bluuebunny/crossref_metadata_2025_split huggingface dataset:
An introduction to the nerve tertninal
Authors: Kelly Regis b. 
Published: November 2023

Abstract
Synaptic transmission between nerve cells can usefully be viewed as a specialized example of cell-to-cell communication. A cell in a metazoan organism communicates most simply by releasing a signal which diffuses until it is detected by receptors on a neighbouring cell, a process called paracrine communication. If the signalling cell is very far away from the target cell simple diffusion will not work. In such cases the signalling cells can release the signal into the bloodstream, which carries it by the blood flow into the vicinity of the target cell. This is called endocrine communication. We can immediately see the problem facing an endocrine signalling cell. If enough signal is to reach the target, the endocrine cell must release into the body vast quantities of signal compared with what is needed for paracrine signalling. This requirement is reflected in the morphology of endocrine cells. Their cytoplasm is packed with secretory vesicles that contain the signalling molecule at concentrations approaching those that cause crystallization.
Neurotransmitter transporters
Authors: Krantz Davide , Chaudhry farrukh A , Edwards Robert H 
Published: November 2023

Abstract
Synaptic transmission involves two distinct types of neurotransmitter transport activity. Plasma membrane reuptake is generally considered to terminate the action of neurotransmitter in the extracellular space. Transport from the cytoplasm into secretory vesicles packages transmitter for regulated release by exocytosis. Although the two activities thus have important if not essential roles in synaptic transmission, the mechanisms of active transport, their regulation and roles in signalling remain poorly understood. Molecular analysis has also suggested previously unanticipated functions for plasma membrane and vesicular neurotransmitter transporters.
Studying mutants that affect neurotranstnitter release in C.elegans
Authors: Nonet Michael L 
Published: November 2023

Abstract
Sydney Brenner initiated the study of the nematode Caenorhabditis elegans in the early 1960s with the specific intent of developing the organism as a model to study the nervous system. Primarily through the isolation and characterization of mutants that disrupt the functioning of the nervous system at the behavioural level, studies of the nematode have contributed to our understanding of the molecular mechanisms underlying a wide variety of neuronal processes including axonal outgrowth (1), sensory reception (2, 3), and synaptic transmission (4). The strength of the nematode as a model organism is undoubtedly the ability to apply powerful genetics to a biological problem. However, in the long-term, the dissection of the role of molecules in a complex process such as synaptic transmission requires the synthesis of results obtained using a variety of experimental approaches. Here, I first review the approaches available in C. elegans which have been utilized to characterize the molecules underlying the regulated release of neurotransmitter. Subsequently, I examine the complexity of the synaptic transmission apparatus in C. elegans through a discussion of mutants in a variety of genes which perturb the process. Finally, I discuss the avenues of research where the study of C. elegans is most likely to provide future insight that is applicable to understanding the machinery operating at synapses in all organisms.
Laboratory computing in medical microbiology
Authors: Lovering Andrew M 
Published: November 2023

Abstract
There can be few, if any, clinical microbiology laboratories in the UK that are without some form of computer system. Indeed. many laboratories will be running their second, or even, third generation of system and most will be acutely aware of the relative advantages and disadvantages of a laboratory computer system. Consequently this chapter will not address the basic principles and methods of operation of microbiology laboratory computer systems, as these will be familiar to most readers, but highlight some of the developing issues in Information Technology (IT) that are impacting on microbiology laboratories. For those readers unfamiliar with such basic principals the chapter by MacGowan et al. (1) and the paper by Kenny (2) are strongly recommended.
The nature and significance of protein folding
Authors: Dobson Christopher M , Kiefhaber Thomas 
Published: November 2023

Abstract
Proteins are involved in virtually every biological process in a living system. They are synthesized on ribosomes as linear chains of typically several hundred amino acid residues in a specific order from information encoded within the cellular DNA. In order to function, it is necessary for these chains to fold into the unique, native, three-dimensional structures that are characteristic of the individual proteins. It is clear that this folding process can take place rapidly.
Kinetic models in protein folding
Authors: Bieri Oliver , Kiefhaber Thomas 
Published: November 2023

Abstract
Experimental work on the mechanism of protein folding has been greatly influenced by Levinthal’s famous paper of 1969 (1), in which he pointed out that a polypeptide chain would require an astronomical time to explore at random all possible con formations in order to finally reach the native state. This motivated the search for partially folded intermediates guiding the protein to the native state. Although many proteins have been found to fold through transient intermediates (for reviews see refs 2-10), more recent theoretical studies have sparked off a discussion on their role in the folding process.
The molten globule state: the physical picture and biological significance
Authors: Kuwajima Kunjhjro , Arai Munehito 
Published: November 2023

Abstract
According to a classic view of protein folding, there is a specific folding pathway on which a protein has to go through a sequence of conformational intermediates in order to fold into the native structure. For this reason, studies on protein folding have been focused on the detection and characterization of folding intermediates (1) and, in particular, the molten globule state, which has been regarded as a general inter mediate of protein folding (2–4).
Protein folding and import into organelles
Authors: Rassow Joachim 
Published: November 2023

Abstract
How do proteins find their distinct functional location within the cell after they have been synthesized? In the last 15 years this basic biological question has opened a new field of molecular cell biology. The sites of protein synthesis and function are often separated by membranes. Therefore, the structures and mechanisms which drive proteins across membranes are of fundamental importance in the correct distribution of newly synthesized proteins in the cell (1). In this chapter, several of the techniques will be described which are applied to characterize intracellular protein traffic. All the protocols involved are easy to perform and do not require special equipment so they can be readily adopted by non-specialists. More sophisticated protocols can be obtained from the literature cited in the references.
Functional significance of O-GlcNAc glycoproteins in the nucleus and cytoplasm
Authors: Kreppel Lisa K , Hart Gerald W 
Published: November 2023

Abstract
O-GlcNAcylation is a form of intracellular protein glycoslyation consisting of a single N-acetylglucosamine residue [3-O-linked (O-GlcNAc) to the hydroxyl group of serine and threonine. Unlike other carbohydrate modifications, O-GlcNAc is not elongated to more complex structures and is found almost exclusively in the nucleus and cytoplasm (1, 2). O-GlcNAc-modified proteins are found in virtually all eukaryotic organisms, but not in bacteria (3, 4). Studies have demonstrated that the O-GlcNAc modification is dynamic and abundant, exhibiting characteristics more like phosphorylation than typical N-and O-linked glycosylation (5-8). Increasing evidence suggests that O-GlcNAc is a regulatory modification that may modulate numerous biological processes.
Molecular differentiation of bacterial strains
Authors: Brown Eric W 
Published: November 2023

Abstract
Understanding the epidemiological principles that govern bacterial populations has become paramount in the fields of medical, environmental, and agricultural microbiology (1). The introduction of bacterial strains which exhibit more aggressive and deadly pathological phenotypes, development of multi-drug antibiotic resistance, and acquisition of novel modes of transmission between host organisms has placed a renewed pressure on researchers to be able to identify and monitor the origins and dissemination of destructive genetic variants (strains) within a species. It has become apparent that the best approaches to characterizing individual strains are founded in the practical application of molecular biology. Molecular genetic techniques such as polymerase chain reaction (PCR), nucleic acid fingerprinting, and DNA sequence analysis of the bacterial chromo-some have allowed for remarkable advances in bacterial identification as in many other areas of microbiology (2). Whether the need for molecular typing involves the tracking of nosocomial (hospital-borne) outbreaks, identifying the reservoirs of food-borne infections, or the discrimination of plant pathogenic strains in the field, the isolation of a specific genotype in conjunction with a specific bacteria often allows for a larger understanding of the epidemiological principles that govern the evolution and spread of many bacterial diseases.
Evolutionary analysis of molecular sequence data
Authors: Hughes Austin L , Silva Jack da , Verra Federica 
Published: November 2023

Abstract
In the 140 years since Darwin’s Origin of Species was published, evolutionary ideas have formed an important part of the theoretical framework of biological research, but their practical consequences have been few for most of that period. The situation has changed since the advent of techniques for rapidly sequencing nucleic acids. Because evolution is nothing other than change in nucleotide sequences, the availability of sequence data enables us to study evolution far more directly than was previously possible. Molecular evolutionary analysis has now become an important part of the conceptual arsenal used by biologists in a wide variety of disciplines, including epidemiology.
HLA-peptide tetrameric complexes
Authors: Ogg Grahams. 
Published: November 2023

Abstract
HLA-peptide tetrameric complexes allow the direct visualization of antigen specific T cells by flow cytometry (1-3). Therefore, unlike other techniques used to study antigen-specific T cells, the method is independent of a functional activity such as cytokine production or lysis of target cells. Furthermore, the complexes are sufficiently sensitive (down to 0.02% of CDS+ T cells) to be used directly ex vivo, in contrast to assays of cytolytic function, which usually require a period of expansion in vitro before lysis becomes detectable. HLA-peptide tetrameric complexes are synthesized by the addition of biotin to the inferior aspect of refolded HLA molecules. Streptavidin has four biotin-binding sites and so will induce the formation of tetrameric structures of biotinylated HLA molecules. HLA heavy chain and β2microglobulin ( 2m) are generated in Escherichia coli as inclusion bodies. Only the extracellular portion of the heavy chain is included, and this is modified by the addition of a C-terminal signal sequence containing a site for biotinylation by the bacterial biotin ligase enzyme BirA. The inclusion bodies are solubilized in urea and then added to a refolding reaction along with an epitope peptide. The process of diluting the denaturant urea in the refolding buffer allows a proportion of the HLA heavy chain to refold with β2 and peptide into a conformationally correct form. The complex is then biotinylated at room temperature by the enzyme BirA in the presence of biotin, ATP, and Mg2+. Purification by gel filtration and ion exchange is followed by the addition of fluorescent streptavidin in a 1:4 molar ratio with the refolded complex to generate the tetramers. A tetrameric structure overcomes the low affinity of T-cell receptors (TCRs) for peptide/HLA, which for single complex interactions has an off-rate half-life of 12-30 sec at 25°C (reviewed in ref. 4). In fact, a trimeric structure may be sufficient-trimers and tetramers of a cytochrome c/I-Ek complex were shown to induce intracellular pH changes in specific T cells, whereas monomers and dimers were inactive (4).
Further applications to cell biology
Authors: Ormerod Michael G 
Published: November 2023

Abstract
There are a multitude of applications for flow cytometry, the most important of which have been covered in earlier chapters. In this chapter, five further applications to cell biology are described. The first is a method for estimating cell viability; the second, a way of monitoring the effect of high electric fields on cells; the third, a method for measuring the production of oxidative species in cells; and the last section discusses two methods for characterizing drug resistance in cancer cells, including a method for measuring intracellular glutathione.
Lmmunocytochemistry for light microscopy
Authors: Satiat-Jeunemaitre Beatrice 
Published: November 2023

Abstract
With the near completion of many of the genome sequencing programmes, the discipline of proteomics (the quantitative and physical mapping of cellular proteins and their function) will become one of the dominant topics in biology for the foreseeable future. As part of this, the unravelling of the spatial pattern of protein distribution and other molecular components throughout the cell is essential if we are to fully understand cell function. To provide such information, immunohistochemistry and immunocytochemistry have been increasingly valuable research techniques since they were first introduced in the late 60s.
The roles of the major cytoplasmic chaperones in normal eukaryotic growth: Hsc70 and its cofactors
Authors: Pfund Christine , Yan Wei , Craig Elizabeth A 
Published: November 2023

Abstract
The role of chaperones in the prevention of protein aggregation in cells experiencing stress is well established (see Chapters 1 and 9); however, problems of protein misfolding and aggregation are not confined to the stressed cell. Even under optimal growth conditions, there is a need for chaperone action. In the past few years, this aspect of chaperone function has become increasingly obvious as researchers focus their attention on the processes of translation, translocation across membranes, and the assembly/ disassembly of protein complexes. Within the crowded environment of the cell, each protein must be protected from misfolding and aggregation. In this chapter, we discuss the processes in the normal cell that require chaperone assistance and the evidence from studies using eukaryotes that support a role for both Hsp70s and their cohort proteins in these processes.
Laying Down The Vertebrate Body Plan
Authors: Tickle C , Davey M 
Published: November 2023

Abstract
How do different parts of the body arise in their proper positions in vertebrate embryos? In the first chapter, the principles of pattern formation were reviewed. This chapter outlines how the body plan is laid down, and provides the embryological background for the following chapters that deal in detail with patterning of mesoderm (Chapters 3 and 4), nervous system (Chapters 5, 6, 7, and 8), and limbs (Chapter 9) and the molecules involved. Laying down the body plan is essentially a matter of defining the main body axes: the anteroposterior axis (head to tail axis, sometimes known as rostral-caudal axis) and dorsoventral axis (back to front). Once these two axes have been set up, this also defines right and left (Fig. 1). In addition, the three main body layers—ectoderm, mesoderm, and endoderm—are formed and arranged so that endoderm comes to lie on the inside, ectoderm on the outside, and mesoderm in between. Establishment of these layers in their proper positions requires considerable cell rearrangements, which must be precisely choreographed.
Constructing phage display libraries by oligonucleotide- directed mutagenesis
Authors: Sidhu Sachdev S , Weiss Gregory A 
Published: November 2023

Abstract
As with any selection technology, the success of phage display depends on library diversity and quality. This chapter details robust methods that can be used to rapidly construct highly diverse phage-displayed libraries. Our protocols optimize previously described methods, allowing for the facile construction of libraries almost 100-fold greater than previously thought practical (1). Libraries with diversities greater than 10 can be readily constructed with a single reaction, and multiple reactions can be combined to generate libraries with diversities on the order of 10.
Multicolour FISH and spectral karyotyping
Authors: Bayani Jane , Squire Jeremy A 
Published: November 2023

Abstract
It is often difficult to determine the identity of a small structural chromosomal aberration with certainty using conventional cytogenetic banding methods alone. The problems that can typically arise in both clinical and cancer cytogenetics are the presence of structural chromosome aberrations with unidentifiable chromosomal regions, or very complex chromosomes (sometimes called ‘marker chromosomes’) in which no recognizable region appears to be present. Confirmation of the cytogenetic origins of such chromosomal aberrations can sometimes be obtained by the judicious application of locus-specific FISH analysis (see Chapter 9) if the investigator has some general impression regarding a possible identity. However, such an approach is very subjective, risky, and requires some knowledge of the specific loci and available probes likely to be involved in the aberration.
Popular Influence and State Power
Authors: Ginsberg Benjamin 
Published: November 2023

Abstract
Critics of the American political process seldom hesitate to propose remedies for the nation’s supposed political ills. Proponents of new campaign finance rules, lobbying regulations, voting reforms, and the like all seem confident that their nostrums will promote civic virtue and enhance popular influence. Few reformers, however, are sufficiently radical to confront the fundamental problem of citizen influence in political life. To put the matter succinctly, popular influence is inversely related to the state’s power. Weak governments are vulnerable to popular pressure. The more powerful the government and the greater the scope of its activities, the less the chance that it will concern itself with citizens’ views.
Gender And Genome
Authors: Hamilton W D 
Published: November 2023

Abstract
IN his The Genetical Theory of Natural Selection R. A Fisher included a certain passage about sex,ratio selection that after his death became famous among evolutionary biologists. It is a good example of what may be called his slit-trench style-short and deep. Many have fallen into this trench and been slow either to escape or to feel sheltered there, and I was one. Nowadays the trench catches fewer because there are many other good accounts of how selection works on the sex ratio; indeed, I believe that, in a purely qualitative way, the opening passage of my 1967 paper presents Fisher’s idea more clearly than he did. However, by the time I was able to write such a stepwise account, my struggles had revealed to me that there was a lot that Fisher’s argument had not covered. I saw that there were at least two kinds of influence that might affect selection of tendency to produce one sex or the other. First, there is the question of what genetic element is imagined to be controlling the sex ratio, and in which sex and at what stage the element acts. Second, there is the question of whether the population might be grouped such that the all with all (panmictic) competition assumed in Fisher’s argument would not apply.
Discordant Insects
Authors: Hamilton W D 
Published: November 2023

Abstract
Reading about them was not enough, they were too fantastic. Only in 1963 in Brazil did I first thoroughly believe in fig wasps, the tiny black insects that both breed in and pollinate all fig trees. Worldwide this means 600 species, not just the one cultivated species that is most familiar to Northern Europeans for its dried fruits in the brown, oblong packets. The 600 mainly inhabit tropical countries where many are giants of the forest. To this great assemblage the almost shrubby European fig stands an outlier in several ways. For example, besides its geographic placement as the world’s most northerly fig, and its small stature, it is dioecious-that is, has male and female trees separate like holly or yew. Again, generally each fig species has one kind of wasp adapted to pollinate it, but the European can sometimes have none; for the most practical and novel pollination feature of the European fig is that although it has a wasp not all its varieties need it, or at least not for their crops.
Prognostic Significance of Signs of Life in Out-of-Hospital Cardiac Arrest Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation*
Authors: Bunya Naofumi , Ohnishi Hirofumi , Kasai Takehiko , Katayama Yoichi , Kakizaki Ryuichiro , Nara Satoshi , Ijuin Shinichi , Inoue Akihiko , Hifumi Toru , Sakamoto Tetsuya , Kuroda Yasuhiro , Narimatsu Eichi ,   Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan II (SAVE-J II) Study Group
Published: November 2023

OBJECTIVES:
Signs of life (SOLs) during cardiac arrest (gasping, pupillary light reaction, or any form of body movement) are suggested to be associated with favorable neurologic outcomes in out-of-hospital cardiac arrest (OHCA). While data has demonstrated that extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes in cases of refractory cardiac arrest, it is expected that other contributing factors lead to positive outcomes. This study aimed to investigate whether SOL on arrival is associated with neurologic outcomes in patients with OHCA who have undergone ECPR.

DESIGN:
Retrospective multicenter registry study.

SETTING:
Thirty-six facilities participating in the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan II (SAVE-J II).

PATIENTS:
Consecutive patients older than 18 years old who were admitted to the Emergency Department with OHCA between January 1, 2013, and December 31, 2018, and received ECPR.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Patients were classified into two groups according to the presence or absence of SOL on arrival. The primary outcome was a favorable neurologic outcome (Cerebral Performance Category 1 or 2) at discharge. Of the 2157 patients registered in the SAVE-J II database, 1395 met the inclusion criteria, and 250 (17.9%) had SOL upon arrival. Patients with SOL had more favorable neurologic outcomes than those without SOL (38.0% vs. 8.1%; p < 0.001). Multivariate analysis showed that SOL on arrival was independently associated with favorable neurologic outcomes (odds ratio, 5.65 [95% CI, 3.97–8.03]; p < 0.001).

CONCLUSIONS:
SOL on arrival was associated with favorable neurologic outcomes in patients with OHCA undergoing ECPR. In patients considered for ECPR, the presence of SOL on arrival can assist the decision to perform ECPR.