Halogenation in Fungi: What Do We Know and What Remains to Be Discovered?

In nature, living organisms produce a wide variety of specialized metabolites to perform many biological functions. Among these specialized metabolites, some carry halogen atoms on their structure, which can modify their chemical characteristics. Research into this type of molecule has focused on how organisms incorporate these atoms into specialized metabolites. Several families of enzymes have been described gathering metalloenzymes, flavoproteins, or S-adenosyl-L-methionine (SAM) enzymes that can incorporate these atoms into different types of chemical structures. However, even though the first halogenation enzyme was discovered in a fungus, this clade is still lagging behind other clades such as bacteria, where many enzymes have been discovered. This review will therefore focus on all halogenation enzymes that have been described in fungi and their associated metabolites by searching for proteins available in databases, but also by using all the available fungal genomes. In the second part of the review, the chemical diversity of halogenated molecules found in fungi will be discussed. This will allow the highlighting of halogenation mechanisms that are still unknown today, therefore, highlighting potentially new unknown halogenation enzymes.     

The GABAergic System and Endocannabinoids in Epilepsy and Seizures: What Can We Expect from Plant Oils?

Seizures and epilepsy are some of the most common serious neurological disorders, with approximately 80% of patients living in developing/underdeveloped countries. However, about one in three patients do not respond to currently available pharmacological treatments, indicating the need for research into new anticonvulsant drugs (ACDs). The GABAergic system is the main inhibitory system of the brain and has a central role in seizures and the screening of new ACD candidates. It has been demonstrated that the action of agents on endocannabinoid receptors modulates the balance between excitatory and inhibitory neurotransmitters; however, studies on the anticonvulsant properties of endocannabinoids from plant oils are relatively scarce. The Amazon region is an important source of plant oils that can be used for the synthesis of new fatty acid amides, which are compounds analogous to endocannabinoids. The synthesis of such compounds represents an important approach for the development of new anticonvulsant therapies.     

Thermal Plasma Technology: Where Do We Stand and Where Are We Going?

In this overview, an attempt is made to assess the present and future research and development in thermal plasma processing of materials restricted to (1) thermal plasma coating technologies, (2) thermal plasma synthesis of fine powders, (3) thermal plasma waste destruction, and (4) thermal plasma spheroidization and densification. Since thermal plasma processing is, in general, governed by a large number of parameters, implementation of controls becomes mandatory. The lack of sufficient controls combined with economic drawbacks in some cases has been the main obstacle for the growth of thermal plasma technology. Present R&D efforts, however, address these problems.     

Updates on Dengue Vaccine and Antiviral: Where Are We Heading?

Approximately 100–400 million people from more than 100 countries in the tropical and subtropical world are affected by dengue infections. Recent scientific breakthroughs have brought new insights into novel strategies for the production of dengue antivirals and vaccines. The search for specific dengue inhibitors is expanding, and the mechanisms for evaluating the efficacy of novel drugs are currently established, allowing for expedited translation into human trials. Furthermore, in the aftermath of the only FDA-approved vaccine, Dengvaxia, a safer and more effective dengue vaccine candidate is making its way through the clinical trials. Until an effective antiviral therapy and licensed vaccine are available, disease monitoring and vector population control will be the mainstays of dengue prevention. In this article, we highlighted recent advances made in the perspectives of efforts made recently, in dengue vaccine development and dengue antiviral drug.     

Cross‐Linking/Mass Spectrometry for Studying Protein Structures and Protein–Protein Interactions: Where Are We Now and Where Should We Go from Here?

Structural mass spectrometry (MS) is gaining increasing importance for deriving valuable three‐dimensional structural information on proteins and protein complexes, and it complements existing techniques, such as NMR spectroscopy and X‐ray crystallography. Structural MS unites different MS‐based techniques, such as hydrogen/deuterium exchange, native MS, ion‐mobility MS, protein footprinting, and chemical cross‐linking/MS, and it allows fundamental questions in structural biology to be addressed. In this Minireview, I will focus on the cross‐linking/MS strategy. This method not only delivers tertiary structural information on proteins, but is also increasingly being used to decipher protein interaction networks, both in vitro and in vivo. Cross‐linking/MS is currently one of the most promising MS‐based approaches to derive structural information on very large and transient protein assemblies and intrinsically disordered proteins.     

Distance-of-Flight Mass Spectrometry: What,Why, and How?

Distance-of-flight mass spectrometry (DOFMS) separates ions of different mass-to-charge (m/z) by the distance they travel in a given time after acceleration. Like time-of-flight mass spectrometry (TOFMS), separation and mass assignment are based on ion velocity. However, DOFMS is not a variant of TOFMS; different methods of ion focusing and detection are used. In DOFMS, ions are driven orthogonally, at the detection time, onto an array of detectors parallel to the flight path. Through the independent detection of each m/z, DOFMS can provide both wider dynamic range and increased throughput for m/z of interest compared with conventional TOFMS. The iso-mass focusing and detection of ions is achieved by constant-momentum acceleration (CMA) and a linear-field ion mirror. Improved energy focus (including turn-around) is achieved in DOFMS, but the initial spatial dispersion of ions remains unchanged upon detection. Therefore, the point-source nature of surface ionization techniques could put them at an advantage for DOFMS. To date, three types of position-sensitive detectors have been used for DOFMS: a microchannel plate with a phosphorescent screen, a focal plane camera, and an IonCCD array; advances in detector technology will likely improve DOFMS figures-of-merit. In addition, the combination of CMA with TOF detection has provided improved resolution and duty factor over a narrow m/z range (compared with conventional, single-pass TOFMS). The unique characteristics of DOFMS can enable the intact collection of large biomolecules, clusters, and organisms. DOFMS might also play a key role in achieving the long-sought goal of simultaneous MS/MS.

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What do we know and when do we know it?

Two essential aspects of virtual screening are considered: experimental design and performance metrics. In the design of any retrospective virtual screen, choices have to be made as to the purpose of the exercise. Is the goal to compare methods? Is the interest in a particular type of target or all targets? Are we simulating a ‘real-world’ setting, or teasing out distinguishing features of a method? What are the confidence limits for the results? What should be reported in a publication? In particular, what criteria should be used to decide between different performance metrics? Comparing the field of molecular modeling to other endeavors, such as medical statistics, criminology, or computer hardware evaluation indicates some clear directions. Taken together these suggest the modeling field has a long way to go to provide effective assessment of its approaches, either to itself or to a broader audience, but that there are no technical reasons why progress cannot be made.     

What Can We Learn from Molecular Recognition in Protein–Ligand Complexes for the Design of New Drugs?

The understanding of noncovalent interactions in protein–ligand complexes is essential in modern biochemistry and should contribute toward the discovery of new drugs. In the present review, we summarize recent work aimed at a better understanding of the physical nature of molecular recognition in protein–ligand complexes and also at the development and application of new computational tools that exploit our current knowledge on structural and energetic aspects of protein–ligand interactions in the design of novel ligands. These approaches are based on the exponentially growing amount of information about the geometry of protein structures and the properties of small organic molecules exposed to a structured molecular environment. The various contributions that determine the binding affinity of ligands toward a particular receptor are discussed. Their putative binding site conformations are analyzed, and some predictions are attempted. The similarity of ligands is examined with respect to their recognition properties. This information is used to understand and propose binding modes. In addition, an overview of the existing methods for the design and selection of novel protein ligands is given.     

What Differentiates Free Amino Acids and Aminoacyl Residues? An Exploration of Conformational and Lipophilicity Spaces

The objective of this study was to unravel the changes in property space resulting from the amino-acid-to-residue transformation. Conformation-dependent lipophilicity was chosen as the metric to assess changes in property spaces. Phe, Ala-Phe-Ala, Gln, and Ala-Gln-Ala were first submitted to a conformational search strategy using quenched molecular dynamics in order to obtain an efficient sampling of a conformational space. This search was performed for the four electrical forms of the compounds (cationic, zwitterionic, uncharged, and anionic). The virtual lipophilicity (logP) of each conformer was then calculated by the Molecular Lipophilicity Potential (MLP). Similarly, the lipophilicity increment of the Phe and Gln residues in all electrical states and conformers of Ala-Phe-Ala and Ala-Gln-Ala, respectively, were calculated by the MLP. As expected, the results showed a marked expansion in the property space of a tripeptide compared to an amino acid. However, they also revealed a marked reduction in property space resulting from the amino-acid-to-residue transformation.     

What are the relative steric demands of carboxyl and methyl groups?

The relative steric demands of carboxyl and methyl groups are compared by contrasting the difference quantity H _f ^o (g, ArCOOH) — H _f ^o (g, ArCH₃) for a collection of alkylated benzoic acids and toluenes with the value for Ar=C₆H₅, the archetypical (i.e., unsubstituted) benzoic acid and toluene. We conclude that carboxyl and methyl groups are nearly the same size.     

What Is Chromatography, and Can It Be a Single-Phase Process?

The appropriateness of the existence of several definitions of chromatography (as a phenomenon, a science, a process, a separation technique, etc.) is asserted. It is shown that new examples of column-free single-phase versions of field chromatography proposed by Prof. V.G. Berezkin have no relation to chromatography.     

What do Positrons Say about the Structure and Properties of Fluids?

Applications of positron annihilation spectroscopy to fluid state physics and chemistry are discussed. Special attention is paid to problems of surface (interface) layer structure, molecular orientations in the layer, and the effects of freesurface curvature and age on surface tension. Positron investigations of the structure of liquid mixtures, including microheterogeneity studies, are considered.     

Chemical Activation of Lignocellulosic Precursors and Residues: What Else to Consider?

This paper provides the basis for understanding the preparation and properties of an old, but advanced material: activated carbon. The activated carbons discussed herein are obtained from “green” precursors: biomass residues. Accordingly, the present study starts analyzing the components of biomass residues, such as cellulose, hemicellulose, and lignin, and the features that make them suitable raw materials for preparing activated carbons. The physicochemical transformations of these components during their heat treatment that lead to the development of a carbonized material, a biochar, are also considered. The influence of the chemical activation experimental conditions on the yield and porosity development of the final activated carbons are revised as well, and compared with those for physical activation, highlighting the physicochemical interactions between the activating agents and the lignocellulosic components. This review incorporates a comprehensive discussion about the surface chemistry that can be developed as a result of chemical activation and compiles some results related to the mechanical properties and conformation of activated carbons, scarcely analyzed in most published papers. Finally, economic, and environmental issues involved in the large-scale preparation of activated carbons by chemical activation of lignocellulosic precursors are commented on as well.     

Plant wastes and sustainable refineries: What can we learn from fungi?

The valorization of plant wastes allows access to renewable carbon feedstocks without increasing the demand for plant biomass production. Plant wastes are the non-edible residues and waste streams from agriculture, agroindustry and forestry. The chemical diversity and recalcitrance to degradation of such wastes challenge our ability to transform and valorize these resources into value-added compounds. Fungi that thrive on plant tissues have gained a huge diversity of enzymatic toolkits for the finely-tuned degradation of glycan and lignin polymers. Our knowledge on the enzymatic systems developed by fungi now guides innovations for plant waste bioprocessing. Here, we provide an overview of the most recent findings in the hydrolytic and oxidative systems used by fungi for the degradation of recalcitrant plant polymers. We present recent promising success in applying fungal enzymes or fungal fermentations on plant wastes, and discuss the forthcoming developments that could reinforce fungal biotechnology entering a variety of industrial applications.