bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nerve terminal membrane trafficking proteins: from discovery to function
Authors: Hazuka Christopher d. , Poletti davide L , Scheller Richard H 
Published: November 2023

Abstract
Release of chemical messengers is the primary means by which neurons communicate with target cells. Chemical neurotransmitters are secreted from the presynaptic nerve terminal, travel across the synaptic cleft, and stimulate receptors on postsynaptic cells in a process termed neurotransmission (1). Initial physiological work demonstrated that neurotransmitter is released in packets or ‘ quanta’, and that each quantum consists of a large number of neurotransmitter molecules (2, 3). Ultrastructural studies indicated that a major feature of the presynaptic nerve terminal is a local concentration of uniformly-sized lipid-bound vesicles, promoting the hypothesis that a quantum of neurotransmitter is stored in a vesicle (4). Subsequently, abundant research demonstrated the primacy of these vesicular structures in neurotransmitter release (5, 6). As each vesicle contains a quantum of neurotransmitter, exquisite control of nervous system communication can result from modulation of the behaviour of synaptic vesicles.
The role of phospholipids in neurosecretion
Authors: Martin Thomas F J 
Published: November 2023

Abstract
As emphasized elsewhere in this volume, the function of the nervous system depends upon chemical communication mediated by extracellular signals such as neurotransmitters, neuropeptides, and neurotrophins. The regulated release of these signals into the extracellular space as well as the responses elicited in cells by these signals depends upon integrated molecular events that are membrane based. Neurotransmitter release requires the fusion of secretory vesicles with the plasma membrane whereas regulation by transmitters is mediated by cell surface transmembrane receptors and associated signal transduction complexes. Research on understanding the molecular mechanisms that underlie these processes has understandably focused on identifying key protein participants that operate within or on membrane bilayers. In contrast, the membrane itself has frequently been regarded as a relatively inert platform upon which protein-protein interactions occur. Research over the last 20 years has, however, progressively revealed a dynamic set of regulatory events that involves membrane phospholipids, in particular the inositol phospholipids. These highly phosphorylated lipids exhibit high rates of turnover, and function both as precursors for intracellular messengers as well as key regulators of protein recruitment to and protein function within the membrane. This chapter provides an overview of the multiple roles of inositol phospholipids in neural cell function.
Functional studies of presynaptic proteins at the squid giant synapse
Authors: Burns Marie E , Augustine George J 
Published: November 2023

Abstract
The work of Katz (1) and colleagues established that synaptic transmission arises from the secretion of quantal packets of neurotransmitter from the presynaptic terminals of neurons. More recent work has revealed that release of neurotransmitters is due to the influx of calcium ions into presynaptic terminals and the subsequent localized elevation of calcium concentration within these terminals (2). This rise in presynaptic calcium concentration triggers the fusion of synaptic vesicles with the presynaptic plasma membrane and results in exocytotic discharge of the neurotransmitters stored within the vesicles (3). Exocytosis is only one reaction in a series of synaptic vesicle trafficking events that leads to the local recycling of vesicle components within the presynaptic terminal (see Chapter 1).
Genetic analysis of neurotranstnitter release in tnice and humans
Authors: Lloyd Thomas E , Bellen Hugo J 
Published: November 2023

Abstract
While organisms such as C. elegans, Drosophila, and squid are excellent model systems for studying the fundamental principles of neurotransmitter release in vivo, one of the ultimate goals of these studies is to understand the mechanisms underlying neurotransmitter release in humans. In this respect, the use of invertebrate model systems is validated by the observation that most proteins and processes implicated in synaptic transmission are highly conserved between invertebrates and vertebrates. However, the simplicity of invertebrate model systems does not substitute for the complexity of vertebrate systems, as many sophisticated physiological paradigms and behavioural analyses can only be performed in complex systems such as mice. These studies may provide clues into not only the normal function of genes, but also the role these genes may play in human behaviour and disease. Thus, given the similarities between the mouse and human nervous system, a reverse genetic approach using knock-out technology in mice is at present, and will continue in the foreseeable future, to be one of the most valuable ways to define the function of proteins that are putatively involved in neurotransmitter release in humans.
On the road to destruction: suppression of protein tyrosine kinase signalling by SOCS family proteins
Authors: Rottapel Robert , Ilangumaran Subburaj , De Sepulveda Paulo 
Published: November 2023

Abstract
The complexity of multicellular organisms established during embryogenesis and maintained during adult life relies on the continuous processing of diverse micro environmental signals by various cell types. These environmental signals are often elaborated in the form of membrane-bound or soluble-peptide ligands that bind to cognate cell-surface receptors. One mechanism of transducing signals across the plasma membrane is to couple ligand-induced oligomerization of cell-surface receptors to the activation of protein tyrosine kinases (PTKs). Growth factor peptides such as insulin, epidermal growth factor, and steel factor bind to a class of transmembrane receptors with intrinsic protein tyrosine kinase activity (RTK). On the other hand, cytokines involved in inflammatory, antiviral, or hormonal growth responses bind to a class of receptors which are non-covalently linked to the cytoplasmic, non-receptor protein tyrosine kinases of the Janus kinase (JAK) family. PTK activation provokes intracellular signal amplification and diversification following covalent modification of a wide number of protein targets by tyrosine phosphorylation. Tyrosine phosphorylation modifies enzymatic activity, induces multimeric protein assembly through the recruitment of SH2-containing proteins, and relocalizes signalling molecules to sub cellular compartments where they exert their function. Cytokine receptors activate a complex network of downstream signalling pathways which mediate a diversity of biological responses including cell survival, proliferation, differentiation, and chemo taxis. The initiation and termination of cytokine-induced signalling is tightly regulated. Many mechanisms have evolved to terminate signalling events following receptor activation.
Mechanisms and biology of signalling by serine/threonine kinase receptors for the TGFP superfamily
Authors: Klüoppel Michael , Hoodless Pamela A , Wrana Jeffrey L , attisano Liliana 
Published: November 2023

Abstract
In a multicellular organism, communication between cells and their environment is of fundamental importance for all developmental and physiological processes. This communication relies on the transfer of information from one cell to another through specific signalling molecules. From worms to fruit flies to mammals, the transforming growth factor J3 (TGFJ3) superfamily of growth factors represents a family of signal ling molecules that is of critical importance for a diverse array of biological processes. Here, we will review the current state of knowledge of TGFJ3 signalling, with special emphasis on the recent advances in our understanding of the intracellular mechanisms that transmit TGFJ3-like signals from the cell surface to the nucleus. In addition, we provide an overview of the involvement of TGFJ3 signalling pathways in development and disease.
Folding events in the submillisecond range
Authors: Gruebele Martin 
Published: November 2023

Abstract
Until quite recently, experimental studies of the dynamics of protein folding have been limited to a time resolution of approximately 2 milliseconds. Folding has been induced by stopped-flow mixing (as distinguished from ‘ultra-rapid’ mixing) and the subsequent reactions monitored by a number of traditional spectroscopic probes. A remarkable feature of the folding of many globular proteins observed by stopped flow methods is the presence of submillisecond burst phases (l; Chapter 3). Within this very short timescale, some proteins acquire more than 60% of their secondary structure as measured by CD (Fig. 1). At the same time, ANS binding shows that they can compact to states that may be classified as molten globules, form some well-defined tertiary interactions that can be native or non-native, or remain in a relatively extended conformational ensemble, depending on the folding conditions (2, 3; Chapter 6).
Band T-cell hybridomas
Authors: Bastin Judy m. 
Published: November 2023

Abstract
In 1975, Kohler and Milstein (1) described details of a powerful method in which B cells secreting antibody of one specificity could be fused with a continuously growing plasmacytoma. The fusion product is called a hybridoma, and it will express the immunoglobulin genes from both the normal antibody forming B cell and the plasmacytoma. It will inherit the potential for unlimited growth from the continuously growing plasmacytoma parent and the genetic material determining a given antibody specificity from the antibody secreting parent. The methods used to generate T-cell hybridomas are essentially the same as for B-cell hybridomas, and in 1978 Kontiainen et al. (2) and Taniguchi and Miller (3) isolated the first T-cell hybrid clones. Antigen specific normal T cells are fused to a T-cell tumour line.
Human cytotoxic T-lymphocyte (CTL) studies
Authors: Rowland-jones Sarah L 
Published: November 2023

Abstract
Cytotoxic T-lymphocytes (CTLs) play a major part in the cellular immune response to viruses and other intracellular infections, and in the control of many tumours. They are able to recognize cells expressing foreign antigens through a specific interaction of their T-cell receptors (TCRs) with surface class-I HLA molecules on the target cells which have bound peptides from the pathogen or tumour antigens. This leads to the release of cytokines such as interferon-gamma (IFN--y) and tumour necrosis factor-alpha (TNF-a), chemokines such as RANTES and MIP-la, and ultimately to the lysis of the target cell. The lytic process is caused both by the release of perforin and through fas-ligand triggering of programmed cell-death in cells expressing fas (reviewed in ref. 1). On first contact with antigen the CTLs, which initially expand, can persist as memory cells: in most studies of human CTLs, the aim is to detect and expand in vitro this memory-cell population from peripheral blood mononuclear cells (PBMCs).
Limiting dilution analysis for the quantitation of antigen-specific T cells
Authors: Carmichael Andrew 
Published: November 2023

Abstract
To quantify the number of lymphocytes that have a defined functional property (e.g. antigen-specific cytotoxicity) within a mixed population of cells, one needs an assay that is capable of detecting the presence of a single responding cell. Because the cytotoxic activity of an individual T cell is too small to be measured accurately with existing methods, it is necessary to amplify the response by stimulating the single responding cell to undergo clonal proliferation in vitro to generate a sufficiently large population of daughter cells for their combined cytotoxic activity to be detected. Such an assay therefore measures the number of functional precursor cells that are capable of undergoing clonal proliferation and differentiation into effector cells; if for any reason the function of the cells is impaired so that they are incapable of clonal expansion in vitro, the presence of such cells will be underestimated.
Biochemical characterization of lymphocyte surface antigens
Authors: symons Antony , Brown marion h. 
Published: November 2023

Abstract
The approach taken by cellular immunologists to characterize a lymphocyte surface antigen usually begins with the antibody. In many cases the antibody has been raised by immunization with whole cells, that is against the native molecule on the cell surface. If, on the other hand, the characterization of a lymphocyte surface antigen is approached from information about its DNA sequence, the antibody will most probably have been raised against a recombinant protein or a synthetic peptide.
Thymic organ culture
Authors: Owen John j. T , Mcloughlin deirdre e. J 
Published: November 2023

Abstract
The maturation of T lymphocytes in the thymus is a complex process involving a number of distinct molecular events. Initially, stem cells migrate from the blood into the epithelial thymic primordium (1). These stem cells then undergo a process of T-cell receptor gene rearrangement resulting in the production of separate populations of αβ and γ δ T cells (reviewed in ref. 2). The development of α β T cells is preceded by expression of the pre T-cell receptor which controls the maturational process (3). In addition, differentiation of α β T cells is accompanied by expression of CD4 and CDS antigens. CD4+ CDS+ thymocytes then undergo a rigorous selection process involving the positive selection of cells with ‘useful’ T-cell receptors capable of recognizing foreign antigens in ‘self’ MHC, but negative selection of cells with ‘harmful’ receptors capable of autoreactivity (4).
lmmunofluorescence of surface markers
Authors: Loken Michael R , Green Cherie L , Wells Denise A 
Published: November 2023

Abstract
The discovery of monoclonal antibodies by Kohler and Milstein in 1975 dramatically enhanced the use of immunofluorescence for identifying cell-surface antigens. When applied in the flow cytometric analysis of heterogeneous populations, these highly specific monoclonal antibodies have broadened our understanding of diseases such as the progression of HIV infection, the origin and nature of leukaemia and lymphoma, and the regulation of haematopoietic cell differentiation and maturation.
The discovery of new fluorescent chromophores has further exploited the power of quantitative cellular analysis. These new dyes can be used in combina tion with the standard fluorescein isothiocyanate (FITC) to examine multiple antigens simultaneously. The orange and red emitting dyes-phycoerythrin (PE), tandem conjugates, and peridinin-chlorophyll (PerCP)-can all be excited by a single laser wavelength with their emission separated by bandpass filters (see Chapter 2).
Electron microscopy of filamentous fungi
Authors: O’Connell Richard J , Carzaniga Raffaella 
Published: November 2023

Abstract
Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) have made major contributions to our understanding of fungal cell biology. With the application of modern cryopreparation techniques, such as freezesubstitution, and advances in instrumentation, such as field-emission SEM, electron microscopy continues to generate a wealth of new information on the structure and organization of fungal cells. In addition, cytochemical techniques such as immunogold labelling provide a link between structure and biological function by localizing cell components with exquisite specificity and precision. Despite the obvious advantages of confocal microscopy, especially for live cell imaging, optical methods can never approach the spatial resolution offered by electron microscopy. Now that complete fungal genomes are being sequenced, electron microscopy is set to play an important role in helping to ascribe functions to the vast number of genes identified, for example by revealing the morphology of gene replacement mutants and the localization of gene products.
Human Cytogenetics: malignancy and acquired Abnormalities
Authors: Rooney D E 
Published: November 2023

Abstract
The advent of molecular technologies has lead to a rapid acceleration in the cytogenetic study of malignancy and acquired abnormalities. As well as having a chapter devoted to molecular technologies (FISH, PRINS, and CGH), molecular methodology is emphasized in all chapters, for example the role of CGH in solid tumour cytogenetics. Classical techniques are not forgotten, with a detailed description of the preparation and analysis of chromosomes from bone marrow and leukaemic blood. This is followed by three chapters on the specific methodology for the cytogenetic study of myeloid leukaemia, acute lymphoblastic leukaemia, and lymphomas and lymphoproliferative disorders. Also covered are chromosome instability syndromes, mutagen-induced chromosome damage in lymphocytes and the role of cytogenetics in the assessment of haematological disorders. This book will be invaluable to any scientists using cytogenetics to study malignancy and along with its sister volume Human Cytogenetics: Constitutional Analysis will be an essential purchase for any cytogenetics laboratory. The volumes are available individually or as a set.
Cellular functions of cytosolic E. coli chaperones
Authors: Mock Axel , Bukau Bernd , Deuerling Elke 
Published: November 2023

Abstract
The folding of newly synthesized polypeptide chains into their unique three dimensional structures is of fundamental importance in biology. Protein folding mechanisms were first studied in vitro using purified, chemically denatured polypeptides as substrates. In 1973 Anfinsen demonstrated the correct (re)folding of RNase upon removal of denaturant, suggesting that all the information needed for proper (re)folding was contained in the primary sequence of the protein (1). However, the concept of spontaneous protein folding cannot be extrapolated to living cells.
The roles of the cytosolic chaperonin, CCT, in normal eukaryotic cell growth
Authors: Willison Keith R , Grantham Julie 
Published: November 2023

Abstract
How do polypeptide chains synthesized on soluble polysomes in eukaryotic cytosol proceed to their native states? Is it reasonable to ask such questions of the folding pathways of tens of thousands of different proteins and expect to derive general answers or rules? We suspect that many proteins have sampled enough folding pathways during evolution to have had selected within their sequences chemical properties that allow them to fold up rapidly and concomitantly with chain elongation. The study of proteins which require the cooperation of molecular chaperones to assist their successful folding has provided major insights into understanding some of the problems which proteins face in proceeding to their native states.
Somite and Axial Development in Vertebrates
Authors: Hofmann Clementine 
Published: November 2023

Abstract
The development of the axial skeleton starts with somitogenesis. This is an example of a segmentation process in vertebrates. An initially unsegmented body progressively becomes segmented, leading to the formation of the vertebral column, the most obviously segmented structure in vertebrates. In the mesoderm of all vertebrate embryos, the underlying fundamental patterning process generates periodic blocks of cells, the somites, which form on either side of the neural tube. Somites have been studied in embryos from many vertebrate classes using a variety of experimental methods. However, the majority of studies have been performed in avian and amphibian species, because their embryos are more amenable for experimental manipulations and microsurgery than mammalian embryos. For quite some time, the analysis of somitogenesis and axis formation in mammalian embryos was not the focus of attention, although mutations in mice affecting somites and vertebrae have long been described (reviewed in ref. 1). In the past few years, the zebrafish has emerged as an additional model system for the analysis of somite and axis formation, since the transparency of the embryos allows resulting morphological defects in mutants to be observed and analysed in vivo. The establishment of in vitro culture systems for postimplantation mammalian embryos (2, 3) has also enabled the study of somitogenesis in mammalian embryos. In addition, targeted mutagenesis in the mouse by embryonic stem-cell technology has led to a rapid further understanding of the underlying molecular processes.
Insights into the Molecular basis of Vertebrate Forelimb and Hindlimb Identity
Authors: Kawakami Yasuhiko , Tsukui Tohru , NG Jennifer K , Izpisúa-belmonte Juan Carlos 
Published: November 2023

Abstract
Whilst recently we have gained insights into the molecular and cellular mechanisms that initiate the outgrowth and patterning of the vertebrate limb (reviewed in refs 1–5), very little is known about the mechanisms that determine differences between forelimbs and hindlimbs. In all vertebrates the hindlimb is morphologically distinct from the forelimb, yet both are composed of the same components such as nerves, muscles, blood vessels, and bone. These distinctions are even more striking among species. Compare, for instance, the forelimb and hindlimb of various vertebrates, such as the human arm and leg, the chick wing and leg, and the fish pectoral and pelvic fins. The recent identification of genes specifically expressed in the developing forelimb (Tbx5) and hindlimb (Pitx1 and Tbx4) in vertebrates, including human, mouse, chick, Xenopus laevis, newt, and zebrafish, has begun to aid our understanding of how limb identity is determined. Furthermore, gain- and loss-of-function studies have unveiled how these molecular cues function in the limb field to mediate the development of distinct structures. This chapter will review knowledge about the morphological and molecular basis of forelimb and hindlimb identity in vertebrates, and discuss the roles of Tbx4, Tbx5, and Pitx1 in limb-type specification.
Intersections between HIV and obesity in emerging economies
Authors: Levi Jacob , Fairhead Cassandra , Hill Andrew 
Published: November 2023

Purpose of review
HIV epidemics are increasing in many emerging economy countries, whilst the very process of ‘economic emergence’ is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced.

Recent findings
We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity. We also illustrate the landscape from a selection of ‘emerging economy’ countries with available data from UNAIDS, World Bank and World Obesity Federation to visualize the developing challenges faced. AOM course prices are high in many countries, but could be manufactured and sold profitably for much less. We present lessons from the early HIV/AIDS movements on how to improve access and pricing for AOMs for people with HIV with obesity in emerging economy countries.

Summary
We illustrate the complex intersectional issues that ‘emerging economy countries’ may experience, with a ‘double burden’ of increasing HIV and obesity epidemics, and explore potential mitigation options, focussing on AOM access and pricing.
Surgical Reconstruction for the Triphalangeal Thumb
Authors: Tiourin Ekaterina , Sharpe Frances , Kalina Sharon , Leis Amber R. 
Published: November 2023

Summary:
The triphalangeal thumb poses a complex reconstructive challenge to the congenital hand surgeon due to its rarity and variable anatomy. We discuss the available evidence, reporting clinical characteristics and outcomes of surgical reconstructive procedures of triphalangeal thumb alongside a representative case. The congenital hand surgeon must approach each patient with triphalangeal thumb individually to optimize the use of available tissues to maximize functional and aesthetic outcomes.