bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes
Authors: Pérez-Chacón Gema , Astudillo Alma M. , Ruipérez Violeta , Balboa María A. , Balsinde Jesús 
Published: December 2009

Abstract
Cellular availability of free arachidonic acid (AA) is an important step in the production of pro- and anti-inflammatory eicosanoids. Control of free AA levels in cells is carried out by the action of phospholipase A2s and lysophospholipid acyltransferases, which are responsible for the reactions of deacylation and incorporation of AA from and into the sn-2 position of phospholipids, respectively. In this work, we have examined the pathways for AA incorporation into phospholipids in human monocytes stimulated by zymosan. Our data show that stimulated cells exhibit an enhanced incorporation of AA into phospholipids that is not secondary to an increased availability of lysophospholipid acceptors due to phospholipase A2 activation but rather reflects the receptor-regulated nature of the AA reacylation pathway. In vitro activity measurements indicate that the receptor-sensitive step of the AA reacylation pathway is the acyltransferase using lysophosphatidylcholine (lysoPC) as acceptor, and inhibition of the enzyme lysoPC acyltransferase 3 by specific small interfering RNA results in inhibition of the stimulated incorporation of AA into phospholipids. Collectively, these results define lysoPC acyltransferase 3 as a novel-signal–regulated enzyme that is centrally implicated in limiting free AA levels in activated cells.
Heat Shock Transcription Factor 1 Inhibits Expression of IL-6 through Activating Transcription Factor 3
Authors: Takii Ryosuke , Inouye Sachiye , Fujimoto Mitsuaki , Nakamura Tamami , Shinkawa Toyohide , Prakasam Ramachandran , Tan Ke , Hayashida Naoki , Ichikawa Hitoshi , Hai Tsonwin , Nakai Akira 
Published: December 2009

Abstract
The febrile response is a complex physiological reaction to disease, including a cytokine-mediated increase in body temperature and the activation of inflammatory systems. Fever has beneficial roles in terms of disease prognosis, partly by suppressing the expression of inflammatory cytokines. However, the molecular mechanisms underlining the fever-mediated suppression of inflammatory gene expression have not been clarified. In this study, we showed that heat shock suppresses LPS-induced expression of IL-6, a major pyrogenic cytokine, in mouse embryonic fibroblasts and macrophages. Heat shock transcription factor 1 (HSF1) activated by heat shock induced the expression of activating transcription factor (ATF) 3, a negative regulator of IL-6, and ATF3 was necessary for heat-mediated suppression of IL-6, indicating a fever-mediated feedback loop consisting of HSF1 and ATF3. A comprehensive analysis of inflammatory gene expression revealed that heat pretreatment suppresses LPS-induced expression of most genes (86%), in part (67%) via ATF3. When HSF1-null and ATF3-null mice were injected with LPS, they expressed much higher levels of IL-6 than wild-type mice, resulting in an exaggerated febrile response. These results demonstrate a novel inhibitory pathway for inflammatory cytokines.
T
Lymphocytes: Helpers
Authors: Kawachi Izumi , Kondo Takayuki 
Published: December 2009

Abstract

Helper T lymphocytes are major histocompatibility complex (MHC) class II restricted CD4+ T cells which 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) and T‐follicular helper (T
FH
). Following are several transcription factors especially expressed, or function differently, in each of the clonal progeny to define separable effector T‐helper cell lineages. Helper T cells orchestrate antibody production and cellular immune responses. 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, which is a response aimed mainly at extracellular pathogens. T
H
‐17 cells enhance neutrophil response for extracellular pathogens. Each T
H
subset plays a distinct role in host defence and autoimmunity.

Key concepts

Helper T lymphocytes are MHC class II restricted CD4+ T cells which 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) and T‐follicular helper (T
FH
).

IFNγ, IL‐4 and IL‐17 are the representative cytokines of T
H
1, T
H
2 and T
H
‐17 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 in the defence against intracellular organisms.

T
H
2 cells enhance antibody production from B cells.

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

T
FH
cells regulate the step‐wise development of antigen‐specific B‐cell immunity in B‐cell follicles of lymphoid tissues.
Nucleotide Synthesis
De Novo
Authors: Traut Thomas 
Published: December 2009

Abstract

Nucleosides are composed of a heterocyclic ring (defined as the base) that is attached to a ribose. Addition to a nucleoside of a phosphate, at carbon 5 of the ribose, produces a nucleotide. Nucleotides function as ubiquitous building blocks for the synthesis of all nucleic acids, and also function in enzymatic reactions as cofactors and as a source of energy. These central metabolic roles require their continued biosynthesis from readily available precursors, and this process is defined as

de novo

nucleotide synthesis. The synthesis of purines starts with ribose‐phosphate, to which are attached in a stepwise fashion the individual atoms of the heterocyclic base. Pyrimidine synthesis starts with the stepwise formation of the base, to which is then added the ribose‐phosphate. Bases and nucleosides may also be recycled in salvage pathways.

Key concepts:

Nucleotides are so essential to metabolism that genetic defects generally are lethal, and for humans only a few gene defects are observed, at a low frequency.

Many of the enzymatic reactions in the
de novo
biosynthesis of nucleotides are combined as two or more reactions catalysed by a single multidomain protein. This has made nucleotide biosynthesis more efficient.

For a few of the biosynthetic steps alternate enzymatic strategies have emerged between bacteria and vertebrates, and these present possible targets for drugs as selective antibiotics.
Ploidy Variation in Plants
Authors: Birchler James A 
Published: December 2009

Abstract

Evidence from genome sequences of many plant species indicate that all plants have had a cyclical history of doubling of chromosome numbers, followed by gene deletions back to a near diploid level. Recent cases of increases in genome copy number are generally considered to comprise ploidy variation. Ploidy variation involves changes in the number of whole sets of chromosomes. Aneuploid variation involves changes in the number of individual chromosomes. The two types of chromosomal changes have different consequences for gene expression patterns.

Key concepts:

An increase in whole genome chromosome sets is a recurring process in plant evolution followed by deletion of genes back to a near diploid level.

Recent genome doubling can consist of genomes from slightly diverged species and are referred to as allopolyploids.

Recent genome doubling within a species is referred to as autopolyploids.

Allopolyploids and autopolyploids have different genetic behaviours.

Cell size increases with the number of genomes present, as does gene expression in general.

Aneuploidy is the change in copy number of part of the genome.

Aneuploidy produces greater changes in gene expression than does ploidy variation.
Cardiac Arrhythmias
Authors: Kastor John A , Saba Magdi M 
Published: December 2009

Abstract

Cardiac arrhythmias are disturbances in the rhythm of the heart manifested by irregularity or by abnormally fast (tachycardias or tachyarrhythmias) or abnormally slow (bradycardias or bradyarrhymias) rates. Some produce no symptoms, whereas others can endanger the patient's life. Among the most benign are premature beats that interrupt the normal rhythm of the heart. Tachyarrhythmias include atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia and ventricular fibrillation. Bradycardias include heart (atrioventricular) block and sick sinus syndrome. Antiarrhythmic drugs, cardiac pacing, ablation and implantable defibrillators can control most arrhythmias that need treatment.

Key Concepts:

Cardiac arrhythmias are disturbances in the rhythm of the heart in which the heart beats are irregular, too fast, or too slow.

Cardiac arrhythmias range in severity from asymptomatic to life‐threatening.

Most arrhythmias that require treatment can be controlled by antiarrhythmic drugs, cardiac pacing, ablation and implantable defibrillators.

Some arrhythmias can be treated with ablation in which the physician locates the source of the arrhythmia and, using electrode‐catheters, destroys it.

Premature beats are among the most common cardiac arrhythmias. Specific treatment is seldom required if the patient can be assured that they are benign, which is usually the case.

Atrial fibrillation is the most common sustained cardiac arrhythmia.

Atrial flutter is a rapid rhythm that is best treated with ablation.

In heart block, the electrical signals from the atria cannot reach the ventricles. Symptoms develop when the heart rate slows excessively. Treatment with pacemakers usually relieves the symptoms.

When patients have ventricular tachycardia, the rapid heart rate can produce syncope (fainting). This is a dangerous condition, and electrophysiological treatment is usually required.

Ventricular fibrillation is the arrhythmia that most frequently causes cardiac arrest.
Circular Dichroism: Studies of Proteins
Authors: Kelly Sharon M , Price Nicholas C 
Published: December 2009

Abstract

Circular dichroism (CD) is the differential absorption of the left‐ and right‐circularly polarized components of plane‐polarized electromagnetic radiation. It can provide structural and dynamic information about biological macromolecules, particularly proteins. The CD spectra in the far‐UV (typically 180–240 nm) can give reliable quantitative estimates of the proportions of secondary structural features (helix, sheet, turn, etc.) present in proteins. The spectra in the near‐UV (260–320 nm) can be used to explore the environments of aromatic amino acid side‐chains and hence to give a measure of tertiary structure. Although CD cannot provide the high‐resolution structural data available from X‐ray crystallography or nuclear magnetic resonance, its convenience and applicability under a wide variety of experimental conditions make it the technique of choice in many applications, including exploring protein–ligand interactions, conformational changes and protein folding.

Key concepts:

Circular dichroism (CD) refers to the difference in absorption of the two components (left‐ and right‐circularly polarized) of plane‐polarized radiation.

CD is observed when the absorbing molecule or group exhibits chirality (optical activity).

Protein structures are chiral and so give rise to CD signals.

CD can be used to explore protein structures under a wide range of experimental conditions.

The relatively small CD signals observed from proteins mean that care must be taken to gather reliable experimental data.

CD signals from proteins in the far‐UV and near‐UV can be used to explore their secondary and tertiary structures, respectively.

CD is an ideal technique to monitor conformational changes in proteins which occur on binding to other molecules.

CD can be used to assess the extents of protein unfolding (denaturation) and of refolding of denatured proteins.
Fatty Acid Oxidation Disorders
Authors: Polinati Padmini P , Eskelin Petra , Tyni Tiina 
Published: December 2009

AbstractMitochondrial fatty acid oxidation (FAO) is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A number of inherited disorders affecting this metabolic pathway have been known for almost two decades. Defects of mitochondrial FAO characteristically present with severe metabolic crises associated with low blood glucose (hypoglycaemia) during infancy and childhood and are also a relatively frequent cause of muscle diseases and cardiac muscle disease. The symptoms are typically episodic and often associated with mild viral infections or fasting. Therapeutic interventions are generally effective in preventing metabolic decompensation, which emphasizes the importance of early diagnosis. Diagnostic testing, determining optimal dietary regimens for each disorder and prenatal screening for these disorders may essentially alter an otherwise poor prognosis for many patients with FAO disorders.Key Concepts:Fatty acids can be oxidized by α‐oxidation in peroxisomes, by β‐oxidation in mitochondria and peroxisomes, and ω‐oxidation in the endoplasmic reticulum.Mitochondrial FAO is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress.A single β‐oxidation cycle consists of a series of four repeated enzymatic steps: dehydrogenation (oxidation), hydration, a second dehydrogenation and thiolytic cleavage of the carbon chain.Mitochondrial FAO defects present with severe metabolic crises associated with nonketotic hypoglycaemia, fatty liver, muscle weakness and cardiomyopathy.As a group, mitochondrial FAO defects are among the most common autosomal recessively inherited metabolic disorders.The main objective of therapeutic intervention is to secure sufficient caloric intake during periods of metabolic stress and fasting, and prevent accumulation of β‐oxidation intermediates.Neonatal screening of FAO disorders has been initiated in several countries worldwide, improving the opportunities for early dietary therapies.
Toll‐like Receptors
Authors: Seya Tsukasa , Miyake Kensuke 
Published: December 2009

Abstract

Toll‐like receptors (TLRs) are mainly expressed on antigen‐presenting cells (APCs) and function as adjuvant receptors that modulate cellular immunity. Their pleiotropic functions depend on a variety of signals. Ten members of the TLR family in humans and 10∼20 TLRs in other vertebrates cope with microbial pattern molecules, that is, TLR agonists. In addition, a number of molecules negatively or positively regulate the TLR signal pathways. TLR agonists are capable of activating either of the two main TLR pathways driven by the adaptors, myeloid differentiation primary‐response gene 88 (MyD88) and TRIF (TIR‐containing adaptor‐inducing interferon‐β TIR‐containing adaptor molecule‐1, TICAM‐1), which confer differential maturation modes on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs). Natural killer (NK), CD8 T, CD4 T and B cells are activated through matured dendritic cells. TLRs are therefore involved in not only inducing the acute phase of inflammatory responses but also raising the acquired immune responses including allergy, cancer and infectious immunity.

Key concepts

Innate immune system consists of TLRs, lectin receptors and complement receptors; they recognize foreign and host materials marked or labelled with their ligands.

TLR signal pathways activate transcription factors in affected cells and induce host‐defence agents, including antimicrobial peptides, chemical mediators, cytokines, chemokines and cell‐adhesion molecules.

Dendritic cells play a pivotal role in evoking acquired immunity by liberation of cytokines/chemokines and cell‐to‐cell contact.

There are four adaptors connecting with the TLR TIR domains. These adaptors also possess the TIR domain and directly bind their counterparts. Only myeloid differentiation primary‐response gene 88 (MyD88) and TICAM‐1 (TRIF) are signalling adaptors.

Land‐living vertebrates possess mammalian (M)‐type TLR family, a representative of which is human TLRs. Water‐living vertebrates possess the TLR20 family in addition to the M‐type TLR family.

Plasmacytoid DC is formerly called interferon‐producing cells (IPC).

Tumour necrosis factor receptor–associated factor (TRAF) family proteins act as E3 ubiquitin ligases and closely associated with molecules in the TLR pathways.
Genetics as Explanation: Limits to the Human Genome Project
Authors: Cohen Irun R , Atlan Henri , Efroni Sol 
Published: December 2009

Abstract

Living organisms are composed of cells and all living cells contain a genome, the organism's stock of
deoxyribonucleic acid
(DNA). The role of the genome has been likened to a program that encodes the organism's development and its subsequent response to the environment. This computer metaphor teaches that the organism – the hardware – is controlled by the software – the genome. Thus, the organism and its fate can be explained by genetics, the plans written into the sequence of genomic DNA; the Genome Project was devised to decipher this program. However, it is now clear that the genome does not directly program the organism; the computer program metaphor has misled us. The genome is only one class of vital information that serves the organism. Metaphorically, the genome can be likened to a vocabulary of words that can be deployed to make meaningful sentences, or to a toolbox for accomplishing specific tasks.

Key concepts:

The genome does not function as a master plan or computer program for controlling the organism; the genome is the organism's servant, not its master.

The genome is a reservoir of DNA sequence information and a vehicle for transmitting this information; the meaning of DNA emerges from the cellular processing of this raw information into proteins and other functional molecules.

DNA is only one class of vital information that serves the organism; the organism epigenetically uses, manipulates, regulates and, in the case of the immune system, creates genes.

The effects of a gene vary with the organism's environment; the interactions between genes and environment are not linear and, in most cases, not additive. Therefore, one cannot compute with certainty the relative contributions of genes and environment to an organism's observed features – its phenotype.

Metaphorically, we can think of the genome as akin to a list of words, a vocabulary, which can be used to build and express a meaningful language; like a vocabulary, a genome by itself has no functional meaning.

The genome is thus akin to a toolbox of DNA sequences that provide molecular tools as requested by the internal state of the organism and the state of the environment.

One's genes cannot explain one's being: an organism is the expression of a dynamic and ongoing interaction between the state of its environment and its internal state, which includes its past history and its toolbox of DNA sequences.
Microbial Diversity
Authors: Oren Aharon 
Published: December 2009

Abstract

Prokaryotic and eukaryotic microorganisms dominate life on Earth with respect to the numbers of individuals and biomass. Yet, the number of species of macroorganisms described as well as the estimated numbers of yet to be described species exceeds those of the microorganisms by an order of magnitude. Such numbers give an incomplete picture of the diversity in the microbial world. Only two modes of life are found in higher plants and animals: oxygenic photosynthesis and aerobic respiration. In the microbial world a great variety of processes occur, aerobic as well as anaerobic, phototrophic (oxygenic and anoxygenic), respiratory (with oxygen or other electron acceptors), fermentative and chemoautotrophic (using reduced inorganic compounds as energy sources). Also phylogenetically the microbial world is by far the most diverse. Most branches in the small ribosomal subunit
ribonucleic acid
(RNA)‐based phylogenetic tree contain only microorganisms, whereas higher plants and animals only form short lineages in the eukaryotic branch.

Key concepts

The microbial world encompasses most of the phylogenetic diversity on Earth, as all Bacteria, all Archaea and most lineages of the Eukarya are microorganisms.

The morphological diversity in the microbial world is much smaller than that of the higher plants and animals.

With respect to numbers of individual microorganisms and biomass the microbial world is far more important than the world of macroorganisms, but the numbers of species of microorganisms described to date and the predicted numbers of yet undescribed species are about an order of magnitude lower than those of the macroorganisms.

Based on their modes of energy generation and the variety of organic and inorganic compounds used as energy source and/or nutrients, the microbial world and especially the world of the prokaryotes, has many more possibilities than are realized by macroscopic animals and plants.

Sequencing of microbial DNA isolated from natural environments (environmental genomics, metagenomics) has revealed the existence of a tremendous variety of yet uncultured microorganisms, showing that the true microbial diversity in nature is much higher than currently recognized on the basis of organisms studied in culture.
Phloem Long‐Distance Trafficking of Proteins and
RNAs
Authors: Wolf Shmuel 
Published: December 2009

Abstract

Phloem sap contains a wide range of macromolecules, including
ribonucleic acids
(RNAs) and proteins. Recent advances in genomic and proteomic technologies have enabled the identification of thousands of these macromolecules. However, technical limitations are still the main obstacle to the complete characterization of macromolecule profiles in the sieve tube.

Grafting experiments have established that numerous macromolecules are capable of moving long distances between tissues, providing the foundation for the hypothesis of an interorgan information superhighway in higher plants involving the phloem. This chapter presents the current knowledge on proteins and messenger RNA (mRNA) molecules present in the sieve tube. The challenge now is to characterize the biological role of trafficking macromolecules, such as their involvement in the signal‐transduction pathway(s) elicited by environmental cues and in orchestrating developmental processes at the whole‐plant level.

Key concepts

Phloem sap contains macromolecules such as proteins and RNAs.

Protein profiles in the sieve tube are tissue specific.

Phloem proteins act as long‐distance signalling molecules.

Plant viruses move long distance via the phloem.

Endogenous RNA molecules are capable of trafficking long distance via the phloem.

mRNA molecules may act as long‐distance signalling molecules.