Chemical signaling among bacteria and its inhibition

Generations of chemists and biologists have conducted research on natural products and other metabolites produced by bacteria and other microorganisms. This has led to an explosion in knowledge concerning the mechanism by which such natural products are made, ultimately allowing custom redesign of many of these molecules for increased potency and selectivity as therapeutic drugs. Along the way, scientists have begun to appreciate that the bacterial world is teeming with life on a scale hardly conceivable, with constant communication within the bacterial world and with outside neighbors, such as plants and mammals. Only in recent years have some of the signaling molecules that comprise these elaborate forms of communication been characterized in any sort of chemical detail, which has in turn peaked interest in the intricate biology of this micro-world and its interactions with the macro-world.     

Imaging of Hypochlorous Acid by Fluorescence and Applications in Biological Systems

In recent decades, HOCl research has attracted a lot of scientists from around the world. This chemical species is well known as an important player in the biological systems of eukaryotic organisms including humans. In the human body, HOCl is produced by the myeloperoxidase enzyme from superoxide in very low concentrations (20 to 400 μm ); this species is secreted by neutrophils and monocytes to help fight pathogens. However, in the condition called “oxidative stress”, HOCl has the capability to attack many important biomolecules such as amino acids, proteins, nucleotides, nucleic acids, carbohydrates, and lipids; these reactions could ultimately contribute to a number of diseases such as neurodegenerative diseases (AD, PD, and ALS), cardiovascular diseases, and diabetes. In this review, we discuss recent efforts by scientists to synthesize various fluorophores which are attached to receptors to detect HOCl such as: chalcogen‐based oxidation, oxidation of 4‐methoxyphenol, oxime/imine, lactone ring opening, and hydrazine. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively target HOCl and to study the level of HOCl selectivity through emission responses. Virtually all the reports here deal with well‐defined and small synthetic molecular systems. A large number of published compounds have been reported over the past years; this growing field has given scientists new insights regarding the design of the chemosensors. Reversibility, for example is considered important from the stand point of chemosensor reuse within the biological system; facile regenerability using secondary analytes to obtain the initial probe is a very promising avenue. Another aspect which is also important is the energy of the emission wavelength of the sensor; near‐infrared (NIR) emission is favorable to prevent autofluorescence and harmful irradiation of tissue; thus, extended applicability of such sensors can be made to the mouse model or animal model to help image internal organs. In this review, we describe several well‐known types of receptors that are covalently attached to the fluorophore to detect HOCl. We also discuss the common fluorophores which are used by chemist to detect HOCl, Apart from the chemical aspects, we also discuss the capabilities of the compounds to detect HOCl in living cells as measured through confocal imaging. The growing insight from HOCl probing suggests that there is still much room for improvement regarding the available molecular designs, knowledge of interplay between analytes, biological applicability, biological targeting, and chemical switching, which can also serve to further sensor and theurapeutic agent development alike.     

The Views and Influence of Ernst Von Glasersfeld: An Introduction

Research into learners' ideas about science suggests that students often have alternative conceptions about important science concepts. Because of this dissatisfaction, constructivism has been adopted as a theoretical framework by many teachers and researchers, and it has had a curricular influence in many countries. Constructivism is much more than an educational doctrine and we are aware that a ‘science war’ about the possibility of objectivity is in progress. ‘Constructivism’ cannot necessary be a package deal: it must be possible to accept educational suggestions deemed useful without buying all the epistemology or the metaphysical implications. The claim that cognitive agents understand the world by constructing mental representations of it can be a shared suggestion for changing science instruction. Many teachers are much more concerned in finding productive teaching methods than about philosophical questions as if knowledge must be considered an objective representation of the real world or not. We have to ponder if some ideas from the constructivist theory of instruction can help instructors to become better teachers. The pragmatic suggestions that come from the constructivist theory of instruction developed by von Glasersfeld, the leading proponent of radical constructivism, could be a good start in this␣search.     

Science and Arts,Philosophy and Science: Why after All? Why Not?

This perspective summarizes some interdisciplinary aspects of science and the relation to philosophy, also including the basic motivations and aims as they might be discussed with young scientists starting their careers and presented also in the form of a commencement speech. The contents of this speech were repeatedly discussed also with Jack Dunitz, who showed great interest in it, given his broad interests. The speech also referred to an earlier commencement speech by Jack Dunitz in 1989. In the introduction of our essay, we mention the early common history of science and humanities under the name of philosophy. This early history can be traced back to ancient Greek philosophy and the ‘academy’ of Platon in Athens with a history of more than 1000 years until closure in 529 AD, in modern times revived as the National Greek Academy in Athens in the 19th and 20th centuries. Other ‘academies’ in Europe started in the 17th century and had publications under various names involving ‘philosophy’ with a focus on what we call science (natural science) today. After about 1800 there was increasing fragmentation of the various fields of knowledge and philosophy was considered to be part of the modern ‘humanities’ quite separate from science, and the natural sciences were fragmented into physics, chemistry, biology etc., and even finer subdivisions. The essay also describes an effort at ETH Zurich, reintegrating the various subfields of science and also stressing an education of scientists and engineers in the humanities. The essay concludes with a discussion of several global risks for mankind and a scientific imperative to maintain life on Earth. The common aspects and the foundations of all sciences as fields of knowledge aiming for an understanding of the world around us and of human beings as part of it are discussed from various perspectives.     

Recent Advances in the Synthesis of Coumarin Derivatives via Knoevenagel Condensation: A Review

The synthesis of coumarins through Knoevenagel condensation is one of the most important processes in synthetic organic chemistry and medicinal chemistry. Compounds including a coumarin (2-oxo-2H-1-benzopyran) backbone have a wide range of application in the pharmaceutical field. Thus, many methodologies have been developed for the synthesis of this important class of compounds. However, some methods are always associated with toxic and corrosive catalysts, longer reaction time, poor yield, less purity, and by-products along with the desired product. Furthermore, some of these processes are not efficient and environmentally friendly. Therefore, mild, efficient, and environmentally friendly protocols have been developed recently by many scientists for the synthesis of coumarin derivatives via Knoevenagel condensation with good yield and purity. In this review, we have summarized various methods for the synthesis of coumarins via Knoevenagel condensation.     

Four‐Dimensional Space Groups for Pedestrians: Composite Structures

Higher‐dimensional crystals have been studied for the last thirty years. However, most practicing chemists, materials scientists, and crystallographers continue to eschew the use of higher‐dimensional crystallography in their work. Yet it has become increasingly clear in recent years that the number of higher‐dimensional systems continues to grow from hundreds to as many as a thousand different compounds. Part of the problem has to do with the somewhat opaque language that has developed over the past decades to describe higher‐dimensional systems. This language, while well‐suited to the specialist, is too sophisticated for the neophyte wishing to enter the field, and as such can be an impediment. This Focus Review hopes to address this issue. The goal of this article is to show the regular chemist or materials scientist that knowledge of regular 3D crystallography is all that is really necessary to understand 4D crystal systems. To this end, we have couched higher‐dimensional composite structures in the language of ordinary 3D crystals. In particular, we developed the principle of complementarity, which allows one to identify correctly 4D space groups solely from examination of the two 3D components that make up a typical 4D composite structure.     

Enzymatic Conversion of Flavonoids using Bacterial Chalcone Isomerase and Enoate Reductase

Flavonoids are a large group of plant secondary metabolites with a variety of biological properties and are therefore of interest to many scientists, as they can lead to industrially interesting intermediates. The anaerobic gut bacterium Eubacterium ramulus can catabolize flavonoids, but until now, the pathway has not been experimentally confirmed. In the present work, a chalcone isomerase (CHI) and an enoate reductase (ERED) could be identified through whole genome sequencing and gene motif search. These two enzymes were successfully cloned and expressed in Escherichia coli in their active form, even under aerobic conditions. The catabolic pathway of E. ramulus was confirmed by biotransformations of flavanones into dihydrochalcones. The engineered E. coli strain that expresses both enzymes was used for the conversion of several flavanones, underlining the applicability of this biocatalytic cascade reaction.     

Rational Approaches for Drug Designing Against Leishmaniasis

Leishmaniasis has been ignored for many years mainly because it plagues remote and poor areas. However, recently, it has drawn attention of several investigators, and active research is going on for antileishmanial drug discovery. The current available drugs have high failure rates and significant side effects. Recently, liposomal preparations of amphotericin B are available and have proved to be a better drug, but they are very expensive. Miltefosine is one of the few orally administered drugs that are effective against Leishmania. However, it has exhibited teratogenicity, hence, should not be administered to pregnant women. Thus, the search for novel and improved antileishmanial drugs continue. A rational approach to design and develop new antileishmanials can be to identify several metabolic and biochemical differences between host and parasite that can be exploited as drug target. Moreover, many natural products also have significant antileishmanial activity and are yet to be exploited. In the current review, we aim to bring together various drug targets of Leishmania, recent development in the field, future prospects, and hope in the area.     

Doctoral Study Programmes in Europe

For a long time, obtaining a PhD in Belgium and in a number of other European countries was based on the philosophy of ‘learning-by-doing’ under the exclusive supervision of a promoter. The completion of the PhD dissertation usually led to a research or staff position. Now, many of today’s young scientists need to build their career outside the university where employers are as interested in the applicant’s skills as in their knowledge. Highly-qualified research scientists are needed in many sectors of society but require a background in its political, economical and cultural dimensions, and additional management, social and communication skills, including the ability to speak other European languages. However, although the purpose of the doctorate is the creation of a multidisciplinary scientist with broad academic qualifications, many research projects at present are restricted to subjects within a particular discipline. The acquirement of the ‘social’ skills through the ‘learning-by-doing’ concept proves to be very difficult, especially if one considers the increase of graduate students at present times. Therefore, additional study programmes for doctoral students are required. In this paper the doctoral study programme of the University of Antwerpen is described, as well as a short survey of comparable initiatives in Western Europe. Received: 25 January 1996 / Accepted: 7 June 1996     

Doctoral Study Programmes in Europe

For a long time, obtaining a PhD in Belgium and in a number of other European countries was based on the philosophy of ‘learning-by-doing’ under the exclusive supervision of a promoter. The completion of the PhD dissertation usually led to a research or staff position. Now, many of today’s young scientists need to build their career outside the university where employers are as interested in the applicant’s skills as in their knowledge. Highly-qualified research scientists are needed in many sectors of society but require a background in its political, economical and cultural dimensions, and additional management, social and communication skills, including the ability to speak other European languages. However, although the purpose of the doctorate is the creation of a multidisciplinary scientist with broad academic qualifications, many research projects at present are restricted to subjects within a particular discipline. The acquirement of the ‘social’ skills through the ‘learning-by-doing’ concept proves to be very difficult, especially if one considers the increase of graduate students at present times. Therefore, additional study programmes for doctoral students are required. In this paper the doctoral study programme of the University of Antwerpen is described, as well as a short survey of comparable initiatives in Western Europe. Received: 25 January 1996 / Accepted: 7 June 1996     

Modification of Nucleic Acids by Azobenzene Derivatives and Their Applications in Biotechnology and Nanotechnology

Azobenzene has been widely used as a photoregulator due to its reversible photoisomerization, large structural change between E and Z isomers, high photoisomerization yield, and high chemical stability. On the other hand, some azobenzene derivatives can be used as universal quenchers for many fluorophores. Nucleic acid is a good candidate to be modified because it is not only the template of gene expression but also widely used for building well‐organized nanostructures and nanodevices. Because the size and polarity distribution of the azobenzene molecule is similar to a nucleobase pair, the introduction of azobenzene into nucleic acids has been shown to be an ingenious molecular design for constructing light‐switching biosystems or light‐driven nanomachines. Here we review recent advances in azobenzene‐modified nucleic acids and their applications for artificial regulation of gene expression and enzymatic reactions, construction of photoresponsive nanostructures and nanodevices, molecular beacons, as well as obtaining structural information using the introduced azobenzene as an internal probe. In particular, nucleic acids bearing multiple azobenzenes can be used as a novel artificial nanomaterial with merits of high sequence specificity, regular duplex structure, and high photoregulation efficiency. The combination of functional groups with biomolecules may further advance the development of chemical biotechnology and biomolecular engineering.     

Measurement principles for traceability in chemical analysis

 By the definition of the mole as a base unit for amount-of-substance measures within the International System of Units (SI), chemists can make chemical measurements in full compliance with established metrological principles. Since the mole requires exact knowledge of the chemical entity, which is often neither available nor of practical relevance to the purpose of the measurement, the SI units of mass or length (for volume) are unavoidable in the expression of results of many chemical measurements. Science, technology, and trade depend upon a huge and ever increasing number and variety of chemical determinations to quantify material composition and quality. Thus, international harmonization in the assessments of processes, procedures, and results is highly desirable and clearly cost effective. The authors, with relevant experience and responsibilities in Europe and America, have found some consensus in the interpretation of the metrological principles for chemical measurements, but believe open discussion should precede wide implementation by chemical communities. In fostering this dialogue, this paper shows, for instance, that more precise interpretation of the definitions for "traceability," "calibration," and "validation" is needed for present-day chemical measurements. Problems that face scientists in making measurements do not all vanish just by adherence to the SI. However, such compliance can improve communication among chemists and metrologists. Received: 30 June 1995 Accepted: 30 June 1995     

Microgel particles: The structure-property relationships and their biomedical applications

Microgels are crosslinked soft particles with a three-dimensional network structure that are swollen in a good solvent. They have frequently been termed “smart materials” since the size, softness, and interaction forces between particles are tunable by external stimuli such as temperature, pH, or magnetic and electric fields. It is this unique feature that has captured the interest of many scientists across a wide range of disciplines. This brief review covers the basic aspects of the relationships between the network structure and gel properties of the thermally sensitive poly(N-isopropylacrylamide) (pNIPAM) microgels including the phase transition process, the internal structure of microgels, and the phase behavior. Additionally, we highlight the impacts of microgels on the biomedical applications, especially in the gene delivery, cell matrix and differentiation of stem cells. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2995–3003     

Schrödinger's What is Life?—The 75th Anniversary of a Book that Inspired Biology

In his book What is Life?—The Physical Aspect of the Living Cell, Erwin Schrödinger gives a “naïve physicist's” answer to the question “how can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?” Although his book was met with criticism from some of his colleagues, it has had a large impact and has served as profound inspiration for pioneers of molecular biology as well as for later generations of both scientists and laymen.     

Schrödinger's What is Life?—The 75th Anniversary of a Book that Inspired Biology

In his book What is Life?—The Physical Aspect of the Living Cell, Erwin Schrödinger gives a “naïve physicist's” answer to the question “how can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?” Although his book was met with criticism from some of his colleagues, it has had a large impact and has served as profound inspiration for pioneers of molecular biology as well as for later generations of both scientists and laymen.     

From a single analyzer to multiple instruments—The GUM approach

Assessment and expression of analytical quality have become novel spotlights in medical laboratories since accreditation began in the early 1990s, in Europe. Evaluation of uncertainty of measurement by definition was launched in Finland when the Finnish Accreditation Service (FINAS) accredited the first medical laboratories in the mid 1990s. In spite of all the analytical and statistical knowledge which has been available in medical laboratories for years, evaluation of total uncertainty of measurement has not yet caught on. The concept is still unfamiliar to experts and, indeed, little guidance has been available. National and international activities, with good results, can be shown when the educational aspect is considered. The Guide to the Expression of Uncertainty in Measurement (GUM) remains the main document for uncertainty evaluation. Uncertainty of measurement together with target value of uncertainty can be used as a good measure for analytical quality in large or smaller laboratories over time, because it is a quantitative indication and the evaluation is easy to repeat as running practical tools are available.Presented at the 8th Conference on Quality in the Spotlight, 17–18 March 2003, Antwerp, Belgium     

The role of quorum sensing in the pathogenicity of the cunning aggressor Pseudomonas aeruginosa

Recent decades have revealed that many bacterial species are capable of communicating with each other, and this observation has been largely responsible for a paradigm shift in microbiology. Whereas it was previously believed that bacteria lived as individual cells, it is now acknowledged that bacteria preferentially live in communities in the form of primitive organisms in which the behavior of individual cells is coordinated by cell–cell communication, known as quorum sensing (QS). Bacteria use QS for regulation of the processes involved in their interaction with each other, their environment, and, particularly, higher organisms We have focused on Pseudomonas aeruginosa, an opportunistic pathogen producing more than 30 QS-regulated virulence factors. P. aeruginosa causes several types of nosocomial infection, and lung infection in cystic fibrosis (CF) patients. We review the role of QS in the protective mechanisms of P. aeruginosa and show how disruption of the QS can be used as an approach to control this cunning aggressor.     

The Philosophy of Science: Its Possibilities and Limits

Science in the modern world has long since become a factor in the production and reproduction of goods and a condition of life in this world. At the same time, however, it is more than this. Science has therefore become caught-up in an orientation crisis ever since scientists became aware that science can no longer be pursued merely for the sake of pure knowledge, the ideal from ancient times which had been held to be the proper guide for science in its quest for self-understanding. Is the philosopher of science capable of providing the researcher with an answer to the questions what it is he does, and whether or not he is deceiving himself in regard to science and his relationship to it? The philosophy of science has revealed areas which demonstrate that our science is never the smooth and elegant construction composed of observation, experiments, and mathematical and formal techniques which it has often been held to be. It is not the least of the modern philosophy of science's achievements to have demonstrated that science cannot teach man what he should do with it and its results.     

干水：从概念提出到实际应用

通过对干水的发展史考证可知，20世纪中期，科学家研制出一种由二氧化硅颗粒包裹着水滴的干性粉末并将其命名为“干水（Dry Water）”，但在很长的一段时间内并没有引起人们的关注。至21世纪初，关于干水形成机理和制备技术的一系列研究相继展开。随后，干水巨大的潜在应用价值备受人们关注，其在化妆品、水合物储气、催化剂、灭火剂等众多领域的应用得到了一定程度的开发。干水相关技术的发展会使化学物质的利用方式不断创新。干水的相关知识和发展史改变了人们对水的认识，并会成为化学教科书和百科全书的重要内容。     

Fluorophore-assisted carbohydrate electrophoresis in the separation, analysis, and sequencing of carbohydrates

Carbohydrate analysis has traditionally been viewed as a specialty science, performed only in a few well-established laboratories using conventional carbohydrate analysis technology (e.g. NMR, gas chromatography-mass spectroscopy, high-performance liquid chromatography, capillary electrophoresis) combined with the specialized technical training that has been essential for accurate interpretation of the data. This tradition of specialized laboratories is changing, due primarily to an increase in the number of scientists performing routine carbohydrate analysis. As a result, many scientists who are not trained in traditional carbohydrate analytical techniques now need to be able to perform accurate carbohydrate analysis in their own laboratories. This has created a need for technically simple and inexpensive methods of carbohydrate analysis. In this review, we present application vignettes of a technically simple, yet analytically powerful method called fluorophore-assisted carbohydrate electrophoresis (FACE). FACE can be used for performing routine oligosaccharide profiling, monosaccharide analysis, and sequencing of a variety of carbohydrates.