bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormones and reproduction
Authors: Hinson Joy , Raven Peter
Published: September 2023

This chapter focuses on hormones and reproduction. Both male and female reproductive tissues produce steroid hormones as well as gametes. Puberty is a process that is initiated by the development of kisspeptin neurons, which signal the onset of menarche in girls at a body weight of around 47 kg; the exact mechanism is uncertain in boys. The chapter then looks at ovulation in different animals, which may be on a continuous cycle, on a seasonal cycle, or induced by contact with a male. A woman has only a limited number of ova that mature during her reproductive life, whereas men continuously produce new sperm, from puberty until they die. The chapter also considers contraception. Hormones are essential for pregnancy to occur, continue normally, and result in the delivery of a healthy baby.
The use and abuse of hormones
Authors: Hinson Joy , Raven Peter
Published: September 2023

This chapter explores the use and abuse of hormones. When the body is not making enough of a hormone to keep healthy, it is usually necessary to give the hormone as a prescribed medicine. Steroid hormones and thyroxine are usually given as tablets, taken orally, while peptide hormones usually need to be given by injection. The term hormone replacement therapy (HRT) has come to mean the replacement of oestrogens in post-menopausal women, given as a daily tablet containing both oestrogen and progesterone. In spite of significant adverse effects, synthetic corticosteroids are widely used to treat inflammatory illnesses and asthma. The chapter then considers how anabolic androgenic steroids, corticosteroids, growth hormone, and erythropoietin have all been systematically abused throughout sports for decades. Although each has been identified with performance benefits, they also cause harm. Meanwhile, the use of hormones in agriculture remains controversial.
Regulation of gene expression
Authors: Pecorino Lauren
Published: September 2023

This chapter analyzes the molecular components involved in gene expression, including transcription factors, chromatin modifications and chromatin-binding proteins, non-coding RNAs (ncRNAs), and telomeres, and how they can contribute to the processes underpinning cancer. It emphasizes that gene expression may be modulated in various ways: through the regulation of transcription, chromatin structure, and post-transcriptional mechanisms. The chapter also describes the structure of a gene within the context of chromatin in order to elucidate how gene and chromatin structure affects gene expression. Next, the chapter displays the roles of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) that play a role in gene regulation, including post-transcriptional gene expression. It also assesses the effect of telomere position and length on gene expression.
The cell cycle
Authors: Enserink Jorrit M. , Knævelsrud Helene , Robertson Joseph M.
Published: September 2023

This chapter highlights the basic mechanism and regulation of the cell cycle. It defines the cell cycle as the ordered series of events that lead to duplication of the chromosomes and other cellular components, followed by cell division. The chapter emphasizes that the cell cycle is made up of four stages: G1, S phase, G2, and M phase. G1, S phase, and G2 constitute the cycle phase called interphase. The genetic material of a cell is replicated in S phase (DNA synthesis), and M phase involves partitioning of the cell and genome. The chapter then introduces the cyclins and cyclin-dependent kinases (CDKs), the main players in the cell cycle. It also investigates the molecular mechanisms involved in the regulation of the cell cycle. Next, it describes specific mutations that affect the cell cycle and play a role in carcinogenesis. It also discusses therapeutic strategies that target molecules of the cell cycle.
Electronic Structure
Authors: Jenkins Stephen J.
Published: September 2023

Introduction

The preceding chapters provide an overview of surface thermodynamics, symmetry, and structure—all from the perspective of the atoms and molecules involved. Conspicuously, we have avoided any discussion of the electrons that bind those atoms and molecules together, even though it is their distribution—in space...
Periodicity and the s- and p-Block Elements
Authors: Norman Nicholas C.
Published: September 2023

Periodicity and the s- and p-block elements begins by looking at atomic structure and the periodic table. Then chapters look at periodicity in the atomic properties of the elements, periodicity in the properties of the elements, and general features of p-block element compounds. The text moves on to examine compounds of the p-block elements, acids and bases, structure, and theories and models.
Introduction
Authors: Norman Nicholas C.
Published: September 2023

This chapter provides an overview of ideas on atomic structure which lead to an understanding of why the periodic table has the form that it does. The periodic table was initially constructed based on a consideration of atomic weight (nowadays referred to as relative atomic mass) and periodic trends in the chemical behaviour of the elements. It was therefore arrived at empirically, and only later were the underlying reasons for its structure understood with the development of quantum theory in the early twentieth century. The chapter then looks at the Schrödinger wave equation, which is used to describe the behaviour or properties of electrons in atoms. It also considers wavefunctions for the hydrogen atom; the energies of orbitals; and polyelectronic atoms. Ultimately, the chapter explains some of the key features of the periodic table, particularly in terms of the relative positions of the s-, p-, and d-blocks.
General features of s- and p-block element compounds
Authors: Norman Nicholas C.
Published: September 2023

This chapter assesses s- and p-block element compounds and their properties. It begins by looking at halides, which is a large and diverse group of compounds, particularly in terms of the variety of structural types encountered. Halides include fluorides and chlorides. The chapter then considers ionic compounds, element oxides, and element hydrides. All the hydrides are molecular covalent species, but the trends in melting and boiling points are worthy of comment. In Group 14, one sees a progression to higher melting and boiling points as the group is descending resulting from the increasing van der Waals forces between the molecules. This is also largely the case for the Group 16 hydrides but with the obvious exception of H2O. The explanation for this feature is the extensive intermolecular hydrogen bonding between oxygen lone pairs and hydrogen, this being that much greater for the lighter element oxygen due to its high electronegativity.
Special Features of Mammalian Systems
Authors: Davies Jamie A.
Published: September 2023

This chapter introduces the special features that distinguish mammalian systems from other systems. It lists differences and similarities between bacteria, yeasts, and mammals in terms of features relevant to the design of synthetic biological devices and projects. It describes the typical structure of a mammalian gene, including its controlling elements. It also explains how the transcription of a typical mammalian gene is activated and how mammalian gene expression can be controlled by chromatin modification before looking at its significance to synthetic biology. The chapter gives an outline sketch of how mammalian gene expression can be specific to particular cell types and highlights the function of major compartments in mammalian cells. It reviews the main barriers to the spread of biomolecules within the mammalian body and clarifies how the mammalian adaptive immune system works and how its presence can be a limitation to synthetic biology.
Mammalian Synthetic Biology as a Research Tool
Authors: Davies Jamie A.
Published: September 2023

This chapter outlines the virtuous cycle in which basic science informs the design of synthetic systems, and new synthetic systems can be used to discover more basic science. It cites the two broad ways in which synthetic biology is applied to basic science: as a discovery tool and as a means of testing theories. It also elaborates on how synthetic biological techniques can allow experimenters to use light to activate specific neurons in an animal brain, defining RASSLs and demonstrating how they can be used to dissect complex signal pathways. The chapter examines the strengths and weaknesses of the methods of hypothesis testing, covering gene knockout, computer modelling, and modelling by synthetic biology. It discusses the concept of a functional motif and cites an example of a synthetic biological realization of a gene network motif.
Genetic Medicine for Adult Onset Disease
Authors: Jennings Barbara , Thalange Nandu , Willis Gavin
Published: September 2023

This chapter discusses genetic medicine for adult onset disease. It explores the concept of variable penetrance which is linked to expressivity. The chapter cites the process of using genetic testing for type 1 hereditary haemochromatosis. It also compares diseases with monogenic, polygenic, and multifactorial causes. Moreover, it looks at the differences between discontinuous traits and continuous traits. It then explores methods used to identify alleles with additive effects on complex disease phenotypes. The chapter also notes that polygenic risk score (PRS) is the probabilistic information achieved using information from all of the genome-wide association study (GWAS) genetic data points.
Adiabatic changes
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter describes adiabatic processes, which occur without the transfer of energy as heat. It focuses on reversible adiabatic changes involving perfect gases. The temperature of a gas falls when it expands adiabatically in a thermally insulated container. Work is done, but as no heat enters the system, the internal energy falls, and therefore the temperature of the gas also falls. In molecular terms, the kinetic energy of the molecules falls as work is done, so their average speed decreases, and hence the temperature falls too. The chapter then looks at how an adiabat is a curve showing how pressure varies with volume in an adiabatic process.
Thermodynamic aspects of phase transitions
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter examines how thermodynamic arguments explain the appearance of phase diagrams and can be used to make predictions about the effect of pressure on phase transitions. They provide insight into the properties that account for the behaviour of matter under different conditions. The effect of temperature and pressure on the chemical potential of a substance in each phase depends on its molar entropy and molar volume, respectively. The chemical potential of a substance decreases with increasing temperature in proportion to its molar entropy; it increases with increasing pressure in proportion to its molar volume. Meanwhile, the vapour pressure of a condensed phase increases when pressure is applied. The chapter then looks at the Clapeyron equation, which is an exact expression for the slope of a coexistence curve. The Clausius–Clapeyron equation is an approximate expression for the coexistence curve of a condensed phase and its vapour.
Phase diagrams of binary systems: liquids
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter focuses on phase diagrams of systems of liquids. It begins by looking at vapour pressure diagrams. The partial vapour pressures of the components of an ideal mixture of two volatile liquids are related to its composition by Raoult's law. The chapter then considers temperature–composition diagrams, in which the boundaries show the composition of the phases that are in equilibrium at various temperatures. The lever rule is used to deduce the relative abundances of each phase in equilibrium. The chapter also discusses how the separation of a liquid mixture by fractional distillation involves repeated cycles of boiling and condensation. An azeotrope is a liquid mixture that boils without change of composition. Finally, the chapter examines liquid–liquid phase diagrams.
The equilibrium constant
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter explores equilibrium constants, which lie at the heart of chemistry and are a key point of contact between thermodynamics and laboratory chemistry. It develops the concept of chemical potential and shows how it is used to account for the equilibrium composition of a reaction mixture. The equilibrium composition corresponds to a minimum in the Gibbs energy. By locating this minimum, it is possible to establish the relation between the equilibrium constant and the standard Gibbs energy of reaction. The chapter differentiates between exergonic and endergonic reactions. The reaction Gibbs energy is the slope of the plot of Gibbs energy against extent of reaction. Meanwhile, the equilibrium constant is the value of the reaction quotient at equilibrium.
Vibrational motion
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter focuses on molecular vibration, which plays a role in the interpretation of thermodynamic properties. It introduces the ‘harmonic oscillator’, a simple but very important model for the description of vibrations. The chapter shows that the energies of an oscillator are quantized and that an oscillator may be found at displacements that are forbidden by classical physics. The energy levels of a quantum mechanical harmonic oscillator are evenly spaced. The chapter then explains how the wavefunctions of a quantum mechanical harmonic oscillator are products of a Hermite polynomial and a Gaussian (bell-shaped) function. A quantum mechanical harmonic oscillator has zero-point energy, an irremovable minimum energy.
Computational chemistry
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter is concerned with computational chemistry, which refers to the use of computers to predict molecular structure and reactivity. It considers the central aim of electronic structure calculation to solve the electronic Schrödinger equation. Hartree-Fock formalism guides the calculation of molecular orbitals, while density functional theory (DFT) offers greater precision and computational efficiency. The chapter also details the features of Roothaan equations, a priori method, semi-empirical procedure, Hohenberg–Kohn theorem, Gaussian-type orbitals, and the Kohn-Sham orbital. It considers the evaluation and approximation of the integrals, which are fixed throughout the calculation because they depend only on the choice of basis.
Pulse techniques in NMR
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter covers pulse techniques in nuclear magnetic resonance (NMR). Sequences of pulses of radiofrequency radiation manipulate nuclear spins, leading to the efficient acquisition of NMR spectra and the measurement of relaxation times. Relaxation primarily refers to the process by which the magnetization returns to its equilibrium value. The chapter elaborates on the nuclear Overhauser effect, which makes use of the relaxation caused by the dipole-dipole interaction of nuclear spins, referencing the modification of the intensity of one resonance by the saturation of another. It also mentions how the modern implementation of NMR spectroscopy triggers many possibilities for the development of more sophisticated experiments.
Molecular energies
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter focuses on the concept of molecular energies. It clarifies that a partition function is the thermodynamic version of a wavefunction, which contains all the dynamical information about a system. Thus, a partition function contains all the thermodynamic information about a system. The chapter discusses the equation and calculation surrounding the mean energy of molecules from a knowledge of the partition function. It considers the contributions of the fundamental modes of motion: translation, rotation, vibration, electronic, and electron spin. Additionally, individual contributions to the mean molecular energy from each mode of motion are calculated from the relevant partition functions.
The optical properties of solids
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter talks about spectroscopy, which is a key tool for exploring the electronic structure of solids. It highlights spectroscopic observations that explore the electronic band structure of a solid material and give insight into phenomena that arise from the interactions present in such materials. It also looks at how some solids being subjected to very intense radiation respond nonlinearly, leading to useful phenomena such as ‘frequency doubling’. The chapter considers the ever-increasing importance of optical properties of solids in modern technology for the generation of light and the propagation and manipulation of information. It demonstrates how optical properties of molecules in solids differ from those of isolated molecules, which is a result of the interaction of their transition dipoles.
Integrated rate laws
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter focuses on integrated rate laws as the solutions of the differential equations that describe rate laws. It explains how integrated rate laws are used to predict the concentrations of species at any time after the start of the reaction and to provide procedures for measuring rate constants. It also highlights the use of the integrated rate law to predict the composition of a reaction mixture as it approaches equilibrium. The chapter considers the integrated rate law as the basis of determining the order and rate constants of a reaction, which is a necessary step in the formulation of the mechanism of the reaction. The integrated rate law shows how the concentrations of reactants and products change with time.
Adsorption and desorption
Authors: Atkins Peter , de Paula Julio , Keeler James
Published: September 2023

This chapter looks at the extent to which molecules attach themselves to a surface, which is crucial to understanding the way in which a surface influences chemical processes. It discusses the extent of adsorption that can be explored with the aid of some simple models that allow quantitative predictions to be made about how the extent of surface coverage varies with both pressure and temperature. It also demonstrates how surfaces can affect the rates of chemical reactions by assessing the extent of surface coverage and the factors that determine the rates at which molecules attach to and detach from solid surfaces. The chapter outlines the extent of surface coverage that can be expressed in terms of isotherms derived on the basis of dynamic equilibria between adsorbed and free molecules.
Cancer Genomics
Authors: Chappell Lia , Lindsay Sarah J , Jones Phil , Parkhill Julian , Roberts Jonathan , Holroyd Nancy , Szpak Michal , Gale Francesca
Published: September 2023

This chapter discusses cancer genomics, which is one of the fastest-moving areas of medical research and is having a direct impact on people's lives. Cancer is a disease in which cells divide in excess, generating a lump, known as the primary tumour. A key feature of cancer is that the cells in the lump spread, invading the neighbouring normal tissues and blood and lymphatic vessels, allowing them to colonize distant organs, forming distant secondary tumours. Both primary and secondary tumours may cause symptoms as they penetrate and grow into normal tissues. The genome changes in cancers include single nucleotide changes, amplifications or deletions of regions of chromosomes, and chromosome rearrangements that may join genes together. The chapter considers how understanding the genome of cancer cells can help us prevent and treat cancer, and improve the survival and quality of life of patients.
Genomics: Reading and Writing Genomes
Authors: Chappell Lia , Lindsay Sarah J , Jones Phil , Parkhill Julian , Roberts Jonathan , Holroyd Nancy , Szpak Michal , Gale Francesca
Published: September 2023

This chapter explores the incredible advances which have taken place—and are still taking place—in the technologies involved in DNA sequencing and in DNA manipulation. The invention of DNA sequencing technology enabled DNA to be read for the first time in the 1970s, using a process known as Sanger sequencing. The development of capillary sequencing then helped to speed up many genome sequencing projects, as it is faster and cheaper than the previous methods. Other developments include high-throughput short-read sequencing technologies and long-read sequencing technologies. Meanwhile, editing DNA sequences in cells using protocols such as CRISPR–Cas9 allows researchers to change the DNA sequences within cells, so they can test what specific DNA sequences do within cells and potentially change faulty sequences or improve outcomes. Writing entirely new genomes is now possible for simple cells, as it is now possible to join together long synthetic DNA sequences.
Structures of Organic Compounds
Authors: Elliott Mark C.
Published: September 2023

Let’s start with the absolute basics—drawing structures. We need to consider the different conventions that are in common usage, and what the benefits and disadvantages are of each.

Simply reading through this chapter will not make you good at drawing structures. Every reader will probably...
Always Draw Structures with Realistic Geometry
Authors: Elliott Mark C.
Published: September 2023

In the previous chapter, I mentioned the importance of forming good habits. I want to formalize this by including short chapters focused only on this one theme. Here is the first one!
Electronegativity, Bond Polarization, and Inductive Effects
Authors: Elliott Mark C.
Published: September 2023

When we look at a structure, we need to consider how the electrons are distributed within the structure, so that we can predict how the structure will react with different reagents under various different reaction conditions.

The simplest parameter that affects electron distribution is electronegativity....
Nucleophilic Substitution at Saturated Carbon
Authors: Elliott Mark C.
Published: September 2023

What is A Substitution Reaction?

Quite simply, a substitution reaction is where one group on an atom is replaced with another group.

When we are talking about a substitution reaction at saturated (sp3) carbon, the following process is a substitution. We are replacing...
Thermodynamic Definitions
Authors: Elliott Mark C.
Published: September 2023

We now need to start building the framework of how far and how fast a reaction will go. Let’s start slowly, and consider the energy differences between starting materials and products.
Calculating Enthalpy of Reaction from Bond Dissociation Energy
Authors: Elliott Mark C.
Published: September 2023

The Purpose of The Exercise

In my experience, it is pretty rare for an organic chemist to carry out one of these calculations. However, they will look at a reaction and intuitively know whether it is likely to be endothermic or exothermic...

They can...
Carbocations 2—More Factors Affecting Stability
Authors: Elliott Mark C.
Published: September 2023

In Basics 16, we introduced the idea that the number of alkyl groups attached to a carbocation carbon atom will significantly affect its stability. Of course, there are many different groups that we can attach to a carbocation carbon atom, and they will...
Resonance
Authors: Elliott Mark C.
Published: September 2023

What Does it Mean?

The first common error is a fundamental misunderstanding of what resonance structures mean. I sometimes hear students talk about a compound ‘resonating between two structures’.

This is understandable. The word ‘resonance’ already has meaning for you.

Have another look at the...
The Hammond Postulate
Authors: Elliott Mark C.
Published: September 2023

The Hammond Postulate—An Explanation

The Hammond postulate is a truly elegant and simple idea. When I was taught it, I was taught the words. I don’t think I really understood the implications of them. Let’s start with the words anyway.

‘If two states, as, for...
Conjugation and Stability—The Evidence
Authors: Elliott Mark C.
Published: September 2023

In Basics 10 we presented conjugation and resonance. One of the key points was that conjugation of (overlap between) double bonds imparts additional stability to compounds.

As a scientist, it is important that you understand the facts and theories, but it is also important that...
Acid Catalysis in Organic Reactions Part 1
Authors: Elliott Mark C.
Published: September 2023

Introduction

We are going to have to do this one in two stages. We don’t know enough (yet) to give a full treatment of the problem, but it’s too important to not make a start!

Acid catalysis is widely used to increase the rates of...
Bonding Beyond Hybridization
Authors: Elliott Mark C.
Published: September 2023

When we think of electrons and orbitals, we use quantum mechanics. It is impossible to accurately solve the Schrödinger equation for anything other than the simplest systems. For real organic molecules, you cannot do it at all. Therefore, everything you will ever be told about...
Bond Lengths and Strengths
Authors: Elliott Mark C.
Published: September 2023

Much of the focus of this book is building patterns and habits. I have tried to keep the factual information to a minimum, but of course it is still there.

Here is the problem. A chemical bond is between 1.0 and 1.6 Å in length....
pKa
Authors: Elliott Mark C.
Published: September 2023

Arguably, this is even more important than the previous one. Remember that we use the pK
a scale to quantify the stability of carbanions.

If it isn’t stable (high pKa) then it won’t be easy to form.

I’m not going to...
Isomerism in Organic Chemistry—Configurational Isomers
Authors: Elliott Mark C.
Published: September 2023

Introduction

The study of the three-dimensional shape of compounds is really important. The three-dimensional shape of a compound can affect many properties, most significantly the biological properties. In the most extreme case, one stereoisomer of a compound could cure a person of a disease. Another...
Stereochemical Errors
Authors: Elliott Mark C.
Published: September 2023

Introduction

Stereochemistry causes a lot of problems! The reasons for this are very simple, but they are not always easy to fix—at least not quickly!

A good grasp of stereochemistry requires you to be able to look at a structure and to visualize what it...
Drawing More Complex Cyclohexanes
Authors: Elliott Mark C.
Published: September 2023

The Point of The Exercise

We drew quite a lot of cyclohexanes in Practice 12, but when you get right down to it, those examples were quite easy. There was only one ring, so you just had to work out whether there were...
Cyclohexanes
Authors: Elliott Mark C.
Published: September 2023

The errors commonly made when drawing cyclohexanes have been mentioned already, so I just want to summarize them briefly here.
Elimination Reactions
Authors: Elliott Mark C.
Published: September 2023

It isn’t easy to split elimination reactions into mechanisms and stereochemistry, although Applications 4 does focus on the latter aspect. We will still see the stereo-chemical implications of the E2 mechanism in this chapter as we look at the molecular orbitals.

For each of the...
Enthalpy Changes for Reactions Involving Anionic Species
Authors: Elliott Mark C.
Published: September 2023

A Strange Statement

The two statements below appear to be direct contradictions. How can they possibly both be correct? The devil is in the details.

Addition of HBr across an alkene can be exothermic. Elimination of HBr to form an alkene can also be exothermic....
Elimination Reactions of Cyclohexanes
Authors: Elliott Mark C.
Published: September 2023

Just as we did with substitution reactions in Applications 3, we will take what we know about elimination reactions and apply them to cyclohexanes.

Why Are Cyclohexanes Special?

To reiterate the comment that I made last time, they are not. We should just remind...
Building Skills
Authors: Elliott Mark C.
Published: September 2023

This chapter presents a series of worked problems within organic chemistry that vary in scope and complexity and require the basic application of knowledge to predict the outcomes of reaction. It includes activities that require the drawing of correct curly arrows showing either a substitution or an elimination reaction. It also presents a question on whether it is possible for all nine C–H bonds in the t-butyl carbocation to simultaneously overlap with the vacant p orbital. The chapter reviews the thermodynamics of reactions involving charged species and considers the implications of acid catalysis with a strong acid and a weak acid. It compares two processes that established that the activation energy from the protonated alcohol is significantly lower.
The Fürst–Plattner Rule
Authors: Elliott Mark C.
Published: September 2023

Introduction

This is a topic that you don’t normally encounter at this level. It concerns the ring-opening of cyclohexane epoxides by nucleophiles.

The fact that there is a ‘rule’ associated with it doesn’t make it more complicated.

If you understand cyclohexane conformers, you will be...
Acid Catalysis in Organic Reactions Part 2
Authors: Elliott Mark C.
Published: September 2023

Answer 1

Here is the equilibrium again.

We know that...
The Fürst–Plattner Rule
Authors: Elliott Mark C.
Published: September 2023

Answer 1

We looked at epoxide opening reactions in
Worked Problem 5
.

In terms of mechanism, if we have an SN1 mechanism, we would expect attack at carbon 1, since this is where we would form a more stable carbocation. Product ...
Introduction To Cell Signalling
Authors: Hancock John T.
Published: September 2023

This chapter explains why the study of cell signalling is important and instrumental to modern biology and traces the history of cell signalling. It outlines the principles behind the workings of cell signalling, which can be applied to all living systems, and discusses a selection of diseases caused by cell signalling dysfunction. It also describes cell signalling as a regulatory system that enables cells to control their inner workings and perceive their environment and respond when changes are required. The chapter highlights the need of cells of multicellular organisms to respond to the messages created by other cells and to conditions on their outsides. It demonstrates how cells communicate between each other and influence each other's activities through the release and reception of hormones.
Signals and Their Perception
Authors: Hancock John T.
Published: September 2023

This chapter looks at a variety of signalling molecules and discusses how signals are generated and perceived in the absence of a receptor. It examines different types of receptors that transmit messages into or across cells. It also describes cells that are continually bombarded by molecules and environmental factors to which they may need to respond and recognize what they are responding to. The chapter emphasizes the urgency of perception to the survival of the cell itself and to multicellular organisms as a whole. It talks about a protein known as a receptor that has a structure tailored to interact in some way with the arriving signal or signalling molecule, which is referred to as a ligand.
Modifications to Proteins That Control Cell Signalling
Authors: Hancock John T.
Published: September 2023

This chapter explores why post-translational modifications (PTMs) of proteins are important and analyses the action and consequences of phosphorylation. It cites examples of cell signalling that involve phosphorylation and demonstrates the role of other modifications of proteins and their ramifications for protein function. It also discusses the importance of proteins in cells, as they may have a structural role as keratin and collagen or catalytic roles that involve metabolism. The chapter outlines the levels of control that are available to cells in order to ensure that the levels of actions of proteins are appropriate. It points out how cells can control the rates of expression of the genes that encode proteins.
Future Challenges and Perspectives In Cell Signalling
Authors: Hancock John T.
Published: September 2023

This chapter looks at selected methods for measuring the levels of cell signalling components and discusses the notion of compartmentalization. It describes how signalling is a balance and states that threshold levels allow signalling to be propagated. It also explains how cell signalling systems can be manipulated to improve human health and agriculture outputs. The chapter traces the history of medicine, which has produced numerous drugs that have their targets in cell signalling mechanisms. It highlights that a significant amount of effort is now focused on the manipulation of G protein-coupled receptors (GPCRs), which appears promising for drug development. Treatments that target cell signalling in plants will likely have a transformative impact on agriculture, as they may allow for crops to be improved where soils are contaminated or where climate change has an effect.
The Story of Anaesthesia
Authors: Fullick William , Fullick James
Published: September 2023

This chapter focuses on the effects and development of anaesthesia. It explains that nearly all drugs in anaesthesia act on two basic principles of activation or suppression of cellular receptors and dependence on a concentration gradient. Modern anaesthesia involves precise doses of specially designed drugs that obliterate consciousness and provide pain relief. The chapter then looks at the equipment and techniques concerned with the anaesthetist at work. It looks into the debates surrounding anaesthetic drugs and how they work, and it references the relationship between GABA receptors with globally decreased neurone transmission within the brain and other organ systems.
From Food to Faeces
Authors: Fullick William , Fullick James
Published: September 2023

This chapter details the processes of digestion, which is handled using a complex series of feedback loops. It explains that the gastrointestinal tract (GI tract) is a formidably complicated collection of interdependent organs. The organs of the gastrointestinal tract work from the mouth to the anus to break down and absorb the nutrients found in consumed food. Thus, any diseases affecting any part of the GI tract can have significant effects on people's nutritional state. The chapter explains that surgery can provide treatment for the disease, but the procedure might trigger other complications, such as colostomies or shortened bowels.
Protein structure and function
Authors: Patrick Graham L.
Published: September 2023

This chapter focuses on primary structure, which is the order in which amino acids are linked together in a protein. The secondary structure of a protein refers to regions of ordered structure within the protein. The chapter highlights proteins that contain two or more subunits and have a quaternary structure that defines how the subunits are arranged with respect to each other. It also looks at secondary, tertiary, and quaternary structures. These are formed to maximize favourable intramolecular and intermolecular bonds and to minimize unfavourable interactions. The chapter analyzes amino acids with polar residues. These are favoured on the outer surface of a protein because this allows hydrogen-bonding interactions with water. The chapter talks about transport proteins which carry essential polar molecules across the hydrophobic cell membrane.
Enzymes as drug targets
Authors: Patrick Graham L.
Published: September 2023

This chapter focuses on how drugs target enzymes and inhibit their action. It discusses enzyme inhibition and shows that this is reversible if the drug binds through intermolecular interactions, noting how irreversible inhibition results from drug reactions with the enzyme. This then forms a covalent bond. The chapter also examines allosteric inhibitors which bind to an allosteric binding site and alter the shape of the enzyme such that the active site is no longer recognizable. The chapter highlights suicide substrates, which are molecules that act as substrates for a target enzyme and are converted into highly reactive species as a result of the enzyme-catalysed reaction mechanism. It cites enzyme inhibitors and shows that these are used in a wide variety of medicinal applications.
Receptors as drug targets
Authors: Patrick Graham L.
Published: September 2023

This chapter shows the factors that determine whether a drug acts as an agonist or an antagonist. It examines if it is possible to predict whether a new drug will act as one or the other. It explains that agonists are compounds that mimic the natural ligand for the receptor, while antagonists are agents which bind to the receptor and block binding of the natural ligand. The chapter also considers what happens when a small molecule such as a drug or a neurotransmitter interacts with a receptor protein. The chapter talks about desensitization, which occurs when an agonist is bound to its receptor for a long period of time. It also explains the process of sensitization that occur when an antagonist is bound to a receptor for a long period of time.
Nucleic acids as drug targets
Authors: Patrick Graham L.
Published: September 2023

This chapter concentrates on the mechanism of the action of drugs which target nucleic acids in the areas of antibacterial and anticancer therapy. It considers drugs that interact with DNA and shows how these categorized into intercalating agents, topoisomerase poisons, alkylating agents, chain cutters, and chain terminators. It also highlights intercalating drugs which contain planar aromatic or heteroaromatic ring systems that can slide between the base pairs of the DNA double helix. The chapter looks at bleomycins, which are intercalating drugs that form complexes with ferrous ions and generate reactive oxygen species. These cleave the strands of DNA. The chapter considers etoposide and teniposide as non-intercalating drugs which act as topoisomerase II poisons.
Pharmacokinetics and related topics
Authors: Patrick Graham L.
Published: September 2023

This chapter explores the three phases involved in drug action. First is the pharmaceutical phase, which includes the disintegration of a pill or capsule in the gastrointestinal tract (GIT), the release of the drug, and its dissolution. Second is the pharmacokinetic phase, which includes absorption from the GIT into the blood supply, third is the pharmacodynamic phase, which involves the mechanism by which a drug interacts with its molecular target and the resulting pharmacological effect. The chapter discusses the four main issues in pharmacokinetics: absorption, distribution, metabolism, and excretion (ADME). It reviews highly polar drugs which can be orally active if they are small enough to pass between the cells of the gut wall. These are recognized by carrierproteins, or are taken across the gut wall by pinocytosis.
Drug discovery: finding a lead
Authors: Patrick Graham L.
Published: September 2023

This chapter looks at what happens from the moment that a pharmaceutical company or university research group initiates a new medicinal chemistry project through to the identification of a lead compound. It focuses on pharmaceutical companies which tend to concentrate on developing drugs for diseases prevalent in developed countries. These comapnies also aim to produce compounds with better properties than existing drugs. It also shows how a molecular target influences a particular disease when affected by a drug. The chapter discusses compounds that can be tested by nuclear magnetic resonance (NMR) spectroscopy as a result of their affinity to a macromolecular target. It defines a lead compound as a structure that shows a useful pharmacological activity and can act as the starting point for drug design.
Artemisinin and related antimalarial drugs
Authors: Patrick Graham L.
Published: September 2023

This chapter provides a background on the ancient disease malaria, which is caused by a protozoal parasite carried by mosquitoes and is transmitted between mosquitoes and humans by mosquito bites. It explains that the malarial parasite is a microorganism that belongs to the Plasmodium genus and includes four species: P. vivax, P. falciparum, P. ovale, and P. malariae. The chapter also considers P. falciparum as the most dangerous of malarial parasites which can result in death. The chapter discusses the Chinese plant Artemisia annua, which was recorded in 1596 as a treatment for chills and fever, symptoms of malaria. It details how Artemisia annua was isolated and identified as artemisinin in 1972 and was found to be effective against the particularly dangerous chloroquine-resistant P. falciparum.
Fosmidomycin as an antimalarial agent
Authors: Patrick Graham L.
Published: September 2023

This chapter focuses on the antimalarial agent fosmidomycin, which was isolated from the bacterium Streptomyces lavendulae in the late 1970s. It describes the structure of fosmidomycin and shows that it consists of a 3-carbon linker between the hydroxamic acid and phosphonate group. These are crucial to its antimalarial activity. It also recounts how fosmidomycin was originally considered as a potential antibiotic for the treatment of urinary tract infections until it gained more interest in its potential as an antimalarial agent. The chapter highlights the Plasmodium enzyme DOXP reductoisomerase (DXR), which is the molecular target for fosmidomycin. DXR is responsible for catalysing the second step of the non-mevalonate biosynthetic pathway to isoprenes.
In silico drug design
Authors: Patrick Graham L.
Published: September 2023

This chapter looks at in silico drug design and how various software programs are used to assist the drug design process. It focuses on molecular modelling, which is key to structure-based drug design and de novo drug design. It also cites examples of how in silico drug design and specialist software programs are used in medicinal chemistry. The chapter examines molecular mechanics programs that use equations based on classical physics to calculate force fields, including atoms that are treated as spheres and bonds as springs. It discusses how energy minimization is carried out on any molecule constructed with molecular modelling software. This involves alteration of bond lengths, bond angles, torsion angles, and non-bonded interactions until a stable conformation is obtained.
Anticancer agents
Authors: Patrick Graham L.
Published: September 2023

This chapter introduces cancer cells which have defects in the normal regulatory controls governing cell growth and division. These arise from mutations resulting in the activation of oncogenes and the inactivation of tumour suppression genes. The chapter describes defects in signalling pathways that are commonly found in cancer cells, stimulating cell growth and division that are a result of the overproduction of a crucial protein in the pathway or the production of an abnormal protein. It also shows how the production of regulatory proteins that suppress cell growth and division is suppressed in many cancers. The chapter talks about cancer cells which can have intrinsic or acquired resistance to anticancer drugs. It explains how resistance may be due to poor uptake of the drug, increased production of the target protein, mutations that prevent the drug binding to its target, alternative metabolic pathways, or efflux systems that expel drugs from the cell.
Protein kinase inhibitors as anticancer agents
Authors: Patrick Graham L.
Published: September 2023

This chapter discusses protein kinases, which are enzymes that phosphorylate specific amino acid residues in protein substrates. It aruges that protein kinases are important targets for anticancer drugs as they are involved in signal transduction pathways controlling cell growth and division. It also highlights the hinge region of a protein kinase that links two distinct lobes of the protein kinase and is often involved in the binding of kinase inhibitors. The chapter analyzes gatekeeper residue, which is an amino acid residue located at the entrance of a hydrophobic pocket and is important in binding some kinase inhibitors. It describes the size of the gatekeeper residue and its importance for selectivity as it determines whether inhibitors can access the hydrophobic pocket.
Cardiovascular drugs
Authors: Patrick Graham L.
Published: September 2023

This chapter focuses on cardiovascular drugs, which are used to treat hypertension, cardiac problems, atherosclerosis, and thrombosis. It details how the renin-angiotensin-aldosterone system (RAAS) cascade produces angiotensin II, which is a potent vasoconstricting hormone. It also mentions renin and angiotensin-converting enzyme (ACE), which are key enzymes in the RAAS cascade and are important targets for antihypertensive agents. The chapter talks about angiotensin II, which produces its vasoconstrictive effects by activating the angiotensin II receptor (AT1), making this receptor an important target for antihypertensive agents. Finally, the chapter provides a background on vasodilators, which relieve hypertension by dilating blood vessels and reducing blood pressure.
Current research into antidepressant agents
Authors: Patrick Graham L.
Published: September 2023

This chapter introduces major depression, which is a common ailment that affects up to 10% of the population and leads to approximately 700,000 suicides each year. It points out how sufferers of long-term depression are more prone to other diseases and their lifespan can be shortened. It also discusses research into novel agents and shows how this is designed to interact with transport proteins for dopamine, serotonin, and noradrenaline, with adrenergic receptors, and with serotonin receptors. The chapter reviews the research project that is aimed at discovering 5-HT7 antagonists. It cites vortioxetine as an example of an antidepressant with high affinity (Ki) for a number of serotonin-related targets and acts as an antagonist at the 5-HT3A and 5HT7 receptors.
Reversible inhibitors of HCV NS3-4A protease
Authors: Patrick Graham L.
Published: September 2023

This chapter discusses boceprevir and telaprevir, which contain a ketoamide group which reacts with the catalytic serine residue of a viral protease enzyme labelled HCV NS3-4A and forms a reversible covalent bond. It looks at several approved reversible inhibitors that bind through intermolecular bonds alone, such as simeprevir. This was the first to reach the market and approved by the FDA in 2013. It also covers some of the research that led to the discovery of the reversible inhibitors. The chapter details the modification of the structure of BILN-2061, which was the first HCV protease inhibitor, that led to simeprevir. It examines binding studies carried out on simeprevir that revealed that the hydrocarbon region of the macrocyclic ring occupies the S1 and S3 subsites and forms several van der Waals interactions with hydrophobic amino acid residues.
Pie charts and tables for qualitative data
Authors: Humphreys Rosalind K. , Ruxton Graeme D.
Published: September 2023

This chapter considers pie charts and tables as a choice of qualitative data presentation. It explains how to produce clear and effective pie charts using nominal data or ordinal data and Word. Pie charts are most likely to be useful with qualitative data in percentage form and data that add up to 100 per cent. Thus, segments of pie charts are most easily interpreted when they either ascend or descend in size order as data move around from the top or they follow the logical ordering of the categories. The chapter discusses the basic code for pie charts when using R.