Biophysical Techniques in Structural Biology.

Over the past six decades, steadily increasing progress in the application of the principles and techniques of the physical sciences to the study of biological systems has led to remarkable insights into the molecular basis of life. Of particular significance has been the way in which the determination of the structures and dynamical properties of proteins and nucleic acids has so often led directly to a profound understanding of the nature and mechanism of their functional roles. The increasing number and power of experimental and theoretical techniques that can be applied successfully to living systems is now ushering in a new era of structural biology that is leading to fundamentally new information about the maintenance of health, the origins of disease, and the development of effective strategies for therapeutic intervention. This article provides a brief overview of some of the most powerful biophysical methods in use today, along with references that provide more detailed information about recent applications of each of them. In addition, this article acts as an introduction to four authoritative reviews in this volume. The first shows the ways that a multiplicity of biophysical methods can be combined with computational techniques to define the architectures of complex biological systems, such as those involving weak interactions within ensembles of molecular components. The second illustrates one aspect of this general approach by describing how recent advances in mass spectrometry, particularly in combination with other techniques, can generate fundamentally new insights into the properties of membrane proteins and their functional interactions with lipid molecules. The third reviewdemonstrates the increasing power of rapidly evolving diffraction techniques, employing the very short bursts of X-rays of extremely high intensity that are now accessible as a result of the construction of free-electron lasers, in particular to carry out time-resolved studies of biochemical reactions. The fourth describes in detail the application of such approaches to probe the mechanism of the light-induced changes associated with bacteriorhodopsin's ability to convert light energy into chemical energy.

[The origins of analysis and of drugs control]. / Les origines de l'analyse et du contrôle des médicaments.

Analytical concerns were quite ancient. As soon as the 12th century, Al-Chayzari searched drugs falsifications. During the 17th century, retort analysis was much practiced. Selective extraction constituted a great progress. During the 18th century, gas volumetric analysis appeared. Descroizilles created volumetric analysis in liquid phase, and that gave him the opportunity for creating acidi-alcalimetry methods. Following the works of Gay-Lussac and Thénard, Liebig invented an apparatus for performing elemental analysis of organic compounds. Michael Tswett created chromatography. Polarimetry was used for dosing glucose in human urines. Kirchhoff and Bunsen created spectroscopic analysis. All these methods allowed the great development of analysis during the 20th century.

Maria Sklodowska-Curie, her life and work - the 150 anniversary of her birthday

Maria Sklodowska was born on November 7, 1867 in Warsaw (Poland). Her parents were teachers. Maria's mother has died in 1878 of tuberculosis. In 1893 and 1894, respectively, Maria was awarded master's degrees in physics and in mathematics from the Sorbonne University. In 1895 Maria married Pierre Curie. In 1897 their daughter Irene was born. Maria investigated rays emitted by uranium salts. She hypothesized that the radiation come from atom and called this phenomenon "radioactivity". In 1898, Maria and Pierre discovered new radioactive elements polonium and radium. In 1902 she isolated pure radium chloride and defined radium atomic mass. In June 1903, Maria supervised by Professor Lippmann was awarded her doctorate in physics from the Sorbonne University of Paris after presentation of the thesis "Investigation of radioactive bodies". In December 1903, Maria was awarded the Nobel Prize in Physics, along with her husband Pierre and Henri Becquerel, for their work on radioactivity. In 1904, the daughter Eve was born. On 19 April 1906, Pierre was killed in a road accident in Paris. In 1910 Maria isolated radium as a pure metal. She also defined an international standard for radioactive emissions (curie), published her fundamental results on radioactivity and textbook of radiology. She also defined the international pattern of radium. In 1911, she won her second Nobel Prize, this time in Chemistry, for her discovery of radium and polonium. In 1914 she was appointed director in the Radium Institute in Paris. During World War I, Maria became the director of the Red Cross Radiology Service and set up France's first military radiology centre. In May 1932 she has attended the official opening ceremony of the Radium Institute in Warsaw. On 4 July 1934, Maria Sklodowska-Curie has died aged 66 years in Sancellemoz sanatorium (France) of aplastic anemia.

The life and work of Geoffrey Tyndale Young.

Geoffrey Tyndale Young was born in England's Peak District in 1915: his father and both grandfathers were pharmaceutical chemists. He graduated from the Universities of Birmingham and Bristol and was a transatlantic scientific liaison officer in the Second World War, shortly after which he was elected to a Fellowship at Jesus College Oxford. He combined peptide synthesis research, undergraduate teaching, and College administration with leadership in European peptide science and was universally respected for his integrity, wisdom, and unflappable diplomacy. A close friend of Josef Rudinger, he attended almost all of the first two dozen European Peptide Symposia 1958-1996. When he retired in 1982, he was appointed an Officer of the Order of the British Empire and was elected an Emeritus Fellow of Jesus College, of which he had been Acting Principal 1973-1977. In retirement, he was instrumental in setting up this journal and steered the formation of the European Peptide Society, of which he was the first chairman. In 1950, he married Janet Mary Baker, later Baroness Young of Farnworth, Leader of the British House of Lords 1982-1983, who died in 2002: they had three daughters who survive him. He died at home in Oxford on 24 May 2014 aged 98.

A conflict of analysis: analytical chemistry and milk adulteration in Victorian Britain.

This article centres on a particularly intense debate within British analytical chemistry in the late nineteenth century, between local public analysts and the government chemists of the Inland Revenue Service. The two groups differed in both practical methodologies and in the interpretation of analytical findings. The most striking debates in this period were related to milk analysis, highlighted especially in Victorian courtrooms. It was in protracted court cases, such as the well known Manchester Milk Case in 1883, that analytical chemistry was performed between local public analysts and the government chemists, who were often both used as expert witnesses. Victorian courtrooms were thus important sites in the context of the uneven professionalisation of chemistry. I use this tension to highlight what Christopher Hamlin has called the defining feature of Victorian public health, namely conflicts of professional jurisdiction, which adds nuance to histories of the struggle of professionalisation and public credibility in analytical chemistry.

Molecular chirality: language, history, and significance.

In this chapter some background material concerning molecular chirality and enantiomerism is presented. First some basic chemical-molecular aspects of chirality are reviewed, after which certain relevant terminology whose use in the literature has been problematic is discussed. Then an overview is provided of some of the early discoveries that laid the foundations of the science of molecular chirality in chemistry and biology, including the discovery of the phenomenon of molecular chirality by L. Pasteur, the proposals for the asymmetric carbon atom by J.H. van 't Hoff and J.A. Lebel, Pasteur's discovery of biological enantioselectivity, the discovery of enantioselectivity at biological receptors by A. Piutti, the studies of enzymatic stereoselectivity by E. Fischer, and the work on enantioselectivity in pharmacology by A. Cushny. Finally, the role of molecular chirality in pharmacotherapy and new-drug development, arguably one of the main driving forces for the current intense interest in the phenomenon of molecular chirality, is discussed.

Natural product analysis over the last decades.

Progress in natural product chemistry has always been strongly linked to innovations in analytical technology. The characterisation of metabolites in complex mixtures requires sophisticated techniques, which should provide good sensitivity and selectivity as well as structural information on the constituents of interest. This review outlines the most important chromatographic and spectral techniques which have been introduced in the field of natural products. Although there has been a very rapid evolution of methods over the last 50 years, the introduction of high-throughput screening programmes require even more efficient and sensitive methodologies which yield adequate on-line information for metabolite structure determination.

Historical brief on composition of human meibum lipids.

Meibomian glands (MG) secrete an oily substance, meibum, that spreads across the ocular surface and mixes with secretions produced by other ocular structures to create a thin film. The protective efficacy of the tear film is believed to be related to the chemical composition of the lipid layer. We reviewed the literature describing the composition of human MG secretions and have provided an overview on methods of collecting meibum samples, methods of lipid analyses, and the results obtained in previous studies. The usefulness and quality of the data obtained about meibum depend on proper sampling and the analytical techniques used. Historically, several methods have been developed, which have yielded contradictory data regarding meibum sample collection and analytical techniques. Based on review of the literature, the major lipids present in meibum are of nonpolar origin: waxes, sterols, and sterol esters, followed by triacylglycerides and fatty acids. The amphiphilic lipids, diacylglycerides, were reported in fewer studies, and monoacylglycerides were reported in only two. Information on the composition of the polar lipids is more controversial. Meibum phospholipids were found in small amounts (16% or less) in some studies, but not in others. Thus, meibum is a complex mixture of lipid molecules. Historical analytical inconsistencies may be partly explained by limitations of past analytical procedures and by the consideration that the tear film lipid layer may have contributing sources other than meibum.

Historical account: Francis William Aston: the man behind the mass spectrograph.

Francis William Aston was among the most accomplished physicists of the 20th century. A Nobel laureate and Fellow of the Royal Society, his research career spanned four decades. During this time, he provided experimental proof for the existence of isotopes of many of the chemical elements and recorded their masses using several, hand-built mass spectrographs. A rather private man who lived alone in Trinity College for much of his adult life, Aston remains a somewhat elusive and mysterious figure. This biography attempts to shed some more light on the man, including his character and his personal life, and particularly how his life was shaped by his childhood, environment and education. It contains previously unpublished material and photographs and complements the biographies of Hevesy and Thomson, following Aston's death, and that by Squires detailing the construction and performance of his mass spectrographs at the Cavendish Laboratory. It is published at a timely juncture, some 100 years after Aston's first arrival at Cambridge.

Samuel James (c1763-1831) of Hoddesdon and the medicinal use of willow bark.

Recognition of the medicinal properties of extracts of willow (Salix sp) bark is usually attributed to Edward Stone (1702-68) of Chipping Norton in Oxfordshire. It was the search for the medicinal compounds that they contained that eventually led to the discovery of salicylic acid, the parent compound of aspirin. Little attention has been given to the work of Samuel James of Hoddesdon who confirmed and extended the results of Stone and who influenced later chemists in their search for specific compounds. Here his work is described and evaluated and his biographical details are recorded.

Spectroscopy, colorimetry, and biological chemistry in the nineteenth century.

The development of colorimetry and spectroscopy in the nineteenth century is described. An account is given of the application of their techniques to biological chemistry during that period.

The measurement of total serum proteins by the Biuret method.

The biuret reaction for proteins provides a simple and precise method for measuring serum proteins; Beer's law is obeyed to at least 10 g per dl. Several stable biuret reagents are available. Hemoglobin is the only important cause of interference which cannot be minimized by use of a sample blank. The mechanism of the biuret reaction is described and attention is drawn to the heterogeneity of the serum proteins and to the use of a certified albumin standard.