximidamides were used. A series of basic tests on the sorption of Cu(II), Co(II) and Ni(II) were carried out and the presented results indicated that the novel sorbents were able to remove all tested metals ions from the aqueous solutions, and the removal efficiency was dependent on the functionalised agent structure, dosage, metal ions concentration and pH. The Langmuir model also assumed that a monolayer sorption occurred.     

Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.