bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutting Edge: Sympathetic Nervous System Increases Proinflammatory Cytokines and Exacerbates Influenza A Virus Pathogenesis
Authors: Grebe Kristie M. , Takeda Kazuyo , Hickman Heather D. , Bailey Adam M. , Embry Alan C. , Bennink Jack R. , Yewdell Jonathan W. 
Published: December 2009

AbstractAlthough the sympathetic nervous system innervates the lung, little is known about its participation in host immunity to pulmonary pathogens. In this study, we show that peripheral sympathectomy reduces mouse morbidity and mortality from influenza A virus-induced pneumonia due to reduced inflammatory influx of monocytes, neutrophils, and NK cells. Mortality was also delayed by treating mice with an α-adrenergic antagonist. Sympathectomy diminished the immediate innate cytokine responses, particularly IL-1, which was profoundly reduced. These findings demonstrate an unexpected role for the sympathetic nervous system in innate antiviral immunity and in exacerbating the pathology of a virus of great significance to human and animal health.
Imaging Nervous System Activity
Authors: Fields R. Douglas , Shneider Neil , Mentis George Z. , O'Donovan Michael J. 
Published: December 2009

AbstractThis unit describes methods for loading ion‐ and voltage‐sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system. Curr. Protoc. Neurosci. 49:2.3.1‐2.3.14. © 2009 by John Wiley & Sons, Inc.
Assessment of Parkinson Disease Manifestations
Authors: Perlmutter Joel S. 
Published: December 2009

AbstractParkinson disease (PD) is a progressive neurologic condition that causes motor and nonmotor manifestations. Treatment provides symptomatic benefit but no current treatment has been proven to slow disease progression. Research studies of PD require a means of rating the severity of disease by measurement of motor manifestations, assessment of ability to perform daily functional activities, and symptomatic response to medication. The most common rating scales are the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr staging, and the Schwab and England rating of activities of daily living. Each of these rating scales are described, including detailed instructions on how to implement these ratings. Although these are the most widely applied rating scales of PD, there are still substantial limitations to these scales that must be considered when using them for research. Finally, some common applications of these scales are described. Curr. Protoc. Neurosci. 49:10.1.1‐10.1.14. © 2009 by John Wiley & Sons, Inc.
EEG Recording and Analysis for Sleep Research
Authors: Campbell Ian G. 
Published: December 2009

AbstractThe electroencephalogram (EEG) is the most common tool used in sleep research. This unit describes the methods for recording and analyzing the EEG. Detailed protocols describe recorder calibration, electrode application, EEG recording, and computer EEG analysis with power spectral analysis. Computer digitization of an analog EEG signal is discussed, along with EEG filtering and the parameters of fast Fourier transform (FFT) power spectral analysis. Sample data are provided for a typical night's analysis of EEG during NREM (non‐REM) and REM sleep. Curr. Protoc. Neurosci. 49:10.2.1‐10.2.19. © 2009 by John Wiley & Sons, Inc.
Neuropsychological Assessment in the Diagnosis of Alzheimer's Disease
Authors: Baldwin Sharelle , Farias Sarah Tomaszewski 
Published: December 2009

AbstractAlzheimer's disease (AD) is the most common form of dementia in older adults. It represents a significant public health concern because of its associated personal, social, and economic burden. As such, AD is the focus of considerable research worldwide. This unit reviews the major cognitive and behavioral impairments associated with AD, and the practical application of current neuropsychological procedures used to assess these deficits.Curr. Protoc. Neurosci. 49:10.3.1‐10.3.8. © 2009 by John Wiley & Sons, Inc.
Bacterial Cell Division
Authors: Lutkenhaus Joe 
Published: December 2009

Abstract

Bacterial cell division or cytokinesis is the process in which a bacterial cell is split into two progeny cells, each with a copy of the chromosome. In most bacteria this process in initiated by the formation of the Z ring, a dynamic structure consisting of polymers of
FtsZ
, a
tublin
family member. The Z ring recruits additional division proteins to form the septal ring, also called the divisome, which leads to the synthesis of the septum separating the progeny cells. Spatial regulation of Z‐ring formation occurs primarily through negative regulators of
FtsZ
assembly that are positioned within the cell. The Z ring forms where the concentration of these negative regulators is at a minimum. A variety of regulators and mechanisms for positioning them have been identified in different bacteria. Among the mechanisms are the binding of a regulator to the segregating chromosome or the divisome itself and a self‐organizing system.

Key concepts:

Division depends on a cytoskeletal element (Z ring) that functions as a scaffold to recruit all the division proteins.

Spatial regulation of Z ring placement involves positioning inhibitors of FtsZ in the cell to prevent FtsZ polymers from coalescing into the ring.

Dynamic self‐organization – the ability of proteins to form dynamic structures and patterns fuelled by nucleotide hydrolysis; the Min system produces an oscillatory pattern and FtsZ filaments have the ability to form rings when attached to a lipid bilayer that has a cylindrical shape.
Ascomycota
Authors: Eriksson Ove E 
Published: December 2009

AbstractThe ascomycetes, the spore sac fungi, are accommodated in the phylum Ascomycota, the largest of the seven phyla of the true fungi with more than 60 000 species. Many are saprobes; others are parasites or live in symbiosis with other organisms. A majority of the lichens are ascomycetes. The ascomycetes are of great economic importance as decomposers of dead material, parasites on crops, producers of antibiotics and other industrial products in food production (bread, beer, wine, etc.).
TransferRNASynthesis and Regulation
Authors: Toh Yukimatsu , Hori Hiroyuki , Tomita Kozo , Ueda Takuya , Watanabe Kimitsuna 
Published: December 2009

AbstractTransferribonucleic acid(tRNA) is primarily synthesized from tRNA gene through transcription byRNA polymeraseand becomes the mature form via several steps: processing, splicing, CCA addition and posttranscriptional modification. Primary transcripts of tRNA genes contain 5′ and 3′ extra sequences, which are removed by a set of responsible nucleases, and introns in some cases, which are spliced out by a specificendonuclease. The resultant two fragments are joined byRNA ligase. The CCA sequences present at 3′‐termini of all mature tRNAs are not encoded in tRNA genes in some species and posttranscriptionally added by a CCA‐adding enzyme. All mature tRNA molecules contain modified nucleotides made by modification enzymes and which are considered to be involved in stabilization of tRNA structure, in decoding properties and in correct processing. The concentration of individual tRNA molecules is controlled to maintain cellular functions.Key concepts:tRNA is synthesized from tRNA gene by RNA polymerase and matured through processing, splicing, CCA addition and posttranscriptional modification.Synthesis of tRNA is regulated by promoter activity and specific factors (ppGpp and/or pppGpp in prokaryotes and Maf1 in eukaryotes) depending on the nutrient condition of the cells.The relative amounts of tRNA are regulated by several factors; the copy number of the tRNA gene, transcriptional activity aforementioned and tRNA degradation by a number of nucleases.Primary transcripts of tRNA genes contain 5′ and 3′ extra sequences, which are removed by a set of responsible nucleases.In some cases tRNA transcripts contain introns, which are spliced out by a specific endonuclease and the resultant two fragments are joined by RNA ligase.CCA‐adding enzyme regulates the amount of active tRNA by repairing CCA sequence at theC‐terminal of tRNA.tRNA possesses a variety of modified nucleotides which are introduced by modification enzymes during or after the processing, splicing and transport steps.Several modifications in tRNA play important roles in the translation process, such as enhancement, expansion, restriction and/or alteration of codon–anticodon interactions, stabilization of tRNA structure, recognition by aminoacyl‐tRNA synthetase, etc.
Methanogenesis Biochemistry
Authors: Lessner Daniel J 
Published: December 2009

Abstract

Methanogenesis is the biological production of methane mediated by anaerobic microorganisms from the Archaea domain commonly called methanogens. The production of methane is the energy‐yielding metabolism of methanogens and is unique to these organisms. Methane is produced by three major pathways: (1) reduction of carbon dioxide, (2) fermentation of acetate and (3) dismutation of methanol or methylamines. All three pathways have in common the demethylation of methyl–
coenzyme M
to methane and the reduction of the heterodisulfide of
coenzyme M
and
coenzyme B
catalysed by
methyl–coenzyme M
and
heterodisulfide reductases
. Investigations of the biochemistry of the pathways have revealed novel enzymes with metal and cofactor requirements that have introduced new principles of biochemistry.

Key Concepts

Methanogenesis is the final step in the biological decomposition of biomass in the absence of oxygen.

Approximately 70% of biologically produced methane originates from conversion of the methyl group of acetate to methane.

The pathway of methanogenesis involves enzymes with novel cofactor and metal requirements.

Nickel is an essential metal that is found in the active site of carbon monoxide dehydrogenase, hydrogenase, and methyl–coenzyme M reductase, an enzyme which is common to all methanogenic pathways.

Methyltransferases involved in the metabolism of methylamines by
Methanosarcina
species contain pyyrolysine, the 22nd amino acid.

Comparative genomics combined with biochemical analyses have revealed variations in the enzymes involved in the energy‐conservation steps in methanogens.

Energy conservation in methanogens is linked to the generation of a chemical gradient that drives ATP synthesis by an ATP synthase.
Immunoglobulin Gene Rearrangements
Authors: Lieber Michael 
Published: December 2009

Abstract

V(D)J and class switch recombination are two
deoxyribonucleic acid
(DNA) recombination processes that occur at immunoglobulin genes during the generation of B cells and the attendant rearrangement of immunoglobulin heavy and light chain loci. V(D)J occurs during early B‐ and T‐cell development whereas class switch recombination occurs exclusively in mature B cells. V(D)J recombination achieves the assembly of new exons that encode the portion of the antigen receptor that binds antigen. Class switch recombination changes the constant portion of the heavy chain of the antibody from IgM to IgG, IgA or IgE. V(D)J recombination occurs in the bone marrow for pre‐B cells and in the thymus for pre‐T cells. Class switch recombination occurs in the germinal centres in the spleen, lymph nodes and Peyer's patches.

Key Concepts:

V(D)J recombination occurs only in vertebrates, because these are the only organisms that have lymphocytes and that generate B and T cells with antigen receptors.

V(D)J recombination is done by the RAG1 and RAG2 proteins, which bind at recombination signal sequences (RSS) that consist of heptamer and nonamer recognition sequences.

The RAG complex (consisting of RAG1 and RAG2, along with HMGB1) is only expressed in pre‐B cells and pre‐T cells.

Class switch recombination requires activation‐induced deaminase (AID).

AID acts only on single‐stranded DNA.

For class switch regions, single‐stranded DNA is generated by the formation of R‐loops at the switch regions.

Switch regions consist of unit repeats (25–80 bp in length) that are 40–50% G on the nontemplate strand, making them prone to form R‐loops.

Occasionally, the RAG complex or AID act at off‐target sites, thereby triggering double‐strand breaks that can cause the chromosomal translocations that initiate many types of lymphomas or lymphoid leukaemias.
Protein Kinases: Signatures in Cancer
Authors: Sowadski Janusz M , Suto Robert K 
Published: December 2009

Abstract

Since the discovery of the first
protein kinase
crystal structure, structures of over 50
protein kinases
have been solved. This crystallographic tour‐de‐force has catalysed structure‐based design of specific inhibitors, resulting in over 100 000 patent protected molecules. One‐third of the pharmaceutical industry R&D worldwide is directed towards kinase inhibition. Concerted efforts resulted in Food and Drug Administration approval for several drugs including the most successful oncology drug – imatinib (Gleevec) developed by Novartis. The challenge now is to overcome drug resistance and increase drug efficacy through genetic patient stratification in clinical trials and clinical practice. Clinical data of
deoxyribonucleic acid
(DNA) sequences that contain key genes serve as the basis for establishing signatures for responding patients and allow the ‘tailoring’ of a particular drug to specific patient populations. Such a signature‐based approach can enhance the value of already approved drugs and may be used to treat patients with different cancer subtypes.

Key concepts:

All kinase inhibitors that are FDA approved as first in line oncology drugs compete with ATP binding to the kinase catalytic core.

Clinical responses of CML cancer patients to imatinib depend on the specific genetic signatures of the patients.

Resistance of CML patients to imatinib can be overcome by structure‐based redesigning of the inhibitor molecule.

Imatinib can treat cancer patients with very different cancer subtypes, such as CML and GIST.

CML and GIST patients responding to imatinib have common activating kinase mutations.

Only 10% of NSCLC patients respond to gefitinib or erlotinib; these responding patients have specific genetic signatures.

Activating mutants of responding NSCLC patients have a lower affinity to ATP.

There is a common site in the catalytic core of kinases where mutations can lead to higher affinity to ATP and this site can also be associated with patients who develop resistance to imatinib, gefinitib and erlotinib.
Polymerase Chain Reaction (
PCR
)
Authors: Metzker Michael L , Caskey C Thomas 
Published: December 2009

Abstract

Polymerase chain reaction (PCR) is a rapid,

in vitro

deoxyribonucleic acid
(DNA) synthesis process, which can amplify up to a billion copies of a given nucleic acid target. It has been extensively applied for the identification, detection and diagnosis of genetic and infectious disease. In the article, we provide a general overview of the PCR process, describe methods to identify and minimize exogenous contamination, and highlight limitations of product size and polymerase‐dependent errors. We present many of the applications for which PCR is used, particularly in creating recombinant DNA constructs, in detecting genetic variation, in preparing templates for DNA sequence analysis and in quantitating gene transcripts or viral copies. Whole genome amplification and the ligation chain reaction are also presented, which we believe this article provides the reader with a comprehensive viewpoint of the variety of amplification‐based methods used in molecular biology today.

Key Concepts

Polymerase chain reaction is an
in vitro
amplification method widely used in molecular biology.

PCR contamination can occur from a single molecule of foreign or exogenous DNA, which, if gone unchecked, can confound the interpretation of results.

PCR cloning of full‐length genes can be problematic because mutations can result in amino acid substitutions in wild‐type sequences.

PCR can reliably amplify target sizes up to 3–4 kb from a variety of source materials.

Recombinant PCR products can be created by mismatching sequences between the primer and the template DNA or by adding 5′ exogenous sequences to the primers.

PCR can detect human genetic variation associated with hereditary disease and cancer.

Degenerate PCR is a powerful tool for identifying novel gene family members that are important in drug development.

Quantitative PCR has been widely used for studying gene expression and estimating viral copy number.

Emulsion PCR is used to prepare templates in a cell‐free system for next‐generation sequencing platforms.

Whole genome amplification uses the highly processive φ29 DNA polymerase to amplify nanogram quantities of precious samples into microgram amounts.
Systemic Signalling in Plant Defence
Authors: Helliwell Emily E , Yang Yinong 
Published: December 2009

Abstract

Systemic signalling involves a complex network of signal transduction and amplification that leads to the activation of defence genes and establishment of systemic resistance throughout the entire plant. On microbial invasion, pathogen‐associated molecular patterns and effectors are frequently detected and recognized by plant receptors. Localized perception at the infection site rapidly triggers a cascade of early signalling events such as ion fluxes, protein phosphorylation and production of reactive oxygen species. Subsequently, secondary signal molecules are synthesized and involved in amplification of defence signalling and the establishment of systemic acquired resistance. In addition, crosstalks often occur among various signalling pathways, which further modulate host defence in response to different types of pathogen attack.

Key concepts:

Local resistance to pathogen infection generally results from PAMP (pattern‐associated molecular pattern)‐triggered immunity, otherwise known as basal defence, and microbial effector‐triggered immunity.

Microbial infection of local tissues often leads to systemic acquired resistance in distal tissues which provides long‐lasting broad‐spectrum resistance to a variety of pathogens.

Mobile signals for systemic acquired resistance are translocated via vasculature and may include small peptides such as AtPep1, methyl salicylate, jasmonate, azelaic acid and other lipid‐derived molecules.

Both local and systemic resistance involve a complex network of signal transduction which includes extensive crosstalks among reactive oxygen species (e.g. hydrogen peroxide and nitric oxide), salicylic acid, jasmonic acid, ethylene, abscisic acid, auxin and MAP kinase signalling pathways.
Cholesterol Metabolism and Vascular Disease
Authors: Olufadi R , Wild SH , Byrne CD 
Published: December 2009

AbstractCholesterol is packaged into lipoprotein particles in the liver and intestine and transported to peripheral tissues for normal cellular function. Reverse cholesterol transport is the mechanism by which excess cholesterol is transported back to the liver and is facilitated by high‐density lipoproteins (HDLs). Increased plasma concentrations of cholesterol within the low‐density lipoprotein (LDL) contribute to atherosclerotic vascular disease that commonly affects the coronary, cerebral and peripheral vascular circulation. Incontrovertible evidence now supports the use of the ‘statin’ class of drugs to decrease vascular disease. Statins inhibit hepatic cholesterol synthesis, increase hepatic low‐density lipoprotein cholestrol (LDLc) receptor expression and consequently decrease plasma LDLc, to reduce risk of myocardial infarction in people at widely varying risk of heart disease. At present, there is limited evidence to support the use of drugs that modify high‐density lipoprotein cholesterol (HDLc) to reduce risk of heart disease.Key conceptsEndogenous and exogenous lipid pathways.Hypercholesterolaemias.Low‐density lipoprotein cholesterol (LDLc) and heart disease.High‐density lipoprotein (HDL) metabolism.Modification of high‐density lipoprotein cholesterol (HDLc) and heart disease.Pathophysiology of vascular disease in relation to lipid metabolism.
Calorimetry
Authors: Lewis Edwin A 
Published: December 2009

Abstract

In biology, particularly in studies relating the structure of biopolymers to their functions, two of the most important questions are: (1) how tightly does a small molecule bind to a specific interaction site and (2) if the small molecule is a substrate and is converted to a product, how fast does the reaction take place? Since almost any chemical reaction or physical change is accompanied by a change in heat or enthalpy, an isothermal titration calorimeter (ITC) is an ideal instrument to measure either how much of a reaction has taken place or the rate at which a reaction is occurring. In contrast to optical methods, calorimetric measurements can be done with reactants that are spectroscopically silent (a chromophore or fluorophore tag is not required), can be done on opaque, turbid or heterogeneous solutions( e.g. cell suspensions) and can be done over a range of biologically relevant conditions (temperature, salt, pH, etc).

Key Concepts

Almost all chemical reactions are accompanied by a change in heat or enthalpy.

Calorimetry can determine the complete set of thermodynamic parameters that characterize binding reactions, e.g. K, Δ
G
°, Δ
H
°, Δ
S
° and Δ
C
p
.

Binding reactions are typically pH, salt and temperature dependent.
Nature/Nurture – A Philosophical Analysis
Authors: Ariew André 
Published: December 2009

AbstractThe debate about whether some attribute is ‘by nature’ or ‘by nurture’ has a long history and it covers numerous topics. For instance, Socrates proposed that our ideas of complex concepts come from memories that are innate within us. Even today thinkers believe that some of our ideas are part of our nature rather than our nurture. This theory has social and policy implications. If intellectual quotient (IQ) is a fixed part of nature, is it worthwhile to contribute tax dollars to improve one's nurturing environment? Or, more generally, some think that understanding human nature might affect how we ought to live. Influenced by Darwin and developments in genetics, the nature/nurture debate has reduced to a debate about whether our attributes are ‘genetic’ or ‘environmental’. Yet, the implications of the genetic theories of human nature are not obvious since genes alone do not produce any attributes.Key concepts:‘Nativists’ employ ‘poverty of stimulus’ arguments to demonstrate that an idea or cognitive ability could not have been learned.‘Empiricists’ believe that our beliefs about the world come from our perceptual connection to the world and not from our natures.IQ is likely to be influenced by nurturing environments.Likely, there is no such thing as the singular good life; rather there are numerous valid conceptions of the good life.The gene/environment dichotomy is false but that does not mean we cannot distinguish between robust and plastic developmental events.