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Protein phosphatase 2A (PP2A) is one of the most ubiquitous cellular proteins and is responsible for the vast majority of Ser/Thr phosphatase activity in eukaryotes. PP2A is a heterotrimer, and its assembly, intracellular localization, enzymatic activity, and substrate specificity are subject to dynamic regulation. Each of its subunits can be targeted by viral proteins to hijack and modulate its activity and downstream signaling to the advantage of the virus. Binding to PP2A is known to be essential to the life cycle of many viruses and seems to play a particularly crucial role for oncogenic viruses, which utilize PP2A to transform infected cells through controlling the cell cycle and apoptosis. Here we summarise the latest developments in the field of PP2A viral targeting; in particular recent discoveries of PP2A hijacking through molecular mimicry of a B56-specific motif by several different viruses. We also discuss the potential as well as shortcomings for therapeutic intervention in the face of our current understanding of viral PP2A targeting. [ABSTRACT FROM AUTHOR]

The ordering kinetics of directed assembly of cylinder-forming diblock copolymers is investigated by cell dynamics simulation of the time-dependent Ginzburg-Landau theory. The directing field, mimicking chemically or topologically patterned surfaces, is composed of a rectangular array of potential wells which are attractive to the minority blocks. The period of the templating fields is commensurate with the hexagonal lattice of the block copolymer domains. The ordering kinetics is described by the time evolution of the defect concentration, which reveals that the rectangular field of [1 m] for a given density multiplication has the best directing effect, and the reversed case of [m 1] has the worst. Compared with a hexagonal directing field, the rectangular field provides a better directing efficiency for a fixed high density multiplication. The difference of the directing effect can be understood by analyzing the ordering mechanisms in the two types of directing fields. The study reveals that the rectangular pattern is an alternative candidate to direct block copolymer assembly toward large-scale ordered domains. [ABSTRACT FROM AUTHOR]

The article discusses the matching of dental implant’s fluorescence with the fluorescence of the natural teeth as one of the main aspect of esthetic restorative dentistry. It presents information on the first findings on the natural teeth’s fluorescence and dentin as the major content to provide them fluorescence. The article further states that modern composite resins contain fluorescent pigments, porcelains for veneering and ceramics copying materials such as alumina are used for mimicking the optical quality of the natural teeth. It also states that zirconia is considered as one of the best implant abutments due to its colour availability and ability of preventing the grayish appearance of the surrounding soft tissues.

We present an approach to mimic replica exchange molecular dynamics simulations (REMD) on a microsecond time scale within a few minutes rather than the years, which would be required for real REMD. The speed of mimicked REMD makes it a useful tool for “testing” the efficiency of different settings for REMD and then to select those settings, that give the highest efficiency. We present an optimization approach with the example of Hamiltonian REMD using soft-core interactions on two model systems, GTP and 8-Br-GTP. The optimization process using REMD mimicking is very fast. Optimization of Hamiltonian-REMD settings of GTP in explicit water took us less than one week. In our study we focus not only on finding the optimal distances between neighboring replicas, but also on finding the proper placement of the highest level of softness. In addition we suggest different REMD simulation settings at this softness level. We allow several replicas to be simulated at the same Hamiltonian simultaneously and reduce the frequency of switching attempts between them. This approach allows for more efficient conversions from one stable conformation to the other. [ABSTRACT FROM AUTHOR]

An amphoteric phenolic compound with carboxyl and amino functional groups was synthesized and used as mimic glucose isomerase to catalyze the isomerization of glucose into fructose. The mimic enzyme displayed excellent catalytic activity for isomerization of glucose to fructose under mild conditions. The yield of fructose and selectivity of fructose could reach 33.0 % and 93.5 % after reacting 4 h, respectively, at pH 8.5 and 80 °C. The catalysis reaction rate constant kcat and Michaelis constants KmG, KmF were calculated. The activation energy of glucose to fructose was evaluated as 65.9 kJ mol−1. The possible catalysis reaction mechanism was proposed. The acid‐base groups on the catalyst play an important role in proton extraction and transfer, as well as in the rotation of local carbon chain, which leads to the highly selective isomerization of glucose into fructose under mild conditions. [ABSTRACT FROM AUTHOR]

Enzyme mimics have broad applications in catalysis and can assist elucidation of the catalytic mechanism of natural enzymes. However, challenges arise from the design of catalytic sites, the selection of host molecules, and their integration into active three‐dimensional structures. Herein, we describe the development of a photooxidase mimic by synergetic molecular self‐assembly. 9‐Fluorenylmethyloxycarbonyl‐l‐histidine undergoes efficient co‐assembly with phthalocyanine into nanovesicles with tunable particle size and membrane thickness. The obtained nanovesicles can be used as catalysts for reactive‐oxygen‐mediated photosensitive oxidation with improved efficiency and stability. This work highlights the co‐assembly of simple building blocks into a supramolecular photocatalyst, which might give insight into possible evolutionary paths of photocatalytic membrane systems, and might allow facile transfer into photosensitive nanoreactors or artificial organelles. [ABSTRACT FROM AUTHOR]

Hollow, porous NiS nanocubes were prepared by a hydrothermal method starting from Ni-Co Prussian blue analogue nanocubes as the template. The morphology and structure of the NiS nanocubes were tuned by adjustment of the ion-exchange rate and the degree of chemical etching, and they were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, and nitrogen sorption measurements. The NiS nanocubes are shown to act as a peroxidase mimic that can catalyze the oxidization of 3,3′,5,5′-tetramethylbenzidine by hydrogen peroxide (H2O2), producing a visible color change, for which the absorbance is best measured at 652 nm. The outstanding activity may result from the unique structure of the NiS nanocubes. The catalytic oxidation follows Michaelis-Menten kinetics and shows a ping-pong mechanism of enzyme action. The findings were used to develop a rapid, sensitive, and selective colorimetric H2O2 assay with a response that is linear in the 4-40 μM range with a detection limit of 1.72 μM (signal-to-noise ratio of 3).ᅟ [ABSTRACT FROM AUTHOR]

Abstract To substantially simplify the fabrication of analytical devices for rapid screening tests, in this study we employed multi-material fused deposition modeling-type three-dimensional printing (3DP) and two functionalized thermoplastic filaments—acrylonitrile butadiene styrene (ABS) incorporating peroxidase-mimicking iron oxide (Fe 3 O 4) nanoparticles and polyvinyl alcohol (PVA) infiltrated with the chromogenic substrate o -phenylenediamine (OPD)—for the one-step manufacture of enzyme/substrate–incorporated multi-well plates. Upon contact with samples, these fabricated devices (i) released the chromogenic substrate OPD into the solution, (ii) efficiently catalyzed the oxidation of OPD mediated by the peroxidase substrate H 2 O 2 , (iii) enabled assays of those substances availably oxidized by their specific oxidases to generate H 2 O 2 , and (iv) facilitated colorimetric observation by the naked eye or through absorbance measurements after loading into a microplate reader. With glucose oxidase immobilized in each well, samples appropriately diluted could be directly loaded for derivatizing and analyzing glucose without adding any other reagents. After assay optimization, the limits of detection reached as low as 2.8 μM for H 2 O 2 and 5.0 μM for glucose; the method's applicability was illustrated in terms of determining glucose concentrations in urine, serum, and plasma samples. These 3D-printed peroxidase mimic/chromogenic substrate–incorporated multi-well plates appear to be highly suitable for rapid and high-throughput screening of glucose in clinical samples. We demonstrate that adequate functionalization of raw materials for 3DP can contribute to the development of novel multifunctional devices with many potential practical applications. Graphical abstract Image 1 Highlights • Fe 3 O 4 NP–incorporated ABS and OPD–infiltrated PVA were respectively optimized. • Enzyme/substrate–incorporated multi-well plates were one-step fabricated by 3DP. • Well diluted samples were analyzed simply after directly loading into these devices. • The method's detection limits reached 2.8 μM for H 2 O 2 and 5.0 μM for glucose. • These devices were highly applicable for rapid glucose screening in clinical samples. [ABSTRACT FROM AUTHOR]

The present study describes the first example of the stoichiometric and catalytic oxidation of flavanone by synthetic nonheme oxoiron(iv) complexes and their precursor iron(ii) complexes with m-CPBA as the terminal oxidant. These models, including detailed kinetic, mechanistic and computational studies, may serve as the biomimics of flavone synthase (FS) enzymes. [ABSTRACT FROM AUTHOR]

The cavities of metallosupramolecular cages can be used to mimic the central spaces of naturally occurring proteins and bind a wide variety of molecular guests. A range of potential applications have arisen from this capacity for host–guest chemistry. However, to truly harness the opportunities thus afforded, methodologies to controllably allow the release and reuptake of guests from the cavities of metallosupramolecular cages are required. Methods to accomplish this have centered upon reversibly altering the character of either the guest or host. This minireview outlines the current approaches used to carry out the binding and release of guests from metallosupramolecular hosts using important examples from the field. The cavities of metallosupramolecular cages can be used to mimic the central spaces of naturally occurring proteins and bind a wide variety of molecular guests. However, in order to more fully mimic Nature mechanisms that allow for the binding and release of guest molecules are required. This minireview outlines the current approaches used to carry out the binding and release of guests from metallosupramolecular hosts. [ABSTRACT FROM AUTHOR]

A novel significant colorimetric sensor has been developed for the selective detection of Hg(II) ions based on Fe 3 O 4 @ZnO nanocomposite as peroxidase mimics. We have successfully synthesized nanocomposite by solvothermal method and it is characterized by analytical technique using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and vibrating sample magnetometry. This nanocomposite exhibits a peroxidase mimetic activity that could efficiently catalyze the oxidation of tetramethylbenzidine (TMB) in the presence of H 2 O 2 to form blue colored cation radical. In addition, the biomolecule of Cysteine (Cys) easily hinder the cation radical formation and turns back TMB molecules into colourless. Whereas the Hg(II) ion, having strong affinity to thiol group easily binds with Cys. As a result of it, the blue colour of the solution is recovered in presence of Fe 3 O 4 @ZnO nanocomposite. Based on this mechanism, we have developed a simple and rapid colorimetric detection of Hg 2+ ions, which is found to be 23 nM. Furthermore, the colorimetric sensor has been applied to detect Hg 2+ in real water samples and find convenient potential applications in the biological and environmental field. [ABSTRACT FROM AUTHOR]

Despite the relevant biological functions of heparan sulfate (HS) glycosaminoglycans, their limited availability and the chemical heterogeneity from natural sources hamper their use for biomedical applications. Chitosan sulfates (ChS) exhibit structural similarity to HSs and may mimic their biological functions. We prepared a variety of ChS with different degree of sulfation to evaluate their ability to mimic HS in protein binding and to promote neural cell division and differentiation. The structure of the products was characterized using various spectroscopic and analytical methods. The study of their interaction with different growth factors showed that ChS bound to the proteins similarly or even better than heparin. In cell cultures, a transition effect on cell number was observed as a function of ChS concentration. Differences in promoting the expression of the differentiation markers were also found depending on the degree of sulfation and modification in the chitosan. [ABSTRACT FROM AUTHOR]

Bacterial infection continues to be a growing global health problem with the most widely accepted treatment paradigms restricted to antibiotics. However, antibiotics overuse and misuse have triggered increased multidrug resistance, frustrating the therapeutic outcomes and leading to higher mortalities. Even worse, the tendency of bacteria to form biofilms on living and nonliving surfaces further increases the difficulty in confronting bacteria because the extracellular matrix can act as a robust barrier to prevent the penetration of antibiotics and resist environmental stress. As a result, the inability to completely eliminate bacteria and biofilms often leads to persistent infection, implant failure, and device damage. Therefore, it is of paramount importance to develop alternative antimicrobial agents while avoiding the generation of bacterial resistance. Taking lessons from natural enzymes for destroying cellular structural integrity or interfering with metabolisms such as proliferation, quorum sensing, and programmed death, the construction of artificial enzymes to mimic the enzyme functions will provide unprecedented opportunities for combating bacteria. Moreover, compared to natural enzymes, artificial enzymes possess much higher stability against stringent conditions, easier tunable catalytic activity, and large-scale production for practical use. In this Account, we will focus on our recent progress in the design and synthesis of artificial enzymes as a new generation of "antibiotics", which have been demonstrated as promising applications in planktonic bacteria inactivation, wound/lung disinfection, as well as biofilm inhibition and dispersion. First, we will introduce direct utilization of the intrinsic catalytic activities of artificial enzymes without dangerous chemical auxiliaries for killing bacteria under mild conditions. Second, to avoid the toxicity caused by overdose of H2O2 in conventional disinfections, we leveraged artificial enzymes with peroxidase-mimic activities to catalyze the generation of hydroxyl radicals at low H2O2 levels while achieving efficient antibacterial outcomes. Importantly, the feasibility of these artificial enzymes was further demonstrated in vivo by mitigating mice wound and lung disinfection. Third, by combining artificial enzymes with stimuli-responsive materials, smart on-demand therapeutic modalities were constructed for thwarting bacteria in a controllable manner. For instance, a photoswitchable "Band-Aid"-like hydrogel doped with artificial enzymes was developed for efficiently killing bacteria without compromising mammal cell proliferation, which was promising for accelerating wound healing. Lastly, regarding the key roles that extracellular DNAs (eDNAs) play in maintaining biofilm integrity, we further designed a multinuclear metal complex-based DNase-mimetic artificial enzyme toward cleaving the eDNA for inhibiting biofilm formation and dispersing the established biofilms. We expect that our rational designs would boost the development of artificial enzymes with different formulations as novel antibacterial agents for clinical and industrial applications. [ABSTRACT FROM AUTHOR]

For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the rate of implant formation plays an important role in determining the overall drug release kinetics. Currently, in vitro techniques capable of characterizing the processes of drug release and implant formation at the same time are not available. A hydrogel-based in vitro experimental setup was recently developed requiring only microliter of formulation and forming a closed system potentially suitable for interfacing with various spectroscopic techniques. The aim of the present proof-of-concept study was to investigate the feasibility of concomitant UV imaging, Vis imaging and light microscopy for detailed characterization of the behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the subcutis. The model compounds, piroxicam and α-lactalbumin were added to PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA-solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and light microscopy were applied to visualize the depot formation and UV imaging was used to quantify drug transport in the hydrogel. As compared to piroxicam, the α-lactalbumin invoked an acceleration of phase separation and an increase of implant size. α-Lactalbumin was released faster from the PLGA-1-methyl-2-pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam release pattern. A linear relationship between the rate of implant formation and initial compound release within the first 4 h was established for the PLGA-NMP systems. This implies that phase separation may be one of the controlling factors in drug release. The rate of implant formation may be an important parameter for predicting and tailoring drug release. The approach combining UV imaging, Vis imaging and light microscopy may facilitate understanding of release processes and holds potential for becoming a useful tool in formulation development of in situ forming implants. [ABSTRACT FROM AUTHOR]

L-type voltage-gated CaV1.2 calcium channels (CaV1.2) are key regulators of neuronal excitability, synaptic plasticity, and excitation-transcription coupling. Surface-exposed CaV1.2 distributes in clusters along the dendrites of hippocampal neurons. A permanent exchange between stably clustered and laterally diffusive extra-clustered channels maintains steady-state levels of CaV1.2 at dendritic signaling domains. A dynamic equilibrium between anchored and diffusive receptors is a common feature among ion channels and is crucial to modulate signaling transduction. Despite the importance of this fine regulatory system, the molecular mechanisms underlying the surface dynamics of CaV1.2 are completely unexplored. Here, we examined the dynamic states of CaV1.2 depending on phosphorylation on Ser- 1700 and Ser-1928 at the channel C terminus. Phosphorylation at these sites is strongly involved in CaV1.2-mediated nuclear factor of activated T cells (NFAT) signaling, long-term potentiation, and responsiveness to adrenergic stimulation. We engineered CaV1.2 constructs mimicking phosphorylation at Ser-1700 and Ser-1928 and analyzed their behavior at the membrane by immunolabeling protocols, fluorescence recovery after photobleaching, and single particle tracking. We found that the phosphomimetic S1928E variant increases the mobility of CaV1.2 without altering the steady-state maintenance of cluster in young neurons and favors channel stabilization later in differentiation. Instead, mimicking phosphorylation at Ser- 1700 promoted the diffusive state of CaV1.2 irrespective of the differentiation stage. Together, these results reveal that phosphorylation could contribute to the establishment of channel anchoring mechanisms depending on the neuronal differentiation state. Finally, our findings suggest a novel mechanism by which phosphorylation at the C terminus regulates calcium signaling by tuning the content of CaV1.2 at signaling complexes. [ABSTRACT FROM AUTHOR]

Background and aims Periodontitis, a common polymicrobial inflammatory disease in the tooth supporting tissues, is a risk factor for coronary artery disease. One of the proposed underlying mechanisms is the systemic immune response to periodontal infection. We studied how serum antibodies against seven periodontal pathogens and their subgingival levels associate with each other, periodontitis, and coronary artery disease. Methods The Parogene cohort included 505 Finnish patients (mean age 63 y) who underwent coronary angiography, and clinical and radiographic oral examinations. Coronary diagnosis was defined as no significant coronary artery disease (<50% stenosis, n = 152), stable coronary artery disease (≥50% stenosis, n = 184) and acute coronary syndrome (n = 169). Levels of subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Tannerella forsythia, Campylobacter rectus, and Fusobacterium nucleatum were determined by checkerboard DNA-DNA hybridization. Serum antibody (IgA/IgG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Aggregate IgA/IgG burdens were calculated by summing and standardizing the serum antibody levels. Results Patients with active periodontitis were characterized by higher levels of subgingival bacteria and corresponding IgA/IgG response. Quartiles 2–4 of serum IgA/IgG burden indicated higher risk for acute coronary syndrome (OR 1.84, 95%CI 1.01–3.35 for IgA; OR 1.87, 95%CI 1.01–3.46 for IgG) independently of established cardiovascular risk factors, body mass index, number of teeth, subgingival bacterial levels and periodontal diagnosis. Conclusions Our findings support the hypothesis that the association between periodontitis and cardiovascular diseases is partly mediated by the immunologic response for periodontal pathogens. [ABSTRACT FROM AUTHOR]

This article provides an overview of the efforts toward the synthesis of nucleoside polyphosphate mimics featuring a P-CXY-P scaffold. The following synthetic approaches to these compounds are summarized: (i) nucleophilic displacement of 5'-O-tosyl nucleoside by the ammonium salts of methylenebisphosphonic acid; (ii) synthesis via activated phosphate/phosphonate substrates; (iii) Mitsunobu coupling between a nucleoside and methylenebisphosphonic acid; (iv) phosphorylation of a protected nucleoside under Yoshikawa's reaction conditions with methylenebis(phosphonic dichloride); (v) synthesis via nucleophilic cleavage of cyclic trimetaphosph(on)ates; (vi) enzyme-mediated reactions. [ABSTRACT FROM AUTHOR]

The emergence of infectious diseases caused by pathogenic bacteria is widespread. Therefore, it is urgently required to enhance the development of novel antimicrobial agents with high antibacterial activity and low cytotoxicity. A series of novel dialkyl cationic amphiphiles bearing two identical length lipophilic alkyl chains and one non-peptidic amide bond were synthesized and tested for antimicrobial activities against both Gram-positive and Gram-negative bacteria. Particular compounds synthesized showed excellent antibacterial activity toward drug-sensitive bacteria such as S. aureus , E. faecalis , E. coli and S. enterica , and clinical isolates of drug-resistant species such as methicillin-resistant S. aureus (MRSA), KPC-producing and NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE). For example, the MIC values of the best compound 4g ranged from 0.5 to 2 μg/mL against all these strains. Moreover, these small molecules acted rapidly as bactericidal agents, and functioned primarily by permeabilization and depolarization of bacterial membranes. Importantly, these compounds were difficult to induce bacterial resistance and can potentially combat drug-resistant bacteria. Thus, these compounds can be developed into a new class of antibacterial peptide mimics against Gram-positive and Gram-negative bacteria, including drug-resistant bacterial strains. [ABSTRACT FROM AUTHOR]

A chemical library comprised of nineteen synthesized pyridyl disulfides that emulate the chemical reactivity of allicin (garlic) was evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus (VISA, VRSA) demonstrated the highest level of susceptibility toward analogs with S -alkyl chains of 7–9 carbons in length. Further biological studies revealed that the disulfides display synergy with vancomycin against VRSA, cause dispersal of S. aureus biofilms, exhibit low cytotoxicity, and decelerate S. aureus metabolism. In final analysis, pyridyl disulfides represent a novel class of mechanism-based antibacterial agents that have a potential application as antibiotic adjuvants in combination therapy of S. aureus infections with reduced vancomycin susceptibility. [ABSTRACT FROM AUTHOR]

Aerolysin protein pore has been widely used for sensing peptides and proteins. However, only a few groups explored this nanopore for nucleic acids detection. The challenge is the extremely low capture efficiency for nucleic acids (>10 bases), which severely lowers the sensitivity of an aerolysin-based genetic biosensor. Here we reported a simple and easy-to-operate approach to noncovalently transform aerolysin into a highly nucleic acids-sensitive nanopore. Through a remote pH-modulation mechanism, we simply lower the pH on one side of the pore, then aerolysin is immediately "activated" and enabled to capture target DNA/RNA efficiently from the opposite side of the pore. This mechanism also decelerates DNA translocation, a desired property for sequencing and gene detection, allowing temporal separation of DNAs in different lengths. This method provides insight into the nanopore engineering for biosensing, making aerolysin applicable in genetic and epigenetic detections of long nucleic acids. [ABSTRACT FROM AUTHOR]

Rationale: The frequently used pesticide cyproconazole (Cyp) interacts with the essential elements commonly present in soil which play important roles in various enzymatic processes. These interactions predetermine the Cyp degradation pathways. We suggest a simple experimental and theoretical approach for the prediction of pesticide behavior. Methods: Cu/Cyp complexes are explored because of the typical Cu(II) reduction in complexes. Its level and the stability of the Cu-ligand bond depend on the type and the number of the surrounding ligands. Zn/Cyp complexes were compared as it is not expected that Zn(II) will reduce. The complexations were studied by means of electrospray ionization ion trap mass spectrometry and MS/MS collision-induced dissociations with comparative and explicative density functional theory calculations. Results: The Cyp ligand allows both Cu(II) reduction as well as, in specific cases, it protects the higher Cu oxidation state. The reduction is observed in the complexes with solely neutral Cyp where the number of ligands is below 3; a higher number protects the Cu(II) state. The metal atom binds to Cyp via N2 of the triazole ring as well as via π-electrons of the benzene ring; additional stabilization brings an interaction with the deprotonated OH group. Conclusions: The character of Cyp interactions with doubly charged metals (Cu(II), Zn(II)) clarified the creation of Cyp metabolites. The phenyl and triazole rings are bound to the metal cation and enable access for the isopropyl ring to be cleaved leaving the common metabolite (CAS Number: 58905-19-4). [ABSTRACT FROM AUTHOR]

The pine wood nematode Bursaphelenchus xylophilus has caused enormous economic losses in forests of many countries in the world. Many scientists have studied this disease, but the pathogenesis is still not fully understood. Our previous study showed that the thaumatin-like protein of B. xylophilus (Bx-TLP-1) was most similar to that of western white pine (TLP-S3: ADB97933.1 ) in structure and homology. To further explore the role of the thaumatin-like protein in the interaction of B. xylophilus with host pine, we cloned gene that encodes the thaumatin-like protein from Pinus massoniana , named Pm-tlp (gene accession number: KM063439 ). The deduced protein contains 180 amino acids, including 10 conserved cysteine residues. We also analyzed the expression of the two proteins from pine wood nematode and pine (roots, stems and needles) after inoculation with B. xylophilus . We found that over a month, the peaks of Bx-tlp-1 expression alternated with those of Pm-tlp . Furthermore, the first Bx-tlp-1 expression peak was earlier than Pm-tlp expression in stems and needles. In addition, we found that the α-pinene content corresponded with the expression of Bx-tlp-1 and Pm-tlp expression over the evaluated time course. The results showed that Bx-tlp-1 may interfere with the expression of Pm-tlp and the defense system to achieve its parasitism in the host, which may further influence the pinene content. These results provide information for further study of the function of thaumatin-like proteins in the interaction of B. xylophilus with P. massoniana. [ABSTRACT FROM AUTHOR]

A bimetallic metal-organic framework of the type MOF(Co/2Fe), synthesized by a hydrothermal method, is demonstrated to exhibit peroxidase-like activity and oxidase-like activity. The material catalyzes the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) to produce a blue product both in the absence and presence of HO. Its catalytic activity strongly depends on temperature and the solution pH value. With its dual enzyme mimetic activity, MOF(Co/2Fe) has the advantages of low cost, good stability, ease of preparation, and attractive Michaelis-Menten behavior. The mechanisms and kinetics of the pseudo-enzymatic activity were studied in some detail. A colorimetric method was developed for determination of HO that is based on the peroxidase-like activity of MOF(Co/2Fe). Under the optimal conditions, the absorbance of oxidized TMB at 652 nm increases linearly in the 10 to 100 μM HO concentration range, with a 5 μM limit of detection. [ABSTRACT FROM AUTHOR]

In the present paper we explore if interaction with a second person may change the experience and perception of the taste of distasteful beverages. The aim of the current research is to explore the impact of mimicry on flavor perception of unsought beverages which are beneficial, but due to factors such as unpleasant taste may be perceived negatively and thus avoided. In the first study, the participants were either mimicked or not mimicked by the confederate. The second study focused on measuring the amount of mimicry engaged in by the participant. The research reported here demonstrates that (1) mimicry of others can be used to influence their willingness to purchase an unsought product and to increase the price they are willing to pay for it, and (2) the level of non-conscious mimicry by a consumer can be used to predict their willingness to purchase an unsought product. [ABSTRACT FROM AUTHOR]

LiAlH4, LiAlMe4, or NaAlH4 react with commercially available HOSi R3, (-OSi R3 = -OSi tBuMe2, -OSiPh3) to afford [Li(THF)2][Al(OSi tBuMe2)4] ( 1), [Na(THF)2][Al(OSi tBuMe2)4] ( 2), and [Li(THF)4][Al(OSiPh3)4] ( 3). Ligand exchange reactions at the alkali metal ions in 1 and 3 with pyridine, 2,2′-bipyrimidine, and water yielded complexes [Li(py)2][Al(OSi tBuMe2)4] ( 4), [Al(OSi tBuMe2)4Li(H2O)]2(bpym) ( 5), and [Li(THF)(H2O)][Al(OSiPh3)4] ( 6). The X-ray crystal structures of complexes 1, 3, 4, 5, and 6 are presented. The complex [quinuclidineH][Al(OSi tBuMe2)4] ( 7), was produced via reaction of quinuclidine ·hydrochloride with 2. It features a hydrogen bonding interaction between an N-H group with a Si-O-Al unit, as proposed for the surfaces of zeolites after base treatment. [ABSTRACT FROM AUTHOR]

In this paper, the monosubstituted [Fe2(CO)5P(OMe)3{μ-(edt)}] ( 2) and the disubstituted [Fe2(CO)4(P(OMe)3)2{μ-(edt)}] ( 3) complexes we re-synthesized by CO substitution using thermal activation method. In contrast, Darchen and co-workers prepared complexes 2 and 3 by electron transfer catalysis method. The resulting complexes were characterized by different spectroscopic techniques. A detailed electrochemical study of complexes 2 and 3 in the absence and presence of the weak acetic acid, AcOH, was also reported. The structure of complexes 2 and 3 were confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Antifreeze proteins from polar fish species are remarkable biomacromolecules which prevent the growth of ice crystals. Ice crystal growth is a major problem in cell/tissue cryopreservation for transplantation, transfusion and basic biomedical research, as well as technological applications such as icing of aircraft wings. This review will introduce the rapidly emerging field of synthetic macromolecular (polymer) mimics of antifreeze proteins. Particular focus is placed on designing polymers which have no structural similarities to antifreeze proteins but reproduce the same macroscopic properties, potentially by different molecular-level mechanisms. The application of these polymers to the cryopreservation of donor cells is also introduced. [ABSTRACT FROM AUTHOR]

Distribution patterns/performance of magnetic nanoparticles (MNPs) was visualized by computer simulation and experimental validation on agarose gel tissue-mimicking phantom (AGTMP) models. The geometry of a complex three-dimensional mathematical phantom model of a cancer tumor was examined by tomography imaging. The capability of mathematical model to predict distribution patterns/performance in AGTMP model was captured. The temperature profile vs. hyperthermia duration was obtained by solving bio-heat equations for four different MNPs distribution patterns and correlated with cell death rate. The outcomes indicated that bio-heat model was able to predict temperature profile throughout the tissue model with a reasonable precision, to be applied for complex tissue geometries. The simulation results on the cancer tumor model shed light on the effectiveness of the studied parameters. [ABSTRACT FROM AUTHOR]

The peroxidase-like catalytic activity of MoS 2 nanomaterials has been utilized for colorimetric bioassays and medical diagnostics. However, the application of peroxidase-like catalytic activity of MoS 2 nanomaterials in environmental analysis was seldom explored. Herein, copper ions were found to inhibit the peroxidase-like catalytic activity of MoS 2 nanosheets, which can catalyze the oxidation of 3, 3′, 5, 5′-tetramethylbenzidine by H 2 O 2 to produce a colorimetric product. Based on this finding, a simple sensitive colorimetric method for the detection of copper ions was developed. In the presence of copper ions, the absorbance and color of the solution decreased with the increasing concentration of copper ions. The color of the solution can be used to semi-quantitative on-site assay of copper ions by naked eyes. A linear relationship between the absorbance and the concentration of copper ions was observed in the range of 0.4–4.0 μmol L − 1 with a detection limit of 92 nmol L − 1 , which was much lower than the maximum contaminant level of copper in drinking water legislated by the Environmental Protection Agency of USA and the World Health Organization. The method was applied to detect copper ions in environmental water samples with satisfactory results. [ABSTRACT FROM AUTHOR]

Glutathione peroxidase is key for the removal of H2O2 and other hydroperoxides and therefore, it has an important role in the maintenance of the reactive oxygen species (ROS) metabolic balance in vivo. The native enzymes of the glutathione peroxidase family (GPx) have many defects, such as instability in vitro and poor availability. GPx mimetics has become a topic of considerable interest in artificial enzyme research. Many forms of GPx mimics have been synthesized, by including selenium and tellurium (double-bridged and single-bridged, 2-substituted and 6-substituted) in a mother molecule but differences the GPx mimics enzymatic activity have rarely been compared. We designed and synthesized eight cyclodextrin derivatives and used two types of enzyme assays to determine their activities. The results show that: (a) tellurium-containing GPx mimics have higher activity than that of selenium-containing GPx mimics; (b) dual-bridged mimics have higher activity than bis-bridged mimics; and (c) 2-position modified cyclodextrin has higher activity than 6-position modified cyclodextrin. [ABSTRACT FROM AUTHOR]

In order to overcome the instability of natural glutathione peroxidase (GPx), scientists endeavor to produce GPx mimics. The popular method first uses biological imprinting (BI) to produce the substrate binding sites and then employs chemical mutation (CM) to obtain the catalytic site. However, BICM has a drawback in that the catalytic site is not clear. Some researchers therefore tried to change the order of the method. These new GPx mimics were prepared by first producing the catalytic site through chemical mutation, and then employing biological imprinting to produce the substrate binding sites (CMBI). It has a clear catalytic site, but its determination of enzyme activity and kinetic analysis are still not elucidated. In this study, we used CMBI to synthesize a GPx mimic using trypsin as the imprinted molecule and GSSG as the template molecule and compared the enzyme activity of the four intermediates (Trypsin-SeO2H (TSeO2H), Trypsin-Se-SG (TSeSG), Imprinted Trypsin-Se-SG (ITSeSG), Cross-linked Imprinted Trypsin-Se-SG (CITSeSG), we analyzed the properties of intermediate products. All values are the means of at least four determinations, ITSeSG was produced from TSeSG through bio-imprinting, the activity of GPx mimics synthesized by CMBI was 5.7 times greater than native GPx, because of bio-imprinting make KmGSH value of the mimics decreased from 4.82± 0.27 mM (TSeSG) to 0.52 ± 0.05 mM (ITSeSG). This proves that bio-imprinting is the reason for increased substrate binding capability. [ABSTRACT FROM AUTHOR]

Polyketide biosynthetic pathways have been engineered to generate natural product analogs for over two decades. However, manipulation of modular type I polyketide synthases (PKSs) to make unnatural metabolites commonly results in attenuated yields or entirely inactive pathways, and the mechanistic basis for compromised production is rarely elucidated since rate-limiting or inactive domain(s) remain unidentified. Accordingly, we synthesized and assayed a series of modified pikromycin (Pik) pentaketides that mimic early pathway engineering to probe the substrate tolerance of the PikAIII-TE module in vitro. Truncated pentaketides were processed with varying efficiencies to corresponding macrolactones, while pentaketides with epimerized chiral centers were poorly processed by PikAIII-TE and failed to generate 12-membered ring products. Isolation and identification of extended but prematurely offloaded shunt products suggested that the Pik thioesterase (TE) domain has limited substrate flexibility and functions as a gatekeeper in the processing of unnatural substrates. Synthesis of an analogous hexaketide with an epimerized nucleophilic hydroxyl group allowed for direct evaluation of the substrate stereoselectivity of the excised TE domain. The epimerized hexaketide failed to undergo cyclization and was exclusively hydrolyzed, confirming the TE domain as a key catalytic bottleneck. In an accompanying paper, we engineer the standalone Pik thioesterase to yield a thioesterase (TES148C) and module (PikAIII-TES148C) that display gain-of-function processing of substrates with inverted hydroxyl groups. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing technologies enable rapid laboratory-scale customization of experimental devices to fit the user’s requirements. To demonstrate how 3D-printed objects can be functionalized through incorporation of reactive substances into the raw materials prior to printing, this paper describes a multi-well plate fabricated using polylactic acid (PLA) filaments that had been treated in advance with iron oxide (Fe 2 O 3 , Fe 3 O 4 ) nanoparticles that possess intrinsic peroxidase activities. The fabricated multi-well plate efficiently catalyzed the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by the peroxidase substrate hydrogen peroxide and allowed measurements of the resulting absorbance through direct loading of the plate into a plate reader. The applicability of this 3D-printed peroxidase mimic–incorporating multi-well plate has been examined in terms of the device’s reusability and analytical performance, analyses of reaction kinetics, and the high-throughput determination of glucose concentrations in clinical and food samples. The results suggest that this functionalization scheme can diversify the utility of current 3D printing technologies in the fabrication of experimental devices with properties comparable with or superior to those of conventional systems. [ABSTRACT FROM AUTHOR]

The biotrophic pathogen Xanthomonas oryzae pv. oryzae ( Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides., Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides., Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence., These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. [ABSTRACT FROM AUTHOR]

Xenoestrogens (XEs) mimic or block the synthesis, metabolism and transport of normal endogenous hormones, disturbing normal endocrine function. The available data on the nonmonotonic estrogenic effects of low doses of many XEs are reviewed, covering in vitro , in vivo and epidemiological studies. The observed nonmonotonic patterns of the dose-response curves are discussed, along with possible underlying mechanisms. This review is intended to provide guidance for harm predication and to suggest prevention measures. [ABSTRACT FROM AUTHOR]

The enigmatical dichotomy between the two CERT/GPBP protein isoforms, their vast panel of biological implications and the scarcity of known antagonist series call for new ligand chemotypes identification. We report the design of iminosugar-based ceramide mimics for the development of new START domain ligands potentially targeting either protein isoforms. Strategic choice of (i) an iminoxylitol core structure and (ii) the positioning of two dodecyl residues led to an extent of protein binding comparable to that of the natural cargo lipid ceramide or the archetypical inhibitor HPA-12. Molecular docking study evidenced a possible mode of protein binding fully coherent with the one observed in crystalline co-structures of known ligands. The present study thus paves the way for cellular CERT inhibition studies en route to the development of pharmacological tools aiming at deciphering the respective function and therapeutic potential of the two CERT/GPBP protein isoforms. [ABSTRACT FROM AUTHOR]

Selection methods are used to identify Affimers that recognise α-helix mimicking N-alkylated aromatic oligoamides thus demonstrating foldamer and natural α-amino acid codes are compatible. [ABSTRACT FROM AUTHOR]

P-glycoprotein (Pgp) is a membrane bound efflux pump spread in a variety of tumor cells and considered as a main component of multidrug resistance (MDR) to chemotherapies. In this work, three groups of compounds (imidazolone, oxazolone and vinyl dipeptide derivatives) were synthesized aiming to develop a molecular framework that effectively suppresses MDR. When tested for their influence on Pgp activity, four compounds coded Cur1-01, Cur1-12V, Curox-1 and Curox-3 significantly decreased remaining ATP concentration indicating Pgp substrate site blocking. On the other hand, Cur-3 and Cur-10 significantly increased remaining ATP concentration, which is indicative of Pgp ATPase inhibition. The cytotoxicity of synthesized compounds was examined against Pgp expressing/highly resistant colorectal cancer cell lines (LS-174T). Compounds Cur-1 and Cur-3 showed considerable cytotoxicity with IC50 values of 7.6 and 8.9 μM, respectively. Equitoxic combination (at IC50 concentrations) of PTX and Cur-3 greatly diminished resistant cell clone from 45.7% to 2.5%, albeit with some drop in potency from IC50 of 7.9 nM to IC50 of 23.8 nM. On the other hand, combination of PTX and the non-cytotoxic Cur1-12V (10 μM) significantly decreased the IC50 of PTX to 3.8 nM as well as the resistant fraction to 16.2%. The combination test was confirmed using the same protocol but on another resistant CRC cell line (HCT-116) as we obtained similar results. Both Cur-3 and Cur1-12V (10 μM) significantly increased the cellular entrapment of Pgp probe (doxorubicin) elevating its intracellular concentration from 1.9 pmole/cell to 3.0 and 2.9 pmole/cell, respectively. [ABSTRACT FROM AUTHOR]

Autoimmune disorders are formed in the body as an outcome of inappropriate immune response against its own tissues. Failure of this immune system to recognize the body's normal constituents as "self" will result in inflammation and tissue damage. Several immune based mechanisms form the basis of autoimmune disorders in the body. Management of these lesions is based on the diagnostic criteria, evaluation of clinical and oral manifestation, and laboratory investigations of these lesions. There is currently no definitive cure for all autoimmune disorders, although in rare cases they may disappear on their own. As patients experience temporary remissions in symptoms or progressive worsening, our pharmacological management are targeted only for symptomatic relief and arrest the progression of the lesion. A detailed approach to titles and abstracts of importance in this field on the topic of interest via review and case reports was included. This review article highlights on various immune pathogenic mechanisms and treatment modalities of autoimmune disorders. [ABSTRACT FROM AUTHOR]

Two-electron reduction of the TiIV compound (ketguan)(ImDippN)Ti(OTf)2 ( 3) gives the arene-masked complex (ketguan)(η6-ImDippN)Ti ( 1) in excellent yield. Upon standing in solution, 1 converts to a TiIV metallacycle ( 4) through dehydrogenation of a pendant isopropyl group. Spectroscopic evidence shows this transformation initially proceeds via the oxidative addition of a C(sp3)−H bond and can be reversed upon exposure of 4 to H2. Interestingly, treatment of 1 with cyclohexene gives cyclohexane and 4 via a titanium-mediated transfer hydrogenation reaction, a process that can be extended to catalytically hydrogenate other unsaturated hydrocarbons under mild conditions. These results, rare for the early-metals, suggest 1 possesses chemical characteristics reminiscent of noble, late-metals. [ABSTRACT FROM AUTHOR]

Nerve Growth Factor (NGF) is one of the members of the neurotrophin family with multifaceted functions. However, clinical application of NGF is hurdled by the challenge on formulation development. The objective of this study was to develop novel high-density lipoproteins (HDL)-mimicking nanoparticles (NPs) coated with α-tocopherol to incorporate NGF by a self-assembly approach. The NPs were prepared by an optimized self-assembly method that is simple and scalable. The composition of HDL-mimicking NPs was optimized. The prototype of the HDL-mimicking α-tocopherol-coated NPs contained phosphatidylserine (a negative charged phospholipid) and d -α-Tocopheryl polyethylene glycol succinate (a source of vitamin E) to enhance the entrapment efficiency of apolipoprotein A-I in the NPs. The entrapment efficiency of apolipoprotein A-I was about 30%. The NPs had particle size about 200 nm with a relatively narrow size distribution. Finally, cationic ion-pair agents were optimized to form ion-pairs with NGF to facilitate the incorporation of NGF into the NPs. Protamine sodium salt USP formed an optimal ion-pair complex with NGF. The results showed that the novel HDL-mimicking α-tocopherol-coated NPs successfully encapsulated NGF with over 65% entrapment efficiency by using this ion-pair strategy. In vitro release studies demonstrated a slow release of NGF from NGF NPs in PBS containing 5% BSA at 37 °C for 72 h. Further biodistribution studies showed that intravenously injected NGF NPs significantly increased NGF concentration in plasma and decreased the uptake in liver, spleen and kidney, compared to free NGF in mice. [ABSTRACT FROM AUTHOR]

Literature sources on metal-organic materials encapsulating versatile porphyrinoids and heme enzymes have been discussed in this review. General fundamentals and structural and chemical requisites of these architectures are discussed in introduction followed by historical perspectives of the initial composites. We have categorized the structural aspects of this class of compounds according to the host and guest skeletons as well as encapsulating strategies in a sequential manner. Heme mimetic, as well as some novel applications of the materials including oxidation, electron transfer, carbene transfer and bio-molecule sensing, are then discussed and compared with each other and their homogeneous analogues based on mechanistic similarities, wherever possible. [ABSTRACT FROM AUTHOR]

Gentisate-1,2-dioxygenase (GDO), a nonheme iron enzyme in the cupin superfamily, catalyzes the cleavage of the aromatic-ring of 2,5-dihydroxybenzoic acid (gentisic acid) to form maleylpyruvic acid in the microbial aerobic degradation of aromatic compounds. To develop a functional model of GDO, we have isolated a nonheme iron(II) complex, [(TpPh2)FeII(DHN-H)] (TpPh2=hydrotris(3,5-diphenylpyrazole-1-yl)borate, DHN-H=1,4-dihydroxy-2-naphthoate). In the reaction with O2, the biomimetic complex oxidatively cleaves the aromatic ring of the coordinated substrate with the incorporation of both the oxygen atoms from molecular oxygen into the cleavage product. The presence of para-hydroxy group on the substrate plays a crucial role in directing the aromatic-ring cleaving reaction. [ABSTRACT FROM AUTHOR]

In mammals, the non-heme iron enzyme cysteine dioxygenase (CDO) helps regulate Cys levels through converting Cys to Cys sulfinic acid. Its activity is in part modulated by the formation of a Cys93–Tyr157 crosslink that increases its catalytic efficiency over 10-fold. Here, 21 high-resolution mammalian CDO structures are used to gain insight into how the Cys–Tyr crosslink promotes activity and how select competitive inhibitors bind. Crystal structures of crosslink-deficient C93A and Y157F variants reveal similar ~ 1.0-Å shifts in the side chain of residue 157, and both variant structures have a new chloride ion coordinating the active site iron. Cys binding is also different from wild-type CDO, and no Cys-persulfenate forms in the C93A or Y157F active sites at pH 6.2 or 8.0. We conclude that the crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry. In addition, structures are presented for homocysteine (Hcy), D-Cys, thiosulfate, and azide bound as competitive inhibitors. The observed binding modes of Hcy and D-Cys clarify why they are not substrates, and the binding of azide shows that in contrast to what has been proposed, it does not bind in these crystals as a superoxide mimic. [ABSTRACT FROM AUTHOR]

Recently, we reported a directed evolution method which enabled us to discover sequences of glycopeptides that bind with picomolar affinity to HIV antibody 2G12 and are of interest as HIV vaccine candidates. In this manuscript, we describe the syntheses of several of these large (∼11–12 kDa) glycopeptides by a combination of fast flow peptide synthesis and click chemistry. We also discuss the optimization of their attachment to carrier protein CRM197, affording antigenic and immunogenic conjugates ready for animal vaccination. [ABSTRACT FROM AUTHOR]

During the past year, many articles were published on the extragastric diseases related to Helicobacter pylori infection. This supports the theory that some microorganisms may cause diseases even far from the primary site of infection by interfering with different biologic processes. The role of H. pylori on idiopathic thrombocytopenic purpura, sideropenica anemia, and vitamin B12 deficiency is well known. On the other hand, there is a growing interest in the bacterium's association with cardiovascular, neurologic, hematologic, dermatologic, head and neck, and uro-gynecologic diseases, as well as diabetes mellitus and metabolic syndrome, with very promising results. This review has been aimed at summarizing the results of the most relevant studies published over the last year on this fascinating topic. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the movement of molecules in crowded environments with obstacles undergoing Brownian motion by means of extensive Monte Carlo simulations. Our investigations were performed using the dynamic lattice liquid model, which was based on the cooperative movement concept and allowed to mimic systems at high densities where the motion of all elements (obstacles as well as moving particles) were highly correlated. The crowded environments are modeled on a two-dimensional triangular lattice containing obstacles (particles whose mobility was significantly reduced) moving by a Brownian motion. The subdiffusive motion of both elements in the system was analyzed. It was shown that the percolation transition does not exist in such systems in spite of the cooperative character of the particles' motion. The reduction of the obstacle mobility leads to the longer caging of liquid particles by mobile obstacles. [ABSTRACT FROM AUTHOR]

The difluoromethyl phosphonate motif plays a crucial role in the development of bioactive molecules as it is considered as a phosphate bioisoster. Since 2010, a renewal of interest to enlarge the panel of reactions to access these difluoromethylated phosphonate-containing molecules has been witnessed. This Concept article charts the recent progress that has been made. [ABSTRACT FROM AUTHOR]

Interleukin 6 plays a key role in mediating inflammatory reactions in autoimmune diseases and cancer, where it is also involved in metastasis and tissue invasion. Neutralizing antibodies against IL-6 and its receptor have been approved for therapeutic intervention or are in advanced stages of clinical development. Here we describe the crystal structures of the complexes of IL-6 with two Fabs derived from conventional camelid antibodies that antagonize the interaction between the cytokine and its receptor. The x-ray structures of these complexes provide insights into the mechanism of neutralization by the two antibodies and explain the very high potency of one of the antibodies. It effectively competes for binding to the cytokine with IL-6 receptor (IL-6R) by using side chains of two CDR residues filling the site I cavities of IL-6, thus mimicking the interactions of Phe229 and Phe279 of IL-6R. In the first antibody, a HCDR3 tryptophan binds similarly to hot spot residue Phe279. Mutation of this HCDR3 Trp residue into any other residue except Tyr or Phe significantly weakens binding of the antibody to IL-6, as was also observed for IL-6R mutants of Phe279. In the second antibody, the side chain of HCDR3 valine ties into site I like IL-6R Phe279, whereas aLCDR1tyrosine side chain occupies a second cavity within site I and mimics the interactions of IL-6R Phe229. [ABSTRACT FROM AUTHOR]