bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukins
Authors: Meager Anthony , Wadhwa Meenu 
Published: September 2013

AbstractThe interleukins are a major class of biologically active protein mediators, known as cytokines, that following release from activated cells bind to specific cell surface receptors to induce growth and differentiating functions in target cells. Extensive studies into their genes, structures, receptors, signal transduction pathways and activities in experimental cell cultures have provided considerable knowledge leading to their molecular and biological characterisation. Fundamental findings are that they are mostly pleiotropic mediators, that is, act on more than one cell type or at different stages of cellular development, and stimulate multiple activities, especially where acting in combinations of two or more interleukins. Their production as essentially pure recombinant proteins has enabled studies in experimental model systems to determine whether their activities could be of clinical benefit, or harmful. Subsequently, several interleukins and their antagonists have been evaluated for clinical efficacy and safety in clinical studies, and have yielded promising, though not fully effective, therapeutic treatments for patients with cancer and autoinflammatory diseases. In this article, the molecular characteristics of interleukins, their cognate receptors and intracellular signalling pathways, their biological activities and their potential clinical uses are briefly described.Key Concepts:Interleukins are a broad class of biologically active proteins with hormone‐like actions that regulate the development, differentiation and functions of cells of the immune and haematopoietic systems.The activities of interleukins are mediated via cell surface receptors.Binding of interleukins to receptors triggers gene induction via the activation of intracellular signal transduction pathways.Interleukins exhibit complex biological interactions, both among themselves and with other molecular mediators,in vivo.The proinflammatory and immune‐stimulatory activities of interleukins are essential for host defence against pathogens.Interleukins can be ‘two‐edged swords’, being largely beneficial to the host at low concentrations but deleterious and toxic at high concentrations.The biological properties of interleukins have suggested their potential for development as therapeutic drugs (biopharmaceuticals) against infections and chronic diseases, such as cancer, but so far only a few have proved clinically useful.Antibody and receptor antagonists of interleukins are showing promise for the treatment of autoinflammatory and autoimmune diseases, such as irritable bowel disorders and RA.
Kidney Development
Authors: Davies Jamie 
Published: September 2013

AbstractMammals produce three pairs of kidneys: the pronephros and mesonephros are discarded during fetal life whereas the metanephros remains as the permanent excretory organ. It forms when two progenitor tissues – ureteric bud and metanephrogenic mesenchyme – meet and exchange signals. These signals cause the bud to branch repeatedly to form the urinary collecting duct system and cause the mesenchyme to create a stem cell population, and elements of that population to differentiate into excretory nephrons and supporting cells. Further exchanges of signals control endothelial invasion to make the blood system, and the process of innervation. They act by linking to cellular morphogenetic effectors. Many important questions about renal development remain unanswered; some are listed in this article.Key Concepts:Development of the permanent mammalian kidney (metanephros) occurs almost autonomously, so that even a kidney rudiment in culture, isolated from the rest of the embryo, will develop most of the anatomical features of a normal fetal kidney (but not vascularisation or innervation). The ability to build a kidney is therefore largely a property of the 2–3 cell types present in the rudiment.The precise anatomy of the kidney, like many other organs, is flexible and responsive to environmental influences (mechanical, chemical and hormonal): its general layout may be specified genetically but its microarchitecture is not.Elements of the kidney develop in a specific order: in any given part of the kidney, the collecting duct system, which defines the renal architecture, begins to develop first. Nephrons develop next, with the blood and nervous systems following so that they connect to the nephrons already present. Development continues centrifugally, so that the outer part of the kidney is (until development ceases near birth) still undergoing ‘early’ events, for example, nephron induction, while the central core is much more mature.Kidney development depends on, and is coordinated by, the exchange of signals between cells that regulate motility, proliferation, survival and differentiation.Genetic defects in signalling pathways or in the effector systems that they should trigger result in a significant fraction of common human congenital abnormalities. Mechanical defects in the rest of the embryo can also cause congenital renal defects.The kidney does contain stem cells even after the development has completed, but its capacity for regeneration is limited.There is a major, freely accessible database for urogenital development –http://www.gudmap.org
T
Lymphocytes: Helpers
Authors: Kawachi Izumi , Kondo Takayuki 
Published: September 2013

Abstract

Helper T lymphocytes (T
H
) are major histocompatibility complex (MHC) class II restricted CD4
+
T cells that can be divided into several subsets depending on their cytokine releasing patterns: T‐helper 1 (T
H
1), T
H
2, T
H
17, T‐follicular helper (T
FH
), forkhead box P3
+
regulatory T (Treg) cells and the recently described T
H
9 and T
H
22 cells and others. T
H
1 cells activate infected macrophages for the destruction of intracellular pathogens. T
H
2 and T
FH
cells provide help to B cells for antibody production. T
H
17 cells enhance neutrophil response for extracellular pathogens. Treg cells actively suppress immune reactions and help prevent the development of autoimmunity during immune response. It was initially thought that each T
H
subset retained a stable phenotype with a distinct lineage and played a distinct role in host defense and autoimmunity. Considerable overlap and flexibility of cytokine production by CD4
+
T cells is challenging earlier concepts.

Key Concepts:

Helper T lymphocytes (T
H
) are MHC class II restricted CD4
+
T cells that can be divided into several subsets of cytokine releasing patterns: T‐helper 1 (T
H
1), T‐helper 2 (T
H
2), T‐helper 17 (T
H
17), regulatory T (Treg), T‐follicular helper (T
FH
) and others.

T
H
cell subsets express a distinct set of genes that encode hallmark cytokines and unique transcription factors.

IFN‐γ, IL‐4, IL‐17, IL‐10/TGF‐β and IL‐21 are the representative cytokines of T
H
1, T
H
2, T
H
17, Treg and T
FH
cells, respectively, and are often used as subtype markers.

T
H
1 cells play an important role in cellular immune functions such as delayed‐type hypersensitivity or defense against intracellular organisms.

T
H
2 cells enhance antibody production by B cells.

T
H
17 cells are potent inducers of tissue inflammation in autoimmune diseases and confer protection against extracellular bacterial and fungal pathogens.

Treg cells consist of a heterogeneous class of cells that suppress T‐cell activity and help prevent the development of autoimmunity during immune response.

T
FH
cells regulate the step‐wise development of antigen‐specific B cell immunity in B cell follicles of lymphoid tissues.
Molecular Evolution: Patterns and Rates
Authors: Bromham Lindell 
Published: September 2013

Abstract

The rates and patterns of evolution of
deoxyribonucleic acid (DNA)
sequences vary among species, across the genome and between sites in a gene. These patterns can be considered in the light of the rate and type of mutations, and the forces that determine which of these mutations become substituted in the population. Mutations can rise in frequency if the individuals carrying those mutations leave proportionally more offspring. If a mutation increases in frequency until it replaces all other alternatives in the population, it becomes a substitution, carried by all members of that population. Substitution is driven by selection and chance, and the relative power of each of these processes is affected by population dynamics. The complexity of patterns and rates of DNA sequence evolution create a rich record in the genome of evolutionary mechanisms and history.

Key Concepts:

Mutations are heritable changes to the DNA sequence, created by damage to DNA or by errors made when DNA is copied.

Mutations occur in individual genomes, and are inherited in copies made from those genomes.

A beneficial mutation that increases the chances of its carrier successfully reproducing will tend to increase in frequency over generations (positive selection).

A deleterious mutation that decreases the chances of its carrier successfully reproducing will tend to decrease in frequency over generations (negative selection).

A neutral mutation that has no effect on fitness can increase in frequency through random sampling, and may become fixed in the population by chance (drift).

In small populations, drift can overwhelm selection for mutations with a small impact on fitness, so the rate of fixation of slightly deleterious mutations should be greatest in small populations.

The interaction between selection and drift creates complex patterns of molecular evolution across the genome, over time and between species.
Macrophage Function Disorders
Authors: Lee Keith M , Yin Charles , Verschoor Chris P , Bowdish Dawn ME 
Published: September 2013

AbstractMacrophages are sentinel cells of the innate immune response. Macrophages recognise pathogen‐associated molecular patterns (e.g. microbial products) and endogenous ligands (e.g. apoptotic cells) through a broad and adaptable range of pattern‐recognition receptors. The consequence of this recognition is generally effective clearance via phagocytosis; however, when this is not effective, macrophages may become inappropriately activated and initiate an inappropriate inflammatory response. Because macrophages are extremely variable in phenotype and function and share a common ancestry with monocytes and dendritic cells, there are very few genes that are expressed exclusively in macrophages. Consequently, macrophage‐specific immunodeficiencies are rare. There are, however, a number of genetic immunodeficiencies that affect macrophage function. In addition, as macrophages are exquisitely attuned to their microenvironment, their function appears to be adversely affected by and contributes to chronic inflammatory conditions such as cancer, atherosclerosis and obesity. Thus, genetic deficiencies, in addition to microenvironmental dysregulation, can contribute to macrophage function disorders.Key Concepts:Macrophages functions include sensing of modified host proteins, microbes and microbial components. Macrophages respond to these ligands primarily through phagocytic and inflammatory receptors.Macrophage function is exquisitely attuned to the microenvironment and when chronic inflammatory conditions alter the microenvironment, macrophage function can become impaired.Primary immunodeficiencies have been identified that impair macrophage phagocytosis and inflammatory responses and leave the patient susceptible to infectious disease and other chronic conditions.Macrophages are able to sense a wide and diverse variety of endogenous and exogenous ligands, including modified host proteins, microbes, and microbial components.Chronic inflammatory conditions such as cancer and atherosclerosis alter the microenvironment, which can impair the ability of macrophages to maintain homeostasis.
Protein Denaturation and the Denatured State
Authors: Hammarström Per , Jonsson Bengt‐Harald 
Published: September 2013

Abstract
Protein denaturation experiments are routinely used to determine protein stability and to elucidate structural and dynamic effects of mutations, cofactors and ligands. Denatured states of proteins have gained wide interest in recent years owing to their fundamental importance in a wide variety of phenomena such as deciphering the protein folding problem and the molecular understanding of many diseases. Because the integrity of the folded protein structure is strongly affected by environmental factors denaturation is often studied by monitoring the effects of increasing temperature, changing pH or addition of chaotropic agents such as urea and guanidinium chloride. The structural and dynamical effects of denaturation are most efficiently characterised by using a combination of spectroscopic methods most notably circular dichroism, fluorescence and nuclear magnetic resonance. Amide hydrogen–deuterium exchange experiments can efficiently characterise partly unfolded protein structures.

Key Concepts:

There are many spectroscopic methods to study protein denaturation and denatured states.

Transitions between folded and denatured conformations of proteins are often highly cooperative.

Denatured states of proteins are ensembles of rapidly converting conformations on the nanosecond timescale.

Denatured states of proteins possess residual structures which often reside within hydrophobic cores.

Denatured states of proteins can be informative of the protein folding pathway.
Architecture of Membrane Proteins
Authors: Shlykov Maksim A , Yee Daniel C , Saier Milton H 
Published: September 2013

AbstractBiological membranes are exquisite multifunctional structures that border all living cells and intracellular organelles in virtually all types of organisms from bacteria to man. In addition to the fundamental phospholipid unit, present in most bacteria and eukaryotes, and the dominant ether lipids present in many archaea, other lipids, proteins, carbohydrates and sterols contribute to the lipid bilayer. Most important, from a functional perspective, are the specialised membrane proteins of diverse functions that are embedded in or associated with membranes. Membrane architectural features and the methods used to gain relevant information are presented. Integral, peripheral and lipid‐anchored membrane proteins as well as the inhomogeneity of membranes are considered from structural, functional and evolutionary standpoints. Transport proteins that provide avenues of communication and material exchange, and toxins that target membranes and kill cells by creating transmembrane pores, are discussed in some detail, especially from mechanistic points of view.Key Concepts:Architecture of membranes and membrane proteins.Functions of transmembrane proteins.Membrane microcompartmentalisation.Protein pore‐forming toxins.Lipid rafts and caveolae.
Phylogenetic Likelihood
Authors: de Oliveira Martins Leonardo , Mallo Diego , Posada David 
Published: September 2013

Abstract

The input data for any phylogenetic analysis is a set of characters belonging to different individuals or loci, and assumed to have a common ancestor. Given a set of aligned
deoxyribonucleic acid (DNA)
or protein sequences, the likelihood of a phylogenetic tree depicting their ancestry relationships will be proportional to the probability of the alignment having been generated along this tree. The likelihood can be used not only as an objective criterion to find the optimal phylogenetic tree, but also to compare trees and evolutionary models, always in a probabilistic framework. The likelihood is the central ingredient of any statistical phylogenetic analysis, as it makes the connection between the data (the alignment) and the model, including the tree, branch lengths and other evolutionary assumptions.

Key Concepts:

The phylogenetic likelihood is the probability of the DNA sequence alignment X given a model of nucleotide substitution with parameters θ and phylogenetic tree τ (topology plus branch lengths).

The phylogenetic likelihood can be similarly calculated for amino acid or coding sequences, and they are all based on the instantaneous probability of a change of state.

The phylogenetic likelihood is the basis for any probabilistic phylogenetic inference, for both classical and Bayesian analyses.

There are many substitution models available, and the likelihood allows us to compare them and to find the best model, as well as the best phylogenetic tree.

In maximum likelihood phylogenetic estimation, the objective is to find the set of parameter values, particularly tree topology and branch lengths, that maximize the likelihood function.

In a Bayesian setting, the posterior probability of a particular set of phylogenetic parameter values (e.g. topology and branch lengths) is proportional to their likelihood multiplied by the prior probability of these values. The objective is then to describe these values with their associated posterior probabilities.
Genomic
DNA
: Purification
Authors: Tümmler Burkhard , Stanke Frauke 
Published: September 2013

Abstract

Genomic
deoxyribonucleic acid (DNA)
can be prepared from any source by three steps: cell lysis, deproteinisation, and recovery of DNA. The basic protocol needs to be adapted to the demands of the application, the number of samples to be processed, the requested yield, purity and molecular weight of the DNA, and the amount and history of the source. Traditional protocols based on the lysis with sodium dodecyl sulfate/proteinase K, extraction with phenol/chloroform/isoamyl alcohol, purification with ethanol and storage in Tris/ethylenediamine tetraacetic acid buffer are recommended for the purification of long‐term stable high‐molecular weight genomic DNA from freshly obtained specimens. Intact chromosomal DNA is recovered from agarose‐embedded cells. Automated extraction methods are preferred for forensic applications and high‐throughput processing for biobanking. The technically challenging recovery of ancient DNA needs to be optimised on a case‐to‐case basis, because ancient DNA is damaged and chemically modified and contains large amounts of polymerase chain reaction inhibitors.

Key Concepts:

The analysis of complex genomes requires the preparation of pure genomic deoxyribonucleic acid (DNA) of high molecular weight.

Genomic DNA can be prepared from any source by three steps: cell lysis, deproteinisation and recovery of DNA.

Intact chromosomal megabase‐sized DNA is purified in solid agarose to protect the DNA during preparation.

DNA extraction for biobanking relies on automated systems and robotics.

Automated systems have been increasingly utilised for DNA extraction by forensic laboratories to handle the growing numbers of forensic casework samples while minimising the risk of human errors and assuring high reproducibility.

The recovery of ancient DNA from palaeontological specimens is a demanding task, because ancient DNA is damaged and chemically modified and contains large amounts of PCR inhibitors that interfere with DNA amplification that are copurified with the DNA.
Stomatal Patterning
Authors: Bringmann Martin , Bergmann Dominique C 
Published: September 2013

Abstract

Stomatal development is a model for understanding the integration of multiple inputs into a simple cell fate choice. Intense research during the past decade has revealed mechanisms that govern stomatal development including inter‐ and intracellular signalling, transcriptional regulation, cell polarisation and asymmetric cell divisions. Recent discoveries in
Arabidopsis
include conserved families of transcription factors that drive differentiation and morphogenesis in the stomatal lineage. Specific proteins and pathways that mediate the transduction of signals, and thereby contribute to fate decisions such as secreted protein ligands, receptor kinases, mitogen activated protein kinase kinases and light and hormones have also recently been described. Studies in
Arabidopsis
and maize revealed novel proteins polarised within dividing stomatal lineage precursors. Together, these discoveries set the foundation to untangle mechanisms that lead to pattern and cell fate acquisition in plant systems.

Key Concepts:

Stomata are cellular pores that regulate gas exchange in plant leaves.

Stomatal density and distribution is modulated by the environment and responds to changes in light, CO
2
and humidity.

Stomatal development provides a framework for the understanding of cell fate, cell–cell signalling and cell polarity in plants.

Progression through the stages of stomatal development in
Arabidopsis
requires a balance of fate promoting transcription factors, and fate and division repressing cell–cell signalling.

Based on genetic studies, plants and animals display considerable conservation in the molecules and mechanisms used for developmental fates, but plant‐specific modules are used to generate physically asymmetric cell divisions that characterise early stomatal development.
Evolution of the Human Immune System
Authors: Danilova Nadia 
Published: September 2013

Abstract

Human immune system is an orchestra of various defence mechanisms functioning at different levels, from individual cells to the whole body. Specialised immune mechanisms can be subdivided into innate and adaptive immune systems. Innate immune mechanisms use receptors recognising conserved molecular patterns of pathogens. Adaptive immune system depends on the production of vast repertoires of immune receptors and selective expansion of pathogen‐specific ones. Some basic cellular functions such as ubiquitination and autophagy as well as stress response pathways also contribute to the immune defence. Various immune defence systems work autonomously but in communication with each other. All responses are coordinated at the body level by hormones and other mediators. Layered and redundant structure of the human immune system offers great efficiency in the detection and elimination of pathogens. All immune mechanisms evolve interactively in concordance with human environment and history.

Key Concepts:

Human immune system is a multilayered structure that includes various mechanisms.

Basic cellular mechanisms may contribute to immune defence.

Specialised immune mechanisms are subdivided into innate and adaptive based on the receptors used for antigen recognition.

Immune mechanisms comprise those based on humoral factors and those based on cells.

Most immune defence mechanisms work semiautonomously in interaction with other systems.

Immune mechanisms can be controlled at the body level by hormones and other mediators.

Immune receptors evolve by gene duplication, balancing selection, changes in coding and regulatory sequences, and other mechanisms.

Human immune system continues to evolve.

Individual immune mechanisms evolve in interaction with other mechanisms and basic cellular machinery.