bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunology of Invertebrates: Cellular
Authors: Smith Valerie J 
Published: April 2010

Abstract

Circulating (free) cells are the main mediators of immunity in invertebrates, carrying out the phagocytic, encapsulating and microbicidal responses that enable these animals to protect themselves against infection without a specific adaptive immune system. The cells are specialised for these functions, with division of labour between types. In general, immune cell diversity tends to increase with body complexity and life histories but common to the majority of species, however, are phagocytic and granular cell types that synthesise and store bioactive proteins. The release of these compounds occurs by exocytosis following interaction of pattern recognition receptors and nonself motifs carried on the surface of pathogens or parasites. Cell death of one form or another appears to be inherent in immune reactivity of many invertebrates with new cells produced, at least in coelomates, by mesodermal haemopoietic tissues.

Key concepts

Immunity in invertebrates is confined to nonspecific inflammatory responses, mediated to a large extent by the circulating blood cells (haemocytes or coelomocytes) or their products.

All coelomate invertebrates contain populations of freely circulating cells dedicated to host defence, some well developed for specialist purposes.

There are no true vertebrate‐type lymphocytes and no long‐term, highly specific immune memory in invertebrates.

The main invertebrate cellular immune responses include phagocytosis, encapsulation, cytotoxicity and the synthesis and release of microbicidal agents.

These cellular reactions often involve the death of immune cells or their removal from the circulation, requiring new cells to be synthesised in the haemopoietic tissue and released into the blood.

Genomic and proteomic studies have enabled many of the proteins responsible for cellular defence in invertebrates to be identified, especially in arthropods.

Although many of the responses and pathways are ancient and highly conserved, there is great diversity in the effector molecules across the invertebrates as a whole.
Nuclear‐encoded Protein Import into Chloroplasts: Methods
Authors: Soll Jürgen , Bölter Bettina 
Published: April 2010

Abstract

Chloroplasts carry out essential processes, for example photosynthesis. They are derived from an endosymbiotic event, in which an ancient cyanobacterium was engulfed by an eukaryotic ancestor. During evolution, most of the genes have been transferred to the nucleus. Consequently, >98% of all plastid proteins are translated on cytosolic ribosomes and posttranslationally targeted to and imported into the organelle. Targeting is assisted by cytosolic proteins, which keep them in an import‐competent state. At the chloroplast, many proteins have to conquer the barrier of the chloroplast envelopes. This process is mediated by two complexes in the outer (Toc) and inner (Tic) envelope. Most proteins destined for inner compartments contain a cleavable
N
‐terminal transit peptide, whereas most outer envelope components insert into the membrane without such a targeting peptide. Investigation of the import of nuclear‐encoded proteins into chloroplasts is an essential field of plant science. To throw light on this very basic process many different methods have been established.

Key Concepts:

Studying the
in vitro
import behaviour of chloroplastic preproteins gives essential insight into this fundamental process.

Analysis of mutants in model organisms provides information about the
in vivo
function of proteins proposed to be involved into translocation.
Sedimentation
Authors: Maxon Laue Thomas 
Published: April 2010

Abstract

Sedimentation is a classic method of biochemistry that provides first‐principle hydrodynamic and thermodynamic information about the purity, size, shape, molar mass, association energy, association stoichiometry and thermodynamic nonideality of molecules in solution. The fundamental measurement in sedimentation is the concentration as a function of radial position. Any of the three optical systems provides the necessary concentration profiles, making sedimentation a versatile tool for analysing biological solutions. There are two distinct sedimentation methods: sedimentation velocity and sedimentation equilibrium. Data analysis from either method uses computer programs developed around fundamental equations. Velocity sedimentation is used to check for impurities and also to characterise molecular interactions. Equilibrium sedimentation is not used as widely, but it is used to provide first‐principle insights into intermolecular interactions such as macromolecular binding and thermodynamic nonideality.

Key concepts:

Sedimentation velocity provides information about the size and shape of molecules in solution.

Sedimentation equilibrium provides information about the interactions of macromolecules in solution.

The quaternary structure of a molecule may be determined under different solvent conditions.

Mass‐action equilibria may be characterised with respect to the stoichiometry and association energies.

Sedimentation velocity analysis is used to detect aggregates and fragments of highly purified molecules.

Thermodynamic nonideality may be characterised from sedimentation equilibrium analysis.

Analysis programs for sedimentation velocity data often use solutions of the Lamm equation.

Analysis programs for sedimentation equilibrium data are based on thermodynamic first principles.
ATP
‐binding Motifs
Authors: Matte Allan , Delbaere Louis TJ 
Published: April 2010

Abstract

Adenosine 5′‐triphosphate (ATP) binds to a great number of proteins to elicit a wide variety of effects, including energy production and molecular signalling. Proteins have evolved different strategies to specifically recognize ATP, utilizing different ways of binding the phosphoryl moieties as well as the adenine base. The most common, conserved sequence and structural motif for binding ATP is the Walker‐A motif, or P‐loop, found in many different protein structural families. Greater variation in the sequence of the P‐loop is being recognized, as more ATP‐binding proteins are being structurally and functionally characterized. In contrast to the P‐loop, recognition of the adenine base often makes use of conserved structural motifs of main‐chain atoms via hydrogen‐bonding interactions, or side‐chains in stacking interactions, without a definitive amino acid sequence pattern.

Key concepts:

A major class of ATP‐binding proteins are those that contain a P‐loop or Walker‐A motif.

P‐loops or glycine‐rich loops function by binding the phosphoryl groups of ATP.

Several sequence variations on the Walker‐A motif are now known and have been functionally characterized.

The Walker‐B motif contains a conserved acidic residue (Glu/Asp) that functions to bind directly or indirectly a metal ion important in catalysis.

Adenine‐binding does not occur through specific sequence motifs, but rather uses a conserved pattern of polar and nonpolar interactions within a structural motif.

Both main‐chain hydrogen bonding and aromatic residue stacking contribute to adenine‐binding by proteins.
Genetic Counselling: Psychological Issues
Authors: Biesecker Barbara B 
Published: April 2010

AbstractThe goals of genetic counselling vary according to the setting in which clients are seen, from prenatal to adult. Yet an important universal goal of genetic counselling is to address the psychological impact of a genetic diagnosis, risk or test result. Clients experience a range of genetic conditions and risks that may elicit grief, conflict, sadness, relief, guilt, uncertainty and ambivalence. The specific needs of genetic counselling clients are shaped by the degree of health threat they perceive, and by their personality traits, background, resources and prior experiences. Characteristics of the condition coupled with perceptions of its burden contribute to the quality of life experienced by clients. How well genetic counselling meets clients’ needs in enhancing quality of life is determined by the expert skills of counsellors to assist clients in using their own psychological assets to adapt to their circumstances.Key conceptsGenetic counselling aims to help clients adapt to living with a genetic condition or risk.Genetic counselling clients’ experience genetic conditions or risk according to their own illness perceptions and this predicts their overall quality of life.
DNA
Methylation in Development
Authors: Rutledge Charlotte E , Lees‐Murdock Diane J , Walsh Colum P 
Published: April 2010

Abstract

DNA (
deoxyribonucleic acid
) methylation is an epigenetic modification which can silence gene expression and stabilize repeats. A methyl group is added to cytosine when followed by guanine (CpG) and CpGs are enriched at the promoters of many genes and in retrotransposons. Nevertheless, only a small number of these CpG‐rich genes are actually regulated by methylation. These fall into three classes: imprinted genes, genes on the inactive X and germ cell‐specific genes. Methylation is reprogrammed (erased and re‐established) at two points during development: around implantation and the during germ cell development.
DNA methyltransferase 3a
(
DNMT3A
) and
DNMT3B
establish methylation patterns, with the help of the cofactor
DNMT3L
in the germ cells, then
DNMT1
maintains them during mitotic division. Failure of either process leads to developmental defects, sterility or embryonic death. Histone methylation and small RNAs (
ribonucleic acids
) have been implicated in directing the
methyltransferases
to particular genes or repeats.

Key concepts:

DNA methylation is associated with transcriptionally inactive chromatin and helps stabilize it.

Methylation in mammals occurs exclusively at cytosine followed by guanine (CpG).

CpG‐rich regions (CpG islands) are found at the start of many genes and in retrotransposons.

Methylation of CpG islands maintains repression on imprinted genes, genes on the inactive X chromosome, germ cell‐specific genes and certain retrotransposons.

Three key enzymes are involved, DNMT1, DNMT3A and DNMT3B, together with the cofactor DNMT3L.

DNMT1 maintains DNA methylation on all sequences during development.

DNMT3A and DNMT3L are essential for imprinting and retrotransposon repression in the germ cells.

There is a developmental cycle of changes in the level of genomic methylation, which is necessary for the correct reprogramming of imprinted and X‐chromosome genes for the next generation.

Evidence is growing that histone modifications determine which DNA sequences become methylated.
Phytophthora
Authors: Whisson Stephen C 
Published: April 2010

Abstract

Diseases of plants caused by species of the genus

Phytophthora

represent some of the most devastating diseases of crops worldwide. All known species of

Phytophthora

are plant pathogens. Although superficially similar to filamentous fungi, the

Phytophthora

species belong to the class oomycetes, and are more closely related to brown algae.

Phytophthora

‐incited disease may be controlled by genetically encoded resistance in the host plants. In cases where no host plant resistance to

Phytophthora

disease is available, application of control chemicals may be successful in controlling disease, although intensive chemical control is potentially environmentally damaging. Much recent research into

Phytophthora

biology has utilised modern molecular biology techniques. DNA (
deoxyribonucleic acid
) sequencing of three

Phytophthora

genomes has revealed an extraordinary repertoire of genes encoding proteins secreted by

Phytophthora

for the purpose of overcoming and subverting host plant innate and active defence responses, indicating pathogenicity in this genus to be a highly complex process.

Key Concepts

Species of
Phytophthora
cause some of the most destructive plant diseases known.

Phytophthora
species resemble fungi, but are phylogenetically distinct.

Some
Phytophthora
species have coevolved with their hosts, leading to a gene‐for‐gene system of matching plant resistance and
Phytophthora
avirulence gene products.

Some, but not all,
Phytophthora
diseases may be controlled by resistance in the host plant, or through the application of control chemicals.

Phytophthora
species secrete a complex array of proteins, including effectors, during invasion of plant tissues, some of which act to suppress plant defence responses.

Some effectors may be recognised by host plants, leading to resistance.

Other effectors may be required for pathogen growth and development during infection.

Numerous secreted
Phytophthora
proteins exhibit evidence of selection pressure from their plant hosts.
Counselling Issues around Preimplantation Genetic Diagnosis (
PGD
)
Authors: Ross Sarah 
Published: April 2010

Abstract

Preimplantation genetic diagnosis (PGD) is a highly specialized process which involves using assisted reproductive techniques for a couple to increase their chances of having a child that is unaffected by a serious known genetic disorder. It requires a multidisciplinary team of professionals comprising specialists in both assisted reproduction and genetics.
Before a decision by a couple to undergo PGD treatment, the counsellor needs to assess their situation, discuss their genetic risk and the process of PGD including the advantages and disadvantages while taking into account the emotional, practical and financial issues. This should enable the couple to make an informed decision about whether PGD is the most appropriate treatment for them. Counselling opportunities arise during and after a treatment cycle ensuring that couples are supported and fully aware of the implications of decisions that need to be made at each stage of the process.

Key concepts:

Preimplantation genetic diagnosis involves using assisted reproductive techniques to obtain embryos which are then tested for a known genetic condition, before transfer to the uterus.

Assisted reproductive techniques used in PGD involve artificially stimulating the ovaries to release large numbers of eggs which are collected and then fertilized using
in vitro
fertilization (IVF) or intracytoplasmic sperm insertion (ICSI).

Genetic counselling is a communication process that is associated with the occurrence or risk of a genetic disorder in the family.

FISH analysis – fluorescent
in situ
hybridization is a cytogenetic technique used to detect and localize the presence or absence of specific DNA sequences on chromosomes. It uses fluorescent probes that bind to those parts of the chromosome that show a high degree of sequence similarity.

Preimplantation genetic haplotyping (PGH) involves taking a single cell and extracting DNA, which is then amplified before being used for DNA fingerprinting. PGH can be used where the exact mutation is not known or cannot be identified, as the technique scans for the presence of the genetic haplotype, which is associated with the familial disease gene region.
Small
RNA
s in Neurological Disorders
Authors: Lin Li , Vitale Angela V , Jin Peng 
Published: April 2010

Abstract

Small RNAs (
ribonucleic acids
) are a group of noncoding RNA molecules with modulation functions that span a broad range, from RNA modification to protein synthesis regulation. The expression of small RNAs is found to be widespread in all eukaryotes, and more than a third of protein‐coding genes in the human genome are regulated by small RNAs. Mounting evidence suggests that the appropriate spatiotemporal expression of small RNAs, in particular microRNAs (miRNAs), is required for both brain morphogenesis and nervous system development. Moreover, dysregulation of specific miRNAs is possibly correlated with the pathogenesis of neurodevelopmental disorders. Understanding the potential roles of small regulatory RNAs in neural development and various human neurological disorders could reveal therapeutic applications that involve restoring or inhibiting the function of small RNAs.

Key Concepts:

Small RNAs have been found in all major groups of eukaryotes.

Small RNAs are divided into four classes: microRNAs, small interacting RNAs, Piwi‐interacting RNAs and small nucleolar RNAs.

In humans, microRNAs play important functional roles, interacting with at least 30% of all mRNAs.

MicroRNAs are highly involved not only in normal brain function, but also in many developmental disorders.

Known to act on mRNAs, microRNAs will degrade, translationally inhibit or even upregulate mRNA expression.

One microRNA can affect the course of several neurodevelopmental disorders.

A full understanding of microRNA function will yield possible medicinal treatments.
Genetic Basis of Monogenic Forms of Parkinson Disease
Authors: Brockmann Kathrin , Gasser Thomas 
Published: April 2010

Abstract

There has been a plethora of genetic findings in Parkinson's disease (PD) during the last decade, and mutations in an increasing number of genes are found to cause monogenic forms of this disorder. To date, we know of 15 gene loci (PARK1–15) causing either autosomal dominantly or autosomal recessively inherited forms of PD. Proteins encoded by PD‐associated genes play important roles in different cellular functions and partially interact with each other suggesting that they share common pathways that lead to neuronal degeneration. At least some of these genes may also play a direct role in the aetiology of sporadic PD, and therefore it seems likely that the cellular pathways identified in familial variants of the disorder also elucidate the molecular pathogenesis in the sporadic form.
Recently, these genetic findings have begun to impact clinical practice. Here, we highlight these genetic advances, and discuss their importance for clinical practice.

Key Concepts:

Since both, monogenic and sporadic forms of PD, tend to share many overlapping features that include, most importantly, parkinsonism with nigrostriatal dopaminergic degeneration genetic findings imply common pathogenic mechanisms and may provide new insights in the specific molecular pathways underlying PD.

Since α‐synuclein was found to be the major component of Lewy bodies in familial and sporadic cases aggregation of this protein is thought to be a crucial step in dopaminergic neurodegeneration in both,
SNCA
‐linked as well as sporadic PD.

LRRK2
represents the most frequent form of autosomal dominantly inherited late‐onset PD offering the possibility to study the development of the disease in a sizeable population.

Presumption is rising that
parkin
,
PINK1
and
DJ‐1
which are associated with autosomal recessive forms of PD may act in a common pathway and that mutations within one of these genes imply ‘loss‐of‐function mechanism’ leading to cell death underlying mitochondrial and proteasomal dysfunction.

Longitudinal studies in presymptomatic mutation carriers may reveal pre‐motor changes by clinical, biochemical or imaging methods, indicating the very early phases of neurodegeneration. Therefore, further research in this population exploring neuroprotective or preventive measures are most promising to yield first results.
Deconstructing Gene Function throughENUMutagenesis
Authors: Acevedo‐Arozena Abraham , Ricketts Thomas , Corrochano Silvia 
Published: April 2010

AbstractA great majority of genes present in the human genome are also present in the mouse, thus making it an attractive mammalian model organism to study gene function and dysfunction. Over the past few decades, the ability to manipulate the mouse genome has been developed in a variety of ways, including the ability to delete genes or introduce more subtle single mutations. A complementary methodology to create mutations in the mouse is to use chemical mutagenesis.N‐ethyl‐N‐nitrosourea (ENU) is the mutagen of choice for creating random point mutations throughout the genome in many model organisms. ENU mutagenesis is a powerful hypothesis‐generating approach currently being exploited to create new mouse models through both forward and reverse genetics approaches.Key Concepts:ENU produces mainly point mutations randomly throughout the genome.ENU mutagenesis can be used in both forward and reverse genetics approaches.ENU phenotype‐driven screens do not require previous knowledge of the gene to create new mouse models.ENU phenotype‐driven screens identify new mouse models by means of phenotyping.
Genetics of Personality Disorders
Authors: Reichborn‐Kjennerud Ted 
Published: April 2010

AbstractEvidence from family, adoption and twin studies indicate that genetic factors significantly influence liability to personality disorders and contribute to the co‐morbidity between personality disorders and between personality disorders and other psychiatric disorders. Molecular genetic studies aiming at identifying specific genes have been applied, to a limited extent, to personality. Significant associations have, however, been found with candidate genes related to neurotransmitter pathways, especially in the dopaminergic or serotonergic systems. Both quantitative and molecular genetic studies indicate that gene–environment correlation and interaction play a role in the aetiology of personality disorders. Methods like genome‐wide association studies, analyses of copy‐number variation, studies of rare genetic variants and epigenetic methods have not yet been applied to personality disorders, but will hopefully contribute to our future understanding of the causal mechanisms involved.Key Concepts:Personality disorders are significantly influenced by genetic factors.Co‐morbidity between personality disorders and between personality disorders and other mental disorders are significantly influenced by shared genetic liability.Candidate gene association studies indicate significant relationships between personality disorders and genes related to neurotransmitter pathways, especially in the dopaminergic or serotonergic systems.Both quantitative and molecular genetic studies suggest that gene–environment interplay is involved in the aetiology of personality disorders.
Molecular Genetics of Anxiety
Authors: Sipilä Tessa , Hovatta Iiris 
Published: April 2010

Abstract

Anxiety is a normal response to a threatening situation. When anxiety is excessive and disturbs daily life and functioning, it can be diagnosed as an anxiety disorder. Anxiety disorders are typical complex disorders that are triggered by environmental factors in genetically susceptible individuals. Genetic variants in many genes have been shown to predispose to anxiety disorders, but the results have been difficult to replicate, most likely due to a small effect size of individual variants. Anxiety is an evolutionarily conserved response, and can therefore be fairly reliably modelled in rodents. Quantitative trait locus mapping and functional genomics and proteomics approaches in mouse models of anxiety have led to the identification of novel genes and pathways that are involved in the regulation of anxiety‐like behaviour. Some of these genes are expected to regulate anxiety in humans as well, and variants in them might predispose to anxiety disorders.

Key Concepts:

Anxiety disorders are complex diseases triggered by environmental factors in genetically susceptible individuals.

Genetic variants that predispose to anxiety disorders have been identified by candidate gene and genome‐wide association studies.

The effect size of the identified susceptibility variants for anxiety disorders seems to be small.

Features of human anxiety disorders can be fairly well modelled in animals, and different approaches have revealed novel genes and pathways that regulate anxiety‐like behaviour.

Combined information from several approaches, including human and mouse genetics, functional genomics, proteomics, epigenetics and neuroimaging are expected to reveal molecular mechanisms that regulate anxiety.