Inaccurate chemical structures of dyes and fluorochromes found in the literature can be problematic for teaching and research

Abstract

Representations of the chemical structures of dyes and fluorochromes often are used to illustrate staining mechanisms and histochemical reactions. Unfortunately, inaccurate chemical structures sometimes are used, which results in problems for teaching and research in histochemistry. We comment here on published examples of inadequate chemical drawing and modeling. In particular, omission of hydrogen atoms can lead to misleading hydrogen-bonding interactions, and inaccurate drawing and modeling procedures result in a variety of implausible molecular structures. The examples and arguments given here are easily intelligible for non-chemists and could be used as part of a training approach to help avoid publication of misleading or puzzling dye structures and molecular models for illustrating biological staining and histochemical studies.     

Pseudogene

Abstract

The article describes organic photochemical reactions in heterogeneous fields. The first part of the article includes an introduction of miscellaneous electrostatic fields adsorbing photoactive species and the second part summarizes the types of photochemical reactions in their fields. Photochemical reactions carried out in various heterogeneous fields, inorganic as well as organic, were classified by their reaction type, that is, unimolecular reactions, bimolecular reactions, energy transfer reactions, and electron transfer reactions.     

Physical,chemical and biological characteristics* of CO2 gas flux across the air-water interface

Abstract Carbon dioxide gas flux across the air-water interface is most often treated as a ‘simple’ physical process, primarily responding to wind speed and water temperature. Available experimental data yield an exponential regression equation relating wind speed to the thickness of a stagnant boundary film through which gas diffuses to or from the water. Flux of CO₂ is influenced by CO₂ hydration reactions in the stagnant boundary layer. High pH and a thick stagnant boundary layer favour chemical enhancement of the CO₂ gas flux. The rate of CO₂ flux reflects the sum of net organic metabolism plus CaCO₃ reactions. Some interesting gas-flux constraints on the rate of net organic carbon production and on global geochemical cycling of CaCO₃ emerge. At high pH (circa 10), the maximum net organic carbon production which can be supported by CO₂ flux across the air-water interface is about 0.06 mol C m^&2 d^&1. On a global scale, organic C, not atmospheric C, appears to account for the ‘CO₂’ term in the classical CaCO₃ dissolution-precipitation reaction.     

Production of the PET isotope 11C in hadron therapy via neutron knockout

PurposePositron emitting isotopes such as ¹¹C and ¹⁰C can be used for vital dose verification in hadron therapy. These isotopes are produced when the high energy ¹²C primary beam particles undergo nuclear reactions within the patient.MethodsWe discuss a model for calculating cross sections for the production ¹¹C in ¹²C + ¹²C collisions, applicable at hadron therapy energies.ResultsGood agreement with the available cross section measurements is found for ¹²C(−1n), though more detailed, systematic measurements would be very valuable.ConclusionsNuclear structure plays a crucial role in the reactions of light nuclei, particularly when those reactions are peripheral and involve only a few nucleons. For such reactions, nuclear structure has a strong influence on the energy and angular distribution of the cross section, and is an important consideration for reliable dose verification using ¹¹C in hadron therapy.     

Hematoxylin and related compounds – an annotated bibliography concerning their origin,properties, chemistry,and certain applications

Abstract

This bibliography covers the historical aspects of hematoxylin and its close relative brazilin from their origin in dyewoods to their recently understood chemical reactions and properties. Until the end of the 19th century, dyewoods such as logwood were among the most commercially important natural dyes and investigations over a long period of time led to an extensive literature. The ready oxidation of hematoxylin to hematein, which subsequently can be complexed with metal ions or undergo reactions with acid to give isohematein, has provided a wealth of work for the organic chemist. The elucidation of the structure and subsequent synthesis of hematoxylin has proved to be a major incentive to chemists to discover novel chemical reagents for many years.     

Preliminary results in using Deep Learning to emulate BLOB,a nuclear interaction model

PurposeA reliable model to simulate nuclear interactions is fundamental for Ion-therapy. We already showed how BLOB (“Boltzmann-Langevin One Body”), a model developed to simulate heavy ion interactions up to few hundreds of MeV/u, could simulate also ¹²C reactions in the same energy domain. However, its computation time is too long for any medical application. For this reason we present the possibility of emulating it with a Deep Learning algorithm.MethodsThe BLOB final state is a Probability Density Function (PDF) of finding a nucleon in a position of the phase space. We discretised this PDF and trained a Variational Auto-Encoder (VAE) to reproduce such a discrete PDF. As a proof of concept, we developed and trained a VAE to emulate BLOB in simulating the interactions of ¹²C with ¹²C at 62 MeV/u. To have more control on the generation, we forced the VAE latent space to be organised with respect to the impact parameter (b) training a classifier of b jointly with the VAE.ResultsThe distributions obtained from the VAE are similar to the input ones and the computation time needed to use the VAE as a generator is negligible.ConclusionsWe show that it is possible to use a Deep Learning approach to emulate a model developed to simulate nuclear reactions in the energy range of interest for Ion-therapy. We foresee the implementation of the generation part in C++ and to interface it with the most used Monte Carlo toolkit: Geant4.     

On the Emergence of Biological Complexity: Life as a Kinetic State of Matter

A kinetic model that attempts to further clarify the nature of biological complexification is presented. Its essence: reactions of replicating systems and those of regular chemical systems follow different selection rules leading to different patterns of chemical behavior. For regular chemical systems selection is fundamentally thermodynamic, whereas for replicating chemical systems selection is effectively kinetic. Building on an extension of the kinetic stability concept it is shown that complex replicators tend to be kinetically more stable than simple ones, leading to an on-going process of kinetically-directed complexification. The high kinetic stability of simple replicating assemblies such as phages, compared to the low kinetic stability of the assembly components, illustrates the complexification principle. The analysis suggests that living systems constitute a kinetic state of matter, as opposed to the traditional thermodynamic states that dominate the inanimate world, and reaffirms our view that life is a particular manifestation of replicative chemistry.     

Efficient Test Molecule Sampling in Molecular Simulation

Abstract

Excluded volume map sampling (EVMS) is a particularly efficient means of performing test molecule sampling to estimate or impose chemical potential in molecular simulations. This paper discusses the motivation and applications of excluded volume map sampling, presents computer code demonstrating its implementation, and gives an example of its application.     

Microbially Influenced Corrosion as a Model System for the Study of Metal Microbe Interactions: A Unifying Electron Transfer Hypothesis

The general term biomineralisation refers to biologically induced mineralisation in which an organism modifies its local microenvironment creating conditions such that there is chemical precipitation of mineral phases extracellularly. Most usually this results from an oxidation or reduction carried out by some microbial species, with the formation of a recognised biomineralised product. These reactions play a major role in microbial physiology and ecology, and are of central importance to such engineering consequences as microbial mining and microbially influenced corrosion. This paper will examine metal microbe interactions, both in naturally occurring microbial ecosystems and in two particular cases of biocorrosion, with the objective of putting forward a unifying hypothesis relevant to the understanding of each of these apparently disparate processes.     

Enhanced sampling of chemical and biochemical reactions with metadynamics

Metadynamics (MetaD) is a method that augments molecular dynamics (MD) calculations of all types (classical and quantum) to help systems overcome energy barriers and explore regions of phase space that would otherwise not be seen during a simulation. The method has seen wide ranging uses, and it has proven especially useful for the study of reactions in which bonds break and form. In such cases, the timescale challenges of MD are profoundly limiting, and the advent of this new paradigm for biasing simulations has proven to be incredibly useful. In this review, we set out to summarise the large body of work that uses MetaD for studying reactions so that others can more easily implement this method in their own work. After a brief introduction of the method, we provide detailed summaries of the method applied in various contexts including condensed phase and biological reactions.     

Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan

BackgroundThe extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration.Scope of reviewHere, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury.Major conclusionsThe brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis.General significanceGenetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury.This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa.     

Rapid Routes of Synthesis of Oligonucleotide Conjugates from Non-Protected Oligonucleotides and Ligands Possessing Different Nucleophilic or Electrophilic Functional Groups

Abstract

Optimized methods are described for post-synthetic conjugation of non-protected oligodeoxyribonucleotides to different ligands. Methods for the terminal functionalization of oligonucleotides by amino, sulfhydryl, thiophosphate or carboxyl groups using different chemical reactions and linkers in both organic and aqueous media are described and compared. Experimental conditions for subsequent coupling of ligands containing aliphatic and aromatic amines, aromatic alcohols, carboxylic, sulfiydryl, alkylating, aldehydic and other reactive nucleophilic and electrophilic groups to oligonucleotides were established, including covalent linkage to other oligonucleotides.     

Isolation of Three Novel Rat and Mouse Papillomaviruses and Their Genomic Characterization

Despite a growing knowledge about the biological diversity of papillomaviruses (PV), only little is known about non-human PV in general and about PV mice models in particular. We cloned and sequenced the complete genomes of two novel PV types from the Norway rat (Rattus norvegicus; RnPV2) and the wood mouse (Apodemus sylvaticus; AsPV1) as well as a novel variant of the recently described MmuPV1 (originally designated as MusPV) from a house mouse (Mus musculus; MmuPV1 variant). In addition, we conducted phylogenetic analyses using a systematically representative set of 79 PV types, including the novel sequences. As inferred from concatenated amino acid sequences of six proteins, MmuPV1 variant and AsPV1 nested within the Beta+Xi-PV super taxon as members of the Pi-PV. RnPV2 is a member of the Iota-PV that has a distant phylogenetic position from Pi-PV. The phylogenetic results support a complex scenario of PV diversification driven by different evolutionary forces including co-divergence with hosts and adaptive radiations to new environments. PV types particularly isolated from mice and rats are the basis for new animal models, which are valuable to study PV induced tumors and new treatment options.     

Performance of cross-linked enzyme crystals of engineered halohydrin dehalogenase HheG in different chemical reactor systems

Halohydrin dehalogenase HheG is an industrially interesting biocatalyst for the preparation of different β-substituted alcohols starting from bulky internal epoxides. We previously demonstrated that the immobilization of different HheG variants in the form of cross-linked enzyme crystals (CLECs) yielded stable and reusable enzyme immobilizes with increased resistance regarding temperature, pH, and the presence of organic solvents. Now, to further establish their preparative applicability, HheG D114C CLECs cross-linked with bis-maleimidoethane have been successfully produced on a larger scale using a stirred crystallization approach, and their application in different chemical reactor types (stirred tank reactor, fluidized bed reactor, and packed bed reactor) was systematically studied and compared for the ring opening of cyclohexene oxide with azide. This revealed the highest obtained space-time yield of 23.9 kg_product g_CLEC⁻¹ h⁻¹ L_{reactor volume}⁻¹ along with the highest achieved product enantiomeric excess [64%] for application in a packed-bed reactor. Additionally, lyophilization of those CLECs yielded a storage-stable HheG preparation that still retained 67% of initial activity (after lyophilization) after 6 months of storage at room temperature.     

Evaluation of droplet-based microfluidic platforms as a convenient tool for lipases and esterases assays

Abstract

The accurate estimation of kinetic parameters is of fundamental importance for biochemical studies for research and industry. In this paper, we demonstrate the application of a modular microfluidic system for execution of enzyme assays that allow determining the kinetic parameters of the enzymatic reactions such as V_max – the maximum rate of reaction and K_M – the Michaelis constant. For experiments, the fluorogenic carbonate as a probe for a rapid determination of the kinetic parameters of hydrolases, such as lipases and esterases, was used. The microfluidic system together with the method described yields the kinetic constants calculated from the concentration of enzymatic product changes via a Michaelis–Menten model using the Lambert function W(x). This modular microfluidic system was validated on three selected enzymes (hydrolases).     

Ultrafiltration,a useful method for isolation of intermediates in native chemical ligation exemplified with the total synthesis of Sortase AΔN59

In this paper, ultrafiltration was employed to facilitate the isolation of intermediates in native chemical ligation. Depending on the molecular weight cutoff of the membrane used, molecules with different sizes could be purified, separated, or concentrated by the ultrafiltration process. Total chemical synthesis of the polypeptide chain of the enzyme Sortase A_ΔN59 was used as an example of the application of ultrafiltration in chemical protein synthesis. Sortase A is a ligase that catalyzes transpeptidation reactions between proteins that have C‐terminal LPXTG recognition sequence and Gly5‐ on the peptidoglycan of bacterial cell walls [3]. Ultrafiltration technique facilitated synthesis of Sortase A_ΔN59 and was a promising tool in isolation of intermediates in native chemical ligation. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Understanding the effect of adsorption on activated processes using molecular theory and simulation

Most chemical reactions of practical interest are catalysed by porous materials, which can improve reaction rates and equilibrium yields through various interactions with the reacting mixture. Nucleation, another kind of activated process, can also be substantially affected by the presence of a surface or by the confinement within a porous material. There are several different effects that can influence such activated processes, such as the reduced dimensionality of the porous space or the adsorbed layer, physical or chemical interactions with the adsorbate and transport limitations. This paper presents a unifying perspective on the influence of each of these effects on chemical reactions and crystallisation processes through the discussion of selected examples from the literature. The common aspects and the differences between these two different kinds of activated processes are considered in the context of each effect. Finally, some of the important issues that could benefit from the development of new molecular simulations methods are discussed.     

Assays of ceruloplasmin vs myeloperoxidase: Witnessing the great battle,or mixing chalk and cheese?

A paper in this issue [Panasenko et al., Biophysics 53 (4), 268 (2008)] furthers the idea of myeloperoxidase inhibition by ceruloplasmin, confirming the earlier reports with standard chlorination and peroxidase tests, and introducing a new version of the luminol chemiluminescence assay. However, there are outstanding discrepancies in the data on ceruloplasmin efficacy and their interpretation. In my opinion, they can be resolved only admitting that the supposedly equivalent assays register essentially different types of process, which involve the same chemical entities but on different spatiotemporal scales. The immediate flash caused by hydrogen peroxide in the myeloperoxidase/luminol/chloride mixture must reflect the non-equilibrium events within and/or at the surface of the enzyme molecule pre-loaded with the reactants. This phenomenon (which should perhaps be called “prompt chemiluminescence” in contrast to the much longer glow recorded in all usual assays and associated with secondary reactions in the bulk) is quite interesting in the biophysical aspect. It can be used for functional dissection of such multipathway, multilevel systems, and in particular, can indeed help clarify the situation concerning the putative ceruloplasmin control over myeloperoxidase. The article is published in original.     

Winter Stephanodiscus bloom development in the Nakdong River regulated by an estuary dam and tributaries

Planktonic organisms exhibit diverse morphological, behavioural and life-history responses to the chemical presence of potential predators. Prey organisms have been found to sense such predators via predator-derived kairomones. The induced reactions are assumed to reduce predation risk and thus to be adaptive. Numerous studies have investigated various aspects of inducible defences in different crustaceans, in rotifers, planktonic ciliates and algae. As a first step, we summarise recent work on chemically induced anti-predator defences in morphology, life history and behaviour. Morphological defences have been found in a wide range of different plankton organisms and recent studies on predator-induced morphologies mainly addressed the question of costs for these changes. Life-history responses were mainly studied in cladocerans and several studies have recently addressed some novel topics, such as diapause induction and the influence of predator kairomones on hatching of resting stages. Behavioural anti-predator defences also have been found for several plankton species and are characterised by relatively fast induction times. We further identified four research directions in which substantial progress has been made recently: (I) The effects of simultaneous exposure to infochemicals from different predators and the consequences of a complex chemical environment. Some environmental contaminants, such as synthetic chemicals or heavy metals, have been found to potentially disturb natural chemical communication in aquatic predator-prey systems. (II) The influence of genetic variation on the reaction to infochemicals and its implications. Clonal differences have not only been found for the presence or absence of a certain trait but also with respect to the type of response. (III) The degree to which different types of responses to a specific kairomone are coupled. Recent studies underline the uncoupling of different anti-predator responses of which some have been considered to be coupled. (IV) Studies on the chemical properties and on the metabolic origin of predator kairomones. Substantial progress has been made recently, especially with respect to the identification of predator kairomones that are important for planktonic ciliates. The identification and isolation of kairomones are an important step towards studies addressing the consequences of predator-induced defences on the level of populations, communities and ecosystems. So far most studies have considered effects and consequences on the level of individual prey organisms and studies taking the consequences at higher ecological levels into account are rare.