bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equilibrium dialysis and rate dialysis
Authors: Honoré Bent 
Published: November 2023

Abstract
Studies on the interaction of low molecular mass molecules, i.e. ligands, with high molecular mass protein molecules play fundamental roles in biomedical research. Among important examples to be mentioned are drug binding to plasma proteins, especially albumin (1), vitamins to their transport proteins, as well as binding of various substances, e.g. hormones and transmitter substances to receptor proteins in their target cells. Ideally the questions to be answered from such studies are how many ligand molecules, N, may bind to a given macro molecule and with what affinities, K1, K2, .. , KN under the given set of conditions specified by, e.g. pH, temperature, ionic strength, and buffer composition.
Protein-ligand interactions studied by FTIR spectroscopy: methodological aspects
Authors: Jackson Michael , Mantsch Henry H 
Published: November 2023

Abstract
Many techniques exist for the study of protein-ligand interactions, with each technique providing unique and/or complementary information. For example, calorimetric studies provide information relating to the energetics of protein-ligand interaction (Volume 1, Chapters 10 and 11), while X-ray diffraction techniques provide information on the molecular cordinates of atoms in the protein-ligand complex (see Chapter 1). Between these extremes lies a bewildering array of methods varying in technical sophistication, cost, and information content.
Electrospray ionization mass spectrometry
Authors: Hill T J , Derrick P J 
Published: November 2023

Abstract
Characterization of protein-ligand interactions involves the determination of stoichiometry, affinity, and conformational changes associated with such interactions. Mass spectrometry is rapidly emerging as an important and powerful new tool in this area to complement the wealth of other techniques described in these volumes. The development of ionization methods, such as electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI), applicable to biomolecules in solution or as solids has allowed the routine analysis, with picomole (10™12 M) to attomole (10™18 M) sensitivity, of proteins, peptides, oligonucleotides, carbohydrates, and other classes of biomolecule. Extending beyond simple molecular mass determinations, mass spectrometry is now readily applied to the sequencing of peptides, proteins, and DNA as well as for the study of protein aggregation, folding, and non-covalent interactions in general.
NMR studies of protein-ligand interactions
Authors: Lian Lu-Yun 
Published: November 2023

Abstract
The interactions between pairs of molecules are crucial in many molecular recognition processes in biology, the main examples being found in complexes of proteins with other proteins (e.g. in signalling processes), with small molecules (e.g. enzyme-substrate or protein-drug interactions), and with nucleic acids (e.g. protein-RNA complexes, transcription factors with DNA). Like many other bio-physical techniques, nuclear magnetic resonance (NMR) provides information about protein-ligand interactions. However, unlike many of the other techniques such a fluorescence spectroscopy, isothermal titration calorimetry, and surface plasmon resonance, NMR provides information on many different aspects of these interactions, ranging from structures to dynamics, kinetics and thermodynamics. Recent developments in NMR technology (1, 2), together with the routine use of stable isotopes (13C,15N,2H), have enabled the use of a much greater variety of NMR-based techniques for studying protein-ligand interactions, and involving much larger protein systems; these techniques have been used in a many different basic and applied research environments (3, 4). Examples of the latter are evident, for example, in the use of NMR as a method for high-throughput screening in drug development programmes in the pharmaceutical industry (5-7).
Quantification and mapping of protein-ligand interactions at the single molecule level by atomic force microscopy
Authors: Roberts Clive J , Allen Stephanie , Davies Martyn C , Tendler Saul J B , Williams Philip M 
Published: November 2023

Abstract
This chapter illustrates the recent application of atomic force microscopy (AFM) to the measurement of the forces that bind protein-ligand complexes. The experiments highlighted will demonstrate the potential of AFM to quantify the adhesion force between individual molecular pairs and how this can lead to a deeper understanding of protein structure and function. The possibility of spatial mapping active surface bound proteins though their ability to bind ligands will also be illustrated.
An understanding of the recognition mechanisms is not only of importance in understanding protein structure, folding, and function but has practical implications for the development of novel devices in areas such as sensors, screening, and drug discovery.
Molecular basis of integrin-dependent cell adhesion
Authors: Humphries Martin J , Liddington Robert C 
Published: November 2023

Abstract
The integrins are a family of heterodimeric (α β) plasma membrane proteins that bind the extracellular matrix or counter-receptors on other cells (1). They transduce bidirectional signals across the plasma membrane that are critical to many biological processes, including embryonic cell migration, wound healing, and the immune response. In pathogenic states they play an essential role in tumour metastasis and angiogenesis. The adhesiveness of integrins’ extracellular domains is allosterically controlled by binding events in their cytoplasmic domains that trigger conformational changes across the plasma membrane (‘inside-out’ signalling). Under some conditions it is ligand binding to the extracellular domains that triggers an intracellular signal (‘outside-in’ signalling). There are two mechanisms by which integrins could change the adhesiveness of cells, which are not necessarily exclusive. ‘Affinity’ changes caused by conformational changes in individual integrin molecules are believed to be responsible for both the initial rapid and reversible change in the affinity of platelets for damaged blood vessels and of leucocytes for sites of inflammation (2). ‘Avidity’ changes brought about by the synergistic effect of multiple clustered integrins on the cell surface binding to clustered or polyvalent ligands are thought to play a role in the stable attachment of cells to the extracellular matrix (ECM) (3).
The cell cycle
Authors: Tyers Mike , Jorgensen Paul 
Published: November 2023

Abstract
The accurate replication and segregation of the genome during cell division is orchestrated by the cyclin-dependent protein kinases (CDKs) and their attendant regulatory partners, the cyclins and CDK inhibitors. At its most fundamental level, the cell division machinery is programmed by a state of low CDK activity in GI phase and a state of high CDK activity in S, G2 and M phase. These two states dictate the once and only once replication and segregation of the genome per division cycle. Thus, low CDK activity triggers exit from mitosis and the establishment of competent origins of DNA replication, whereas high CDK activity activates firing of prereplicative origins, prevents the refiring of spent origins and catalyses entry into mitosis. The alternation between the two CDK states is controlled by a switch that is flipped once in each direction per cell cycle. In late G1 phase, CDK activity is switched on while in late mitosis it is switched off. This switch is constructed from three major elements: CDK-dependent phosphorylation, cell cycle-regulated waves of transcription, and ubiquitin-dependent proteolysis of key regulatory proteins. In this chapter, we describe the mechanisms that generate the fundamental oscillation in CDK activity that lies at the heart of the cell cycle in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe.
The structure of yeast centromeres and telomeres and the role of silent heterochromatin
Authors: Pidoux Alison L , Allshire Robin C 
Published: November 2023

Abstract
Genome stability and accurate chromosome segregation are of paramount importance to the cell and to the organism. The consequences of mistakes in mitosis and meiosis are severe indeed. In unicellular eukaryotes, aneuploidy is often deleterious or even fatal. For complex eukaryotes, chromosome gain or loss events are a leading cause of genetic diseases, miscarriage, and birth defects, and contribute to the progression of cancer. Chromosome rearrangements and fusions resulting from free DNA ends (e.g. those lacking telomeres) may have profoundly deleterious effects. To ensure their structural integrity and successful transmission, chromosomes must have origin(s) of replication, a single functional centromere and, if linear, telomeres.
The centromere was originally defined cytologically on mammalian chromosomes as the site of the primary constriction. Together with its associated proteinaceous kinetochore, this region of DNA is responsible for chromosome attachment to spindle microtubules and chromosome segregation at cell division (1). Centromcres perform very precise functions; during the S phase of the cell cycle, chromosomes are replicated, but the two chromatids must remain associated at their centromere until mitosis. At the onset of mitosis, sister kinetochores must specifically bind to microtubules emanating from the two opposite poles of the spindle. When all chromosomes are correctly attached and oriented on the metaphase plate, the sister chromatids part company and move to the spindle poles in anaphase, led by their kinetochores. In meiosis the situation is more complex.
Cell labelling and transplantation techniques
Authors: Kane Donald A , Kishimoto Yasuyuki 
Published: November 2023

Abstract
What with their genetics, zebrafish have become the Drosophila of the vertebrates. But these little fish have many other advantages. As the developmental biologists of the mid-twentieth century knew (1), zebrafish are superb for observational studies of development. Their eggs are fertilized externally, so that it is a simple matter to have the embryos on a compound microscope a few moments after fertilization. There, the transparent embryo reveals the early cell cleavages of the blastula, the cell movements of the gastrula, or, later, the forming internal organs of the larva. In situ hybridization and antibody reactions are done as whole mounts, for sectioning can be done later, if at all. And if lineage tracer is injected into cells, as we describe in this chapter, the cells can be recorded for days, and sometimes weeks, afterwards. The technique of moving about pieces of tissue from embryo to embryo has been an essential part of developmental biology for nearly a century. By placing developing cells into ectopic positions, we test the potential of the transplanted cells to develop into fates appropriate for the new position. These techniques, described in this chapter, are essential for connecting the developmental biology of the zebrafish to that of more traditional experimental vertebrates, such as Xenopus and chick, and are also necessary for the analysis of gene action in the zebrafish mutants.
Speculations on the origin and evolution of editing
Authors: Gray Michael W 
Published: November 2023

Abstract
The discovery of RNA editing quickly prompted three evolutionary-type questions: how did it evolve, why and when? In many cases, RNA editing appears to fix a problem in genetic information transfer. In mRNA, coding regions are brought into frame (1) or even created de novo (2, 3), codons are changed so they specify phylo genetically conserved amino acids (4, 5) and initiation and termination codons are formed (4, 6–14). The result is a translatable mRNA that codes for a functional protein, one that could not have been made in the absence of editing. In non-coding RNAs (rRNA and tRNA), missing primary and/or secondary structural motifs are restored, again creating a functional RNA from a non-functional transcript (15–17). In certain instances, intron sequences must be edited to produce a splicing-competent structure (18). Because of these characteristics, RNA editing systems have often been regarded as having an RNA repair function, with this role serving as their evolutionary raison d’être.
Risk Assessments For The Use Of Radioisotopes In Biology
Authors: Ballance Peter E 
Published: November 2023

Abstract
Ever since the early 1950s when radioisotopes began to be used extensively in experimental biology, research group leaders, supervisors and individual researchers instinctively asked themselves what were the hazards from the radioactive materials to be used, what were the risks to health and how these risks should be minimized. In the process of selecting radioisotopes for particular experiments, research workers needed to obtain detailed information on the way radioisotopes decayed. In order to use radioisotopes as tracers for specific elements or compounds in biological systems, they needed to know whether charged particles or electromagnetic radiation (or both) were emitted, and hence how to determine the best choice of radiation detection equipment to be used. From the physical data available they were able to gain some insight into the likely hazards which would be associated with the presence of the radioactive elements. With the well documented knowledge of the effects of ionizing radiation on living organisms, particularly the effects of atomic weapons, they instinctively sought to assess the risks to their health and, in turn, to take steps to minimize these risks.
Radioisotope Detection Using X-Ray Film
Authors: Laskey Ron A 
Published: November 2023

Abstract
During the last three decades gel electrophoresis has steadily replaced other methods for analytical fractionation of macromolecules. This chapter describes and discusses methods of detecting radioisotopes within flat samples such as accylamide or agarose gels, nitrocellulose filters, thin layer chromatography plates and paper chromatograms. For all of these samples X-ray film provides a convenient non-destructive means of isotope detection which combines high sensitivity with high resolution. Alternative storage phosphor technology is described in Chapter 5. Autoradiography of microscopy slides is described in Chapter 9.
In vitro Labelling Of Nucleic Acids And Proteins
Authors: Cunningham M W , Patel A , Simmonds A C , Williams D 
Published: November 2023

Abstract
Radioactive tracers are uniquely suited for the labelling of biological molecules because their presence generally has no effect on the properties of those molecules. Indeed, most of the radioisotopes used can be incorporated into biomolecules in place of the equivalent non-radioactive element. This is particularly important when the biomolecule is itself being used as an enzyme substrate since enzymes tend to display a strong selectivity for their specific substrates.
Summary Of Legislation In Radiological Protection In The UK
Authors: Prime David , Frith Barry 
Published: November 2023

Abstract
The use of equipment or materials that emit radiations is governed by two pieces of legislation-the Radioactive Substances Act (1993) and the Ionising Radiations Regulations (1999). This legislation imposes a system of radiological protection that is almost the same in all premises using radioactive materials or radiation-emitting equipment. This system will be outlined in two sections dealing with the respective items of legislation.
Probing G protein-coupled receptors by fluorescence spectroscopy
Authors: Turcatti Gerardo 
Published: November 2023

Abstract
The broad development of approaches based on fluorescence detection in receptor research in recent years can be seen as a consequence of two main scientific advances. First, is the development and optimization of systems for the overexpression ofreceptors (1) that started early in the 1990s. Classic fluorescent techniques, that were not sensitive enough to detect receptors from natural sources or poorly expressed recombinant receptors, became available for this purpose with the important advantage of several years of experimentation behind them. Secondly, are the methodological and instrumental improvements in the sensitivity of fluorescence measurements that can now detect single molecules (for a review see ref. 2).
From receptor to endogenous ligand
Authors: Nothacker Hans-Peter , Reinscheid Rainer K , Civelli Olivier 
Published: November 2023

Abstract
Homology screening and advances in the human genome project have spawned an explosion in the field ofG protein-coupled receptors (GPCRs) resulting in the discovery of hundreds of new ones. A large number of these bind unknown natural ligands and are called ‘orphan’ GPCRs. The major challenge lies in the discovery of their functions, defining their physiological roles, and possibly their therapeutic potentials. The key to this daunting task lies in the identification of the natural endogenous ligand(s) that bind to and activate the orphan GPCRs. These ligands can then be used in behavioural assays to attempt to define the functional role of the orphan receptor systems. They can also be used to develop specific agonists and antagonists ultimately to provide therapeutic drugs.
Monitoring nuclear receptor function
Authors: Nunez B Scott , Vedeckis Wayne V 
Published: November 2023

Abstract
The glucocorticoid receptor (GR), one of the first nuclear receptors to be characterized and to have its gene cloned, serves to illustrate the complexity of nuclear receptor function. The expression of the GR gene is regulated by at least three different promoters and the resulting mRNAs can be differentially spliced into several transcriptional variants (1-3). Following the translation of these transcripts into protein, the activity and/or subcellular distribution of the GR protein may be modified by post-translational modifications such as phosphorylation (4). In the absence of ligand, the GR is found primarily in the cytoplasm associated with protein chaperones, such as heat shock protein 90 (HSP 90), which act to maintain the receptor in an inactive state (5). Other proteins, called co-activators and co-repressors, bind to and modulate the transcriptional activity of nuclear receptors (6). The GR is activated by binding glucocorticoid (GC): it is then translocated into the nucleus where it can alter gene transcription through two avenues. The classical mode of action is for activated GR to alter transcription directly by binding a glucocorticoid responsive element (GRE), a negative glucocorticoid responsive element (NGRE), or a composite GRE. The GR can also alter transcription directly without binding DNA by interacting with other transcription factors that bind DNA. The second avenue of GR action is via transcriptional interference, whereby the activity of a transcription factor is diminished by an interaction with the GR (7).
Sequence databases and analysis sites
Authors: Apweiler Rolf , Lopez Rodrigo 
Published: November 2023

Abstract
EMBL Outstation, The European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UK. Recent years have seen an explosive growth in biological data, which is often not published anymore in a conventional sense, but deposited in a database. Sequence data from mega-sequencing projects may not even be linked to a conventional publication. This trend and the need for computational analyses of the data make databases and database search tools essential for biological research.
Agricultural biotechnology
Authors: Carollo Victoria 
Published: November 2023

Abstract
It is widely agreed that humans made the transition from a nomadic huntergatherer lifestyle to one dependant largely on agriculture about 10,000 years ago in the Pre-Pottery Neolithic Near East. Archeological evidence of the Neolithic founder crops (einkorn wheat, emmer wheat, barley, lentil, pea, bitter vetch, chickpea, and flax) has been traced to a small area within the ‘Fertile Crescent’ near the upper Tigris and Euphrates rivers in what today is southeast Turkey and northern Syria (1).
Internet collaboration
Authors: Atherton David , Lau Chin Hoon , Kondu Pinar , Gore-Langton Robert E , Leifer Zev 
Published: November 2023

Abstract
This chapter surveys the types of technologies, applications, and organizational approaches that best support the needs of scientific collaboration. Although briefly covering the foundations of internet communications technologies, such as e-mail and newsgroups, emphasis has been placed on solutions to support real-time interactions and shared tools since we believe these provide the greatest opportunities for meaningful collaboration. Some of these tools also provide the greatest technological challenges, but the rewards in terms of creativity and efficiency are often worth the effort.
A Longitudinal Study of Gaming Patterns During the First 11 Months of the COVID-19 Pandemic
Authors: Ritchie Emma V. , Rapinda Karli , Wardell Jeffrey D. , Kim Hyoun S. , Keough Matthew T. 
Published: November 2023

ABSTRACT

Objectives:
The objective of this study was to longitudinally study engagement in video gaming throughout the first 11 months of the COVID-19 pandemic using latent growth curve modeling.

Methods:
A total of 332 Canadian adults (M
age=33.79, 60.8% men) who played video games were recruited from the crowdsourcing site Prolific. Participants responded to 4 waves of surveys (spaced 3 mo apart) from April 2020 to March 2021. The main outcome of interest was time spent gaming, measured in hours spent gaming in the past 30 days before each assessment wave.

Results:
Latent growth curve modelling showed that participants reported high initial levels of gaming, but progressively declined in gaming activity across the subsequent waves. Being male, living with others, experiencing a decrease in income because of COVID-19, endorsement of disordered gaming symptoms, game preference, and solitary gaming were significant predictors of increased gaming at the outset of the pandemic. However, only age was related to longer-term declines in gaming during the pandemic, such that older participants’ gaming decreased at a more accelerated rate.

Conclusions:
This study suggests that gaming declined over the course of the pandemic and was not a problematic behaviour on average among a community sample of Canadian adults during the COVID-19 pandemic.

Objectifs:
L’objectif de cette étude était d'étudier longitudinalement l’engagement dans les jeux vidéo au cours des onze premiers mois de la pandémie de COVID-19 en utilisant la modélisation de la courbe de croissance latente.

Méthodes:
Au total, 332 adultes canadiens (âge=33,79, 60,8% d’hommes) jouant à des jeux vidéo ont été recrutés sur le site de recrutement Prolific. Les participants ont répondu à quatre vagues d’enquêtes (espacées de 3 mois) d’avril 2020 à mars 2021. Le principal résultat d’intérêt était le temps passé à jouer, mesuré en heures passées à jouer au cours des 30 derniers jours précédant chaque vague d'évaluation.

Résultats:
La modélisation de la courbe de croissance latente a montré que les participants ont signalé des niveaux initiaux élevés de jeu, mais ont progressivement diminué leur activité de jeu au cours des vagues suivantes. Le fait d'être un homme, de vivre avec d’autres personnes, de subir une baisse de revenu en raison du COVID-19, d’endosser des symptômes de troubles du jeu, les préférences de jeux et de jouer en solitaire étaient des facteurs prédictifs significatifs d’une augmentation de l’activité de jeu au début de la pandémie. Cependant, seul l'âge était lié à une diminution à plus long terme du jeu pendant la pandémie, de sorte que le temps de jeu des participants plus âgés diminuait à un rythme plus rapide.

Conclusions:
Cette étude, prise parmi un échantillon communautaire d’adultes canadiens pendant la pandémie de COVID-19, suggère qu’en moyenne, le jeu a diminué au cours de la pandémie et n’a pas été un comportement problématique.