bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Stem Cells – Basic Biological Properties and Experimental Approaches
Authors: Hatina Jiří , Fernandes Maria Inès , Hoffmann Michèle J , Zeimet Alain G 
Published: September 2013

Abstract
Cancer stem cells (CSCs) are defined as a self‐renewing and self‐protecting subpopulation of tumour cells that can differentiate into all other tumour cell types found within a tumour. They can be prospectively identified and purified, either on the basis of specific cell surface marker expression, or by virtue of their biological properties; their self‐protection has been harnessed to develop several purification strategies, for example, side population or Aldefluor assays. Other prominent biological properties of CSCs include their exclusive clonogenicity and tumourigenicity. Many of these basic biological characteristics are shared between normal and CSCs, as are multiple signalling pathways regulating self‐renewal and differentiation. Unlike normal stem cells, CSCs often seem to be distinctly less stable, dynamically modulating their stemness and differentiation according to various environmental signals and/or genetic and epigenetic changes accumulated during the carcinogenic process. This plasticity of CSCs might underlie the prominent biological characteristics of malignant tumours, especially their propensity to metastasise.

Key Concepts:

Stem cells are long‐lived and protect their genome.

Existence of long‐lived, undifferentiated and self‐protecting cells could be indirectly inferred in tumours.

Cancer stem cells express specific cell surface markers and are amenable to differential staining procedures.

Cancer stem cells frequently exploit similar signalling pathways as embryonic stem cells and normal adult stem cells.

Hypoxia activates a multifaceted stem cell programme in tumours.

Cancer stem cell phenotype can be unstable, with repeated or even ongoing differentiation and dedifferentiation.
Molecular Genetics of Bipolar Disorder
Authors: Offord James D 
Published: September 2013

Abstract

Bipolar disorder (BPD) is a disease of unknown etiology, which is a major cause of disability. The disease is characterised by oscillation between a manic state and a depressed state, and has a significant genetic component. To try to improve understanding of the disease, linkage studies and association studies have been conducted on bipolar subjects. To date these studies have yielded equivocal results. A very small number of genomic regions and genes have been identified which are associated with the bipolar disease. This small number of genes does not explain the high heritability of the disease. Using the results of these screens as starting points it should prove possible to develop a model for the underlying molecular components of BPD.

Key Concepts:

Bipolar disorder is a highly heritable psychiatric disorder where genetics are proving to be complex.

Psychiatric linkage studies have been less successful than genome wide association studies at showing involvement of genes in psychiatric disease.

Genome wide association studies can provide information about genes that are involved in a disorder.

Not all of the heritability of bipolar disorder has been explained by genetic association studies. The nature of this ‘missing heritability’ remains unclear.

Genetic modifiers are genes that can alter the phenotype caused by a mutation. These genetic modifiers may account for some of the missing heritability seen in bipolar disorder.
Secretory Immunoglobulin A
Authors: Corthésy Blaise 
Published: September 2013

Abstract

Secretory immunoglobulin A (IgA) (SIgA) is the most abundant Ig produced at the surface of mucosal membranes in mammals. These very thin and sensitive barriers are challenged by occasional pathogenic microbes as well as by permanently residing commensal bacteria. Although not the unique guardian of mucosal epithelia, SIgA is an important component of the protective function guaranteeing maintenance of homoeostasis and wellness. Topics presented in this article include: (1) mechanisms involved in local induction of SIgA via T‐cell‐dependent and ‐independent pathways; (2) structure–function relationship in SIgA; (3) immunoregulatory role of SIgA vis‐à‐vis pathogens and commensals and (4) the unexpected contribution of SIgA in diseases. Because this is the most studied mucosal environment, most of the functional characteristics of SIgA are exemplified with respect to the gastrointestinal tract.

Key Concepts:

SIgA is the most abundant immunoglobulin produced at mucosal surfaces, and it exists in secretions in polymeric forms of high and low antigenic affinity/avidity.

The presence of secretory component in SIgA confers additional features including improved stability, proper anchoring in mucus and adequate localisation for optimal functions on the antibody.

Because epithelia in the gastrointestinal, respiratory and urogenital tracts are highly sensitive to invading environmental antigens, shielding of mucosal surfaces by SIgA is crucial to the process of protection and homoeostasis.

In addition to canonical immune exclusion, SIgA is endowed with the capacity to transport immune complexes via M‐cells to underlying dendritic cells, thus inducing attenuated mucosal and systemic immune responses.

Communication between natural polyreactive SIgA‐commensal bacteria complexes and the epithelial cells lining mucosal surfaces contributes to regulate the symbiotic host–commensal relationship.

SC, by itself, via multiple glycosylation sites, displays neutralising properties against pathogen‐associated molecules. This holds true when SC is bound to polymeric IgA in the SIgA molecule.

Increasing knowledge of the multiple modes of action of SIgA provides opportunities to investigate the potential of the antibody in passive immunisation against bacteria, viruses and toxins in the clinics.
Molecular Genetics of Chediak–Higashi Syndrome
Authors: Kaplan Jerry , Ward Diane M 
Published: September 2013

AbstractChediak–Higashi syndrome (CHS) is an autosomal recessive disorder associated with the formation of enlarged lysosomes and lysosome‐related organelles (LROs) clustered near the perinuclear region of cells. Affected vesicles include lysosomes, cytolytic granules, melanosomes and platelet dense granules. The enlarged vesicles give rise to decreased bacterial killing, partial albinism, defective wound repair, impaired coagulation and neurological problems. Patients succumb to untreated recurrent bacterial infections or a lymphoma‐like infiltration into the major organs of the body. Treatment for the disorder is prophylactic antibiotics followed by bone marrow transplant although pigmentation and neurological problems persist. The mutant gene, termedLyst, responsible for CHS is present in all eukaryotes and model organisms have been utilised to try to determine the function of Lyst. The biochemical function of Lyst has not been resolved but Lyst has been proposed to be involved in regulating lysosome/LRO size by either controlling vesicle fusion or fission.Key Concepts:Chediak–Higashi syndrome (CHS) is a lethal disorder with patients succumbing to pathogen infections if not treated with antibiotics.CHS patients show multiorgan dysfunction due to enlarged lysosome‐related organelles in all cells of the body.Treatment for CHS is bone marrow transplant, although neurological problems remain.The mutant gene responsible for CHS is Lyst, a highly conserved gene present in all eukaryotes.Lyst is a member of a family of proteins, BEACH, involved in vesicle trafficking.Regulating lysosome/LRO size is important for normal cellular processes including pigmentation, coagulation, wound repair and immune function.
Analysis of Somatic Mutations in Cancer Tissues Challenges the Somatic Mutation Theory of Cancer
Authors: Satgé Daniel 
Published: September 2013

AbstractAccording to the somatic mutation theory (SMT) of cancer, somatic mutations observed in cancerous tissues directly cause malignancy. However, a close look at the experimental data and observations about human diseases show many discrepancies with the theory, including the lack of specificity of the so‐called ‘cancer genes’ that are mutated in noncancerous tissues, and not mutated in cancers; the rarity of malignancies in some genetic conditions withdeoxyribonucleic acidrepair anomalies and the high number of initial mutations in early carcinogenesis. Above all, abnormal proliferations and altered tissue architecture before specific genetic anomalies are detected strongly support the idea that the correlation between carcinogenesis and genetic modifications is more complex and probably less determining than has been theorised by the SMT. Other theories that take into account tissue architecture and microenvironment, such as the tissue organisation field theory, are promising paths towards an understanding of oncogenesis.Key Concepts:Initial somatic mutations are found in cancer tissues much more frequently than expected from a random event.Proliferative and architectural anomalies are observed in organs before genetic anomalies occur.Mutations of the so‐called ‘cancer genes’ are present in noncancerous tissues.Mutations of so‐called ‘cancer genes’ are not present in all cells of a cancer/tumour.Tissues maintain their respective phenotypes despite many mutations.Some conditions with DNA repair deficiency have no increased risk of cancer, and some others appear to be protected against particular cancer types.Cancers can be induced by transplanting a normal tissue into an unusual environment for that tissue.Cancer cells can be reverted to normal cells when implanted into a microenvironment that is normal for this type of cells.
An Overview of Cytokine Regulation of Inflammation and Immunity
Authors: Meager Anthony , Wadhwa Meenu 
Published: September 2013

AbstractThe defence of an organism depends on the recognition of harmful stimuli followed by appropriate activation of innate and adaptive immune responses. Primary recognition of harmful stimuli is mediated by specific receptors of monocytes, macrophages and dendritic cells, leading to cytokine production. Several cytokines have proinflammatory actions that drive the innate immune response, cause inflammation and activate adaptive immune responses. Further activation of adaptive immunity depends on cytokine regulation of T‐cell differentiation into specific T‐cell subsets with specific roles in defence against the invading pathogens. Although cytokine regulation of inflammation and immunity is crucial for protection against infection and injury, their actions in excess are associated with a variety of autoinflammatory and autoimmune diseases.Key Concepts:Cytokines are a broad class of biologically active proteins with hormone‐like actions that are produced in response to homoeostatic, and more particularly harmful, stimuli.The extent of cytokine production is dependent both on the nature of the stimulus and on regulatory intracellular mechanisms.Cytokines may act on any cells that bear receptors, by which, with the involvement of signal transduction pathways, nuclear gene transcription is activated.Many cytokines act on cells of the immune and vascular systems to regulate cell proliferation, differentiation and activation of pro‐ or anti‐inflammatory mechanisms.Monocytes, macrophages and dendritic cells bear ‘pattern recognition receptors’ and are especially sensitive to harmful stimuli such as pathogens bearing ‘pathogen‐associated molecular patterns (PAMPs)’.Monocytes and macrophages produce the proinflammatory cytokines, for example, interleukin‐1, tumour necrosis factor‐α, responsible for inflammatory reactions and innate immune responses.Cytokines such as interleukin‐12, interleukin‐18 and interleukin‐23 couple the innate immune response to adaptive immune responses mediated by T cells, B cells and natural killer cells.T‐cell differentiation into specific T‐cell subsets is governed by several cytokines, for example, interleukin‐4 and interferon‐gamma, acting antagonistically to one another.Excessive cytokine production or action leads to acute or chronic inflammation, which may trigger autoinflammatory and autoimmune diseases in the long term.
Molecular Genetics of Skeletal Muscle Channelopathies
Authors: Durran Siobhan CM , Matthews Emma , Hanna Michael 
Published: September 2013

Abstract

The skeletal muscle channelopathies are disorders of muscle excitability due to disruption of the normal functioning of skeletal muscle ion channels. Such disruption to excitability can manifest clinically as episodic muscle weakness or myotonia resulting in a number of disorders classified as periodic paralysis and nondystrophic myotonias. Significant overlap is observed between these disorders in terms of both symptoms and causative genes. More than 200 mutations have been identified overall within the skeletal muscle voltage‐gated ion channel genes, with the main causative genes including
CLCN‐1
,
SCN4A
and
CACNA1S
. However, ∼20% of patients have no genetic diagnosis despite a strong phenotype. Genetic research and functional analysis of mutations together have advanced our understanding of molecular disease mechanism as well as providing new insights into normal ion channel function.

Key Concepts:

Voltage‐gated ion channels are transmembrane proteins which selectively conduct ions across the plasma membrane on activation through a change in the membrane potential.

Skeletal muscle channelopathies are caused by mutations located in functionally important areas of voltage‐gated ion channels.

Symptoms manifest as intermittent alterations of skeletal muscle function.

A number of different ion channels are known to cause the same disorders resulting in genetic heterogeneity.

Mutations in the ion channels result in disruption of the sarcolemma membrane potential, which can cause myotonia through increased excitability or periodic paralysis due to decrease excitability.

Symptoms of myotonia can be the result of mutations in either
CLCN‐1
or
SCN4A
, whereas periodic paralysis is caused by mutations in
CACNA1S
,
SCN4A
,
KCNJ2
or
KCNJ18
.

Phenotypic variability is seen even amongst patients within a single family.

Significant symptom overlap occurs between disorders, which can lead to diagnostic confusion.
Molecular Genetics of Nasopharyngeal Carcinoma
Authors: Lun Samantha Wei‐Man , Cheung Chartia Ching‐Mei , Chow Chit , Chung Grace Tin‐Yun , Lo Kwok‐Wai 
Published: September 2013

Abstract

Nasopharyngeal carcinoma (NPC) is a distinctive type of squamous cell carcinoma of the head and neck region with remarkable ethnic and geographic distribution. It is consistently associated with Epstein–Barr virus (EBV) infection and serves as a fascinating model to understand the complex interaction among environmental, viral, and genetic factors in human tumourigenesis. The development of NPC involves clonal expansion of EBV‐infected cells and cumulative genetic and epigenetic changes. Both viral and cellular genes contribute to disease pathogenesis and their interplay creates distinct phenotypes, unique molecular features and tumour microenvironment. Recent findings on EBV‐encoded and cellular miRNAs demonstrate their importance in NPC progression by altering multiple cellular pathways. On the basis of current knowledge, we proposed a stepwise model describing the initiation events and the role of EBV latent infection and multiple genetic changes in NPC tumourigenesis.

Key Concepts:

Nonkeratinising NPC is consistently associated with EBV infection.

The development of NPC involves EBV latent infection and cumulative genetic and epigenetic changes influenced by predisposing genetic factors and environmental carcinogens.

Inactivation of tumour suppressor genes at chromosomes 3p and 9p and clonal expansion of EBV‐infected cells are critical initiation events in NPC tumourigenesis.

EBV‐encoded and cellular miRNAs contribute to the NPC progression by altering multiple cellular pathways and modulating EBV latent gene expression.

The interplay between viral and cellular genes contributes to the establishment of distinct phenotypes, unique molecular features and tumour microenvironment of NPC.
Reconstruction of the Ancestral Xenarthran Karyotype
Authors: Svartman Marta 
Published: September 2013

AbstractXenarthra is the group of mammals that reunites anteaters, armadillos and sloths. According to the most recent phylogenetic schemes, Xenarthra is considered one of the four main supraordinal eutherian clades. This group, found in Central and South America, is considered especially important as it may be at the base of the eutherian tree. Although most cytogenetic studies in Xenarthra have been restricted to a few specimens and poor resolution techniques, recent chromosome painting analyses in some Xenarthra species resulted in important data regarding mammalian karyotypic evolution. An ancestral karyotype with 2n=48 chromosomes has been recently proposed as ancestral to all Xenarthra. This complement is very similar to the 2n=46 proposed as ancestral to all eutherian mammals, which may be a further indication of the basal phylogenetic position of Xenarthra in the eutherian tree.Key Concepts:Xenarthra is a Central and South American group of mammals represented by anteaters, armadillos and sloths.Xenarthra is phylogenetically important because of its likely basal position in the tree of eutherian mammals.In general, cytogenetic data on Xenarthra are restricted to a few specimens and to low resolution techniques.However, the recent use of molecular cytogenetics, namely chromosome painting, in Xenarthra has provided data that allowed the reconstruction of a hypothetical Xenarthra ancestral karyotype (XAK) with 2n=48.The 2n=48 XAK closely resembles the proposed ancestral eutherian karyotype (AEK) with 2n=46, which further supports the idea that Xenarthra is basal to all eutherians.
Molecular Genetic Causes of Discordance in Monozygotic Twins
Authors: Czyz Witold , Ramagopalan Sreeram V 
Published: September 2013

AbstractAlthough monozygotic (MZ) twins arise from the same gametes and a single zygote, they can at times reveal molecular genetic discordance. Differences in ploidy, chromosomal rearrangements and structural anomalies as well as different copy number variations (CNVs), point mutation discordance and genetic mosaicism have all been documented in MZ siblings. Depending on the type and magnitude, genetic discordance may lead to markedly different phenotypes. Traditionally, the best‐evidenced type of discordance encompasses a range of chromosomal abnormalities, partly due to their significant multiple effects on a phenotype. In contrast, surveying for single nucleotide polymorphism and CNV discordance globally poses more challenges. In the recent decades, growing evidence for low‐level CNV and point mutation discordance as well as mosaicism has amassed, although their frequency and phenotypic significance are yet to be established. High‐throughput sequencing strategies are likely to provide answers.Key Concepts:Despite stemming from the same zygote, monozygotic twins may develop genetic discordance.Postzygotic genetic alterations often result in genetic mosaicism in one or both of the twins.Confirmed genetic discordance in MZ twins encompasses mainly known disorders with clear or multiple/global effects, including five extremely rare cases of point mutations responsible for monogenic disorders and a range of chromosomal abnormalities as well as a few cases of trinucleotide repeat disorder discordance.The most common type of genetic discordance in MZ twins are aneuploidies, particularly 45,X0 monosomy and, to a lesser degree, trisomies 21, 15 and 13, whereas discordance for structural rearrangements is even less frequent.In MZ twins affected by aneuploidies, somatic mosaicism often plays a critical role in phenotypic discordance.Genome‐wide studies of SNP and CNV discordance in twins face technical difficulties and have not yet brought a definite answer, although there is limited evidence for very low‐level discordance.It will be challenging to fully ascertain the magnitude of genetic discordance in twins due to possible small‐scale SNP and CNV mosaicism across different tissues.
Genetics of Depression
Authors: Hodgson Karen , McGuffin Peter 
Published: September 2013

Abstract
Probing the genetic basis of depression not only informs our understanding of the role that genes play in disease, but also further offers the potential to provide invaluable insights into the aetiology, classification and neurobiology of the disorder. Moreover, understanding the genetics of depression may offer a starting point for the development of novel, and potentially more efficacious treatments for patients.
Although a number of genes have been implicated in depression, a genetic variant that is unequivocally associated with an increased risk of the disease is yet to be identified. As genome‐wide approaches to analysing genetic variation gain momentum, large‐scale collaborations have brought insights into how best to conceptualise depression as an illness. Nonetheless, the identification of specific genetic variants associated with depression still eludes researchers. By building on the knowledge gained from these collaborative datasets, and utilising newer and more sophisticated technologies and methodologies, it is likely that researchers will be able to replicate in depression, the successes of genetic research in other complex disorders.

Key Concepts:

MDD is a complex genetic disorder involving interactions between multiple genetic variants and environmental factors.

Some areas of interest have been implicated via linkage methodologies in MDD, but this method is more suited to more strongly heritable forms of the disease.

Many candidate gene studies of MDD have been underpowered to detect small genetic influences, and are constrained by our limited understanding of the neurobiology of the disease.

Genome‐wide association methodologies have not yet identified any clear markers of the disease, but have informed our understanding of MDD.

Following the progress of genetic research into other disease phenotypes, the collection of larger patient cohorts is likely to yield success in identifying the genetic variants involved in MDD.

Newer technologies and analysis methods to model the biological complexity of the illness are also rapidly evolving.
Weiss, Paul Alfred
Authors: Brauckmann Sabine 
Published: September 2013

AbstractPaul A. Weiss (1898–1989), born and educated in Vienna (Austria), first studied the movements of butterfly wings. He argued that the locomotion patterns arrange a network system of behaviour, which controls as a whole the future movements. By transplantation and tissue culture experiments he studied the issue as to how motor nerves succeed in moving the correspondent muscle. The data he explicated with the resonance principle, stating that the nerve and the muscle are attuned to each other by electroacoustic signals. Until 1950, he discovered the axonal transport of peripheral nerves and invented a new surgical technique to bridge cut nerves without sutures. In developmental biology, he explained the mechanisms of cell contact and investigated the self‐sorting of embryonic cells, a precursor of modern stem cell research. In 1960, Weiss and his collaborators produced a media event when demonstrating that cell suspensions have the ability to reconstitute complete body organs. Further, they improved the experimental tools of phase contrast microscopy, time‐lapse motion films and tissue cultivation. Weiss' experimental work had a strong impact on the progress of developmental, cell and neurobiology in the twentieth century, and influenced the newly forming disciplines of cell biology and the neurosciences.Key Concepts:The concept of contact guidance improved Cajal's doctrine of neurotropism.Experimental data demonstrated axonal flow in the 1940s, but were not accepted until the 1960s.Experiments on cell sorting and cell suspensions are precursors of modern stem cell research.The disciplination of the neurosciences was delayed by the resistance of (medical) neurophysiology.Prematurity prevents the acceptance of experimental data, regardless of being correct.