bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological/Biochemical Features and Molecular Genetics of Specific Language Impairment (
SLI
)
Authors: Caylak Emrah
Published: April 2013

Common learning disorders include attention‐deficit hyperactivity disorder, dyslexia, specific language impairment (SLI), speech–sound disorder and dyspraxia. They are influenced by genes and several research groups to attempt to identify susceptibility genes of learning disorders through the sequential analysis of genetic linkage and association. This review highlights the genetic contribution to SLI and the current molecular genetic researches aimed at identifying susceptibility and candidate genes for SLI. Currently, four susceptibility loci and three candidate genes (
CMIP
,
ATP2C2
and
CNTNAP2
) associated with SLI have been found. This review also summarises the biological/biochemical features of SLI. The success of dietary intervention of nutritional supplements (i.e. thiamine and some fatty acids) to improve learning abilities in SLI and dyslexia suggests that a greater understanding of biochemical abnormalities may provide a useful addition with other treatment procedures for these learning disorders.

Key Concepts:

Learning disorders may cause the learner to receive and process some information inaccurately. People with learning disorders may have problems of basic psychological processes involved in understanding or in using language, spoken or written, that may manifest itself in an imperfect ability to listen, think, speak, read, write, spell or do mathematical calculations.

Individuals with specific language impairment (SLI) seem to have problems in pragmatics, such as discourse maintenance, use and range of speech acts and narrative abilities.

Genetic factors are important in specific language impairment.

Molecular genetic researches should be aimed to identify susceptibility genes for SLI.

Molecular advances in SLI will help to set the research agendas for future studies to follow.

The association and linkage studies of learning disorders may help us to understand the biological basis of normal learning variation, and shed light on more fundamental questions regarding the origin of human speech and language.
Lipid Rafts
Authors: Germain Véronique , Perraki Artemis , Mongrand Sébastien
Published: April 2013

The knowledge about the structure of the biological membrane changed during the last 70 years. In the 70s, Singer and Nicholson proposed the fluid mosaic model, a major conceptual breakthrough in which amphiphilic proteins reside within the lipid bilayer. In this dynamic structure, components can move laterally. Further works led to major modifications of this model. Indeed, functional aspects of trafficking and signal transduction suggested that lipids and proteins do not distribute randomly but can be sequestered in small domains, thus enhancing protein–protein interactions and speeding up signal transduction and enzyme activity. The ‘raft hypothesis’ was born. Rafts are small and transient microdomains enriched in sphingolipids and sterols, together with specific proteins with important functions. This hypothesis explains the heterogeneity of the distribution of membrane proteins by a spontaneous demixing of lipids to form domains involved in signal transduction, cell trafficking and host–pathogen relationship.

Key Concepts:

Biological membranes are organised in small, dynamic and transient domains called lipid rafts.

Lipid rafts exist in all eukaryotic cells, mostly in the plasma membrane.

Lipid rafts are enriched in sphingolipids and sterols, and depleted in phosphoglycerolipids.

Lipid rafts are involved in signal transduction pathways, cell trafficking and host–pathogen relationship.
Potassium in Plants
Authors: Amtmann Anna , Rubio Francisco
Published: April 2013

Potassium (K) is an essential macronutrient for plants involved in many physiological processes. It is important for crop yield as well as for the quality of edible parts of crops, as it is also required in human nutrition. Although K is not assimilated into organic matter, K deficiency has a strong impact on plant metabolism. Plant responses to low K involve changes in the concentrations of many metabolites as well as alteration in the transcriptional levels of many genes and in the activity of many enzymes. Today, these changes can be studied with high throughput technologies that allow a quantitative description of metabolic responses to K deprivation at multiple levels. To ensure K nutrition, plant roots are endowed with high‐ and low‐affinity uptake systems, some of which have been identified and characterised over the last decades of research.

Key Concepts:

K is an essential macronutrient required for plant growth and development.

K deficiency affects many essential physiological and metabolic processes.

The K status determines the profile and distribution of primary metabolites in plant tissues.

K nutrition is closely related to sugar allocation, nitrogen assimilation and amino acid levels.

High‐throughput technologies allow researchers to determine simultaneously a large number of metabolites, transcript levels and enzyme activities in response to K supply.

K deficiency leads to build‐up of sugars, down‐regulation of nitrate uptake and synthesis of nitrogen‐rich amino acids.

Roots are endowed with high‐ and low‐affinity K uptake systems that ensure K nutrition in a wide range of external concentrations.

hak5 transporters mediate high‐affinity K uptake and akt1 channels mediate low‐affinity K uptake.

Under certain conditions akt1 channels can also mediate K uptake from very low concentrations.

Additional unidentified systems may also promote root K uptake.
Evolution of Plant
Micro
RNAs
Authors: Tamas Dalmay
Published: April 2013

Microribonucleic acids (miRNAs)
are small noncoding regulatory molecules encoded in the genome and generated through several processing steps. They recognise specific messenger RNAs and regulate their expression by cleavage or by translational inhibition. MiRNAs were only discovered approximately 10 years ago but it quickly became evident that they play an important role in development and stress responses. Initially it was thought that all miRNAs are conserved in plants because the technology only allowed to sequence the most abundant miRNAs. However, the development of next generation sequencing technologies allowed researchers to generate millions of sequencing reads in a sample, which resulted in the identification of the less abundant miRNAs. Analysis of large‐scale sequencing data revealed that the number of nonconserved miRNAs is much larger than previously thought. This review focuses on the evolution of plant
MIRNA
genes from protein‐coding genes by describing the difference between conserved and nonconserved
MIRNA
families.

Key Concepts:

MicroRNAs are small noncoding regulatory molecules.

Primary miRNA transcripts are folded into a stem–loop secondary structure, which is cleaved twice by DICER‐LIKE1 releasing the microRNA duplex.

One strand of the microRNA duplex is incorporated into an ARGONAUTE complex and guides the complex to specific mRNAs.

The ARGONAUTE complex usually cleaves the target mRNA but it also suppresses the translation of noncleaved mRNAs.

Some
MIRNA
genes are ancient and conserved in all embryophytes but there are nonconserved
MIRNA
families that are only in angiosperms or specific to monocots or dicots. A large number of
MIRNA
families are even divergent between dicot families.

New
MIRNA
genes can potentially evolve from any inverted repeats but the most evidence exists for generation from inverse duplication of protein‐coding genes followed by deletions and mutations.

Indirect evidence suggests rapid birth and death of
MIRNA
genes: approximately 1–3
MIRNA
genes per million years in the
Arabidopsis
lineage.

Nonconserved
MIRNA
genes are weakly expressed, imprecisely processed, show uniform nucleotide divergence and many lack targets, suggesting that they are evolving neutrally.

Nonconserved
MIRNA
genes could be a source of ‘regulatory diversity’, which can be selected for if they acquire target genes and that is advantageous for the plant, maybe in a new environment.
Plant Cell Division
Authors: Müller Sabine
Published: April 2013

Cell division is characterised by the segregation of genetic material and the redistribution of cellular contents facilitated by the cytoskeleton. Plant cells derive from divisions in the meristems of developing organs. However, plant cells are enclosed in rigid cell walls, unable to migrate and change their location within tissues. Thus, positions of division planes, together with successive polarised cell expansion are the major determinants of cell shape and consequently morphology of plants. The basic building blocks of the cytoskeleton, tubulins, actins and cytoskeleton associated motor‐ and nonmotor‐proteins are conserved. Yet, plants have developed unique cytoskeletal arrays and molecular mechanism to determine the division plane very early in mitosis and to facilitate the synthesis and insertion of the partitioning cell plate at the end of cell division.

Key Concepts:

Plant cells utilise specialised cytoskeletal arrays to determine the division plane early in mitosis and form a cell plate to separate daughter cells late in mitosis.

Cell geometry and nuclear position are informative for division plane selection.

The preprophase band (PPB) predicts the future division plane and recruits proteins that identify the cortical division site (CDS) throughout mitosis.

Mutants defective in PPB or CDS establishment/maintenance exhibit mispositioned cell walls and altered cell and plant morphology.

Successful cell plate formation relies on cytoskeletal reorganisation and vesicle fusion.
Genetics of Silver–Russell Syndrome
Authors: Eggermann Thomas
Published: April 2013

Human growth is a complex process and requires the appropriate interaction of many factors. Central members in the growth axes are regulated epigenetically and thereby reflect the profound significance of imprinting for correct mammalian ontogenesis. A prominent imprinting disorder associated with a disturbed imprinting is Silver–Russell syndrome (SRS), a congenital disease characterised by intrauterine and post‐natal growth retardation and further characteristic features. SRS is molecularly heterogenous: 7% of patients carry a maternal uniparental disomy of chromosome 7, >38% show a hypomethylation in the imprinting control region 1 in 11p15. Interestingly, hypermethylation of the same region is associated with the overgrowth disease Beckwith–Wiedemann syndrome (BWS), thus SRS and BWS can be regarded as genetically (and clinically) opposite diseases. Because of the different imprinting regions involved, SRS is a suitable model to decipher the role of imprinting in growth and the functional interaction between imprinted genes in different genomic regions.

Key Concepts:

Silver–Russell syndrome is a clinically heterogeneous syndrome and belongs to the group of congenital imprinting disorders.

Congential imprinting disorders show a broad spectrum of epimutations and mutations in differentially methylated regions.

Different chromosomal regions might be affected by molecular alterations in Silver–Russell syndrome, that is chromosomes 7 and 11p15.

The functional significance of the observed molecular aberrations in SRS is currently unknown.

Multilocus methylation defects are present in a considerable number of patients with imprinting disorders and indicate a general disturbance of the establishment and/or maintenance of imprinting marks.

Deciphering the molecular and functional basis for the clinical course of SRS helps to generally understand epigenetic regulation.
Molecular Genetics of Kabuki Syndrome
Authors: Micale Lucia , Merla Giuseppe
Published: April 2013

Kabuki syndrome (KS) is a rare, multiple congenital anomalies/mental retardation syndrome characterised by a peculiar face, skeletal abnormalities, cardiac anomalies, and immunological defects. Exome sequencing identified
MLL2
mutations as a major cause of KS. MLL2 is a member of the Mixed Lineage Leukaemia (MLL) family of histone methyltransferases, essential in the epigenetic control of active chromatin states. MLLs act as transcriptional co‐activators in embryogenesis and development. As a significant proportion of patients do not have any
MLL2
mutation, the existence of additional genes associated with this syndrome was postulated. By Comparative Genomic Hybridisation (CGH) array,

de novo

partial and/or complete deletions of
KDM6A
gene have been identified in a small group of
MLL2
‐mutation‐negative Kabuki patients. Notably,
KDM6A
codes a histone demethylase that interacts with MLL2. Overall, these findings suggest that Kabuki syndrome is a genetic heterogeneity disease and highlights the growing role of histone methylases and histone demethylases in multiple congenital anomalies and intellectual‐disability syndromes.

Key Concepts:

Kabuki syndrome is a rare, multiple malformation disorder characterised by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability.

Kabuki syndrome is an autosomal dominant condition that

de novo

arises in the majority of patients. It is phenotypically variable and genetically heterogeneous.

Whole exome sequencing identified mutations in
MLL2
gene in approximately 70% of the Kabuki patients.

The
MLL2
gene encodes a multiple domain‐containing protein that methylates the Lys‐4 position of histone H3 (H3K4), an epigenetic mark correlated with transcriptional active chromatin.

Approximately 70% of
MLL2
mutation‐positive KS patients carry truncating mutations predicted to result in haploinsufficiency or nonfunctional MLL2 protein.

In a search for an additional gene causing Kabuki syndrome, microdeletions of the
KDM6A
gene were identified in three
MLL2
‐mutation‐negative Kabuki patients.

KDM6A is a histone demethylases that interacts with MLL2.

Histone methylases and histone demethylases are key‐genes involved in multiple congenital anomalies and intellectual‐disability syndromes.
Germline Copy Number Variation and Cancer Risk
Authors: de Voer Richarda M , Venkatachalam Ramprasath , van Kessel Ad Geurts , Kuiper Roland P
Published: April 2013

Cancer is usually considered to be an acquired disease caused by the progressive accumulation of somatic
deoxyribonucleic acid (DNA)
changes. It is clear, however, that inherited factors may also play a significant role in the initiation of this disease. Some of these factors represent loss‐of‐function mutations in tumour suppressor genes, resulting in an increased cancer risk among carriers. Such an increased risk may also be attributed to the presence of multiple polymorphic variants such as single nucleotide polymorphisms (SNPs), each of which may convey a mild effect upon cancer susceptibility. DNA copy number variation (CNV) and other structural variations in the human genome are increasingly recognised as an alternative source of genetic variation that may influence cancer risk. Specifically, rare CNVs may affect important cancer‐associated genes and/or pathways and, thus, provide an explanation for moderate‐ to high‐risk cancer families. Therefore, it is anticipated that the identification of rare germline CNVs in unexplained familial and early onset cancer patients will contribute to our understanding of cancer predisposition and development.

Key Concepts:

Copy number variation (CNV) is a common form of normal variation affecting a significant proportion of the human genome.

CNVs frequently encompass annotated genes.

Disruption and/or silencing of critical genes located in rare CNVs may result in increased risk of disease, including cancer.

Genome‐wide copy number analysis can be used as a strategy to identify novel moderate‐ to high‐penetrant cancer predisposing genes and/or mechanisms.

Discovery of cancer‐predisposing CNVs may reveal new cancer syndromes that exhibit additional clinical features.
Molecular Genetic Basis of Myotonic Dystrophy
Authors: Radvanszky Jan , Kadasi Ludevit
Published: April 2013

Myotonic dystrophy (DM) comprises at least two genetically distinct forms, both of which are caused by expansions of microsatellite repeats. Expansion of a CTG repeat in the
DMPK
gene leads to DM1, whereas expansion of a CCTG repeat in the
ZNF9
gene causes DM2. In both cases, the repeat units may expand to several thousand repeats. Strikingly similar phenotypes, mutation types and pathological findings suggest a common pathogenic mechanism for both DM1 and DM2. However, the differences between DM1 and DM2 may be a consequence of locus‐specific effects involving haploinsufficiency of different genes and downstream events triggered by CUG or CCUG transcripts. Altogether, the complex DM1 and DM2 phenotypes are probably caused by specific combinations of several possible pathogenic pathways in different tissues of individual patients.

Key Concepts:

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are complex multisystemic disorders with highly similar but not identical symptoms.

Both DM1 and DM2 are caused by expansions of microsatellite repeats, however, in two distinct genes (
DMPK
and
ZNF9
).

Mechanisms leading to the DM1 and DM2 symptoms are very complex with several possible pathogenic pathways.

The best described pathogenic pathway involves the misregulation of two alternative splicing regulators, CUG‐BP1 (gain of function) and MBNL1 (loss of function), leading to target‐specific splicing alterations.

Both CUG‐BP1 and MBNL1 are multifunctional proteins; thus, their activation/sequestration have effect on further cellular functions such as transcription, translation and mRNA decay.

Both DM1 and DM2 causing expansions can also lead to decreased levels of proteins coded by genes around and near to the expansion sites, such as
DMPK
,
ZNF9
,
SIX5
and
DMWD.

The exact molecular pathogenic mechanism in certain tissues is probably not uniform, it rather represents a specific combination of several distinct pathogenic pathways.
Implications ofRNA‐binding Proteins for Human Diseases
Authors: Lukong Kiven E , Fatimy Rachid El
Published: April 2013

RNA‐binding proteins play pivotal roles inribonucleic acid (RNA)metabolism. The identification of mRNA targets of RNA‐binding proteins has also contributed to the delineation function of these proteins. The different tissue specificity and subcellular localisation of the RNA‐binding proteins show that these proteins can regulate specific aspects of mRNA processing and function in cells, from splicing and transport to translation and stability. Mutations, deletions and/or autoimmune reactions affecting RNA‐binding proteins lead to alterations in cellular processes, normal development and various disorders. The vast majority of these diseases are neurological or neuromuscular disorders and includes myotonic dystrophy, spinal muscular atrophy, oculopharyngeal muscular dystrophy, amyotrophic lateral sclerosis, fragile X syndrome, fragile X associated tremor/ataxia syndrome and paraneoplastic opsoclonus‐myoclonus ataxia. Altered expression of RNA‐binding proteins is also a common feature in various cancers. Understanding the molecular mechanisms of RNA‐binding proteins aberrations in disease could lead to better‐targeted therapies.

Key Concepts:

RNA‐binding proteins are key components in RNA metabolism.

RNA‐binding proteins contain modular amino acid sequences that mediate RNA binding.

The two largest RBP families contain the RNA recognition motif (RRM) and the K homology (KH) domains.

Deleterious RNA‐dominant loss‐of‐function or gain‐of‐function mechanisms are associated with defects in RBPs.

Several neurological and neuro‐muscular diseases are linked to defects in RBPs.

FXS is caused by CGG repeat in the 5′ untranslated region of theFMR1gene.

Antibodies against RBPs Hu and Nova are implicated in the pathogenesis of paraneoplastic neurologic syndromes.

DM1 is associated with the accumulation of RNA aggregates and misregulation of the RBPs, MBNL1 and CUGBP1.

Translocations of genes encoding RBPs and aberrant expression RBPs have been associated with various cancers.
Molecular Genetics of Myelodysplastic Syndromes
Authors: Bejar Rafael , Steensma David P
Published: April 2013

Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic disorders characterised clinically by inefficient haematopoiesis, cytopenias of the peripheral blood and a risk of progression to acute myeloid leukaemia (AML). Molecularly, MDS can be associated with a wide range of acquired chromosomal abnormalities, epigenetic alterations and single gene mutations. These abnormalities affect diverse molecular pathways includingribonucleic acid(RNA) splicing machinery, epigenetic modifiers, haematopoietic transcription factors, receptor tyrosine kinase signalling, cell cycle regulation and apoptosis. The particular combination of somatic genetic lesions in any given patient will influence how their disease is manifested, and together with individual background germline genotype may explain much of the clinical heterogeneity associated with MDS. Here, the common genetic abnormalities that underlie MDS and how these abnormalities influence the development and progression of these disorders have been reviewed.

Key Concepts:

MDS represent a collection of disorders marked by abnormal, inefficient haematopoiesis, cytopenias of the peripheral blood and a predisposition for progression to AML.

Like other haematopoietic malignancies, MDS arise from the clonal expansion of a single, abnormal haematopoietic cell.

The abnormal MDS cells that maintain the disease have the ability to self‐renew and clonally expand because they have a selective growth advantage compared to their normal counterparts.

Impaired haematopoietic differentiation in MDS can lead to cytopenias or to the production of terminally differentiated cells with abnormal function.

A combination of somatic genetic abnormalities (acquired changes to thedeoxyribonucleic acid(DNA) coding sequence), epigenetic abnormalities (heritable changes in gene expression) and marrow microenvironmental abnormalities contribute to the development and progression of MDS.

Approximately, 50% of MDS cells have a chromosomal abnormality detectable by routine metaphase karyotype analysis.

More than 75% of patients have acquired mutations in one or more genes known to be recurrently altered in MDS.

Recurrent mutations in MDS implicate several molecular pathways in the development and progression of disease including; altered RNA splicing mechanisms, epigenetic changes in DNA methylation and histone modifications, activation of growth factor signalling cascades, impaired differentiation and abnormal regulation of cell cycle and apoptosis.

Acquired mutations in several MDS genes have prognostic significance that is independent of clinically based prognostic scoring systems.

Chromosomal abnormalities and mutations in some genes can predict response to specific therapies used to treat patients with MDS.
Genetics of Susceptibility to Mycobacterial Disease
Authors: Selvaraj Paramasivam , Alagarasu Kalichamy , Raghavan Sampathkumar
Published: April 2013

The genus Mycobacteria contains important pathogens of humans including

Mycobacterium tuberculosis

and

Mycobacterium leprae

. The outcome of mycobacterial infection is influenced by variations in human genes. Genetic susceptibility to mycobacteria involves multiple genes that contribute to the innate immune recognition of mycobacteria (genes coding for pattern recognition receptors), recognition of mycobacteria by the adaptive immune system involving products of human leucocyte antigen/major histocompatibility complex genes and effector responses of the immune system (genes affecting cytokines, chemokines and immunomodulators). Host genetic susceptibility to pathogens is complicated by the genetics of pathogen, gene‐environment and gene–gene interactions. Moreover, ethnicity specific effects further add fuel to the complication. A series of concerted comprehensive immunogenetic studies are warranted to decipher new molecular players and delineate complex host–pathogen interactions. This might identify the genetic factors that are definitely associated with mycobacterial diseases and could lead to development of novel therapeutics and prophylaxis. Convergence of immunogenomics, pharmacogenomics and vaccinomics could yield better tools to tackle these dreadful diseases of mankind.

Key Concepts:

Outcome of a mycobacterial infection depends on gender, age, HIV infection status, malnutrition, BCG vaccination, host immune responses, pathogen variation and host genetics, which varies according to ethnicity.

Extensive studies have implicated the role of alleles from human leucocyte antigen (HLA) genes/major histocompatibility complex (MHC) genes and single nucleotide polymorphisms (SNPs) of various non‐HLA genes/non‐MHC genes in conferring susceptibility to mycobacterial disease.

Polymorphisms in the genes coding for pattern recognition receptors such as toll‐like receptors, mannose‐binding lectins, mannose receptors, surfactant proteins and DC‐SIGN affect susceptibility to mycobacterial disease.

HLA‐DRB1
*
15 and HLA‐DQB1 alleles having aspartic acid at β57 have been shown to be associated with TB in many populations.

SNPs in the genes coding for
IFNG
,
IL10
,
CCL2
, vitamin D receptor,
NOS2A
and other effector molecules influence susceptibility to mycobacterial disease.

SNPs in the genes coding for immune mediators could predict response to treatment.

Ethnicity specific effects, and strain variation in the pathogen, gene–gene and gene–environment interactions affect genetic susceptibility.
Genetics of Chromosome 22q11.2 Deletion Syndrome
Authors: Fernández Luis
Published: April 2013

The 22q11.2 deletion syndrome is the most frequent deletion syndrome in humans. The genomic architecture of this chromosomal region makes it prone to anomalous meiotic rearrangements causing the loss of genetic material in the parental gamete. Gene dosage‐dependent embryonic developmental processes are subsequently disrupted and lead to multiple birth malformations, the severity of which is modulated by other unknown genetic and environmental factors. The resulting clinical picture is a heterogeneous phenotype with no correlation with the genetic lesion. Currently, genetic diagnosis is mostly performed by gene dosage quantification techniques targeting region 22q11.2, but the recent development of whole‐genome scanning methods enabling a full molecular characterisation of patients under uniform criteria and a better genotype–phenotype correlation will help to understand the pathogenesis of this disorder.

Key Concepts:

The 22q11.2 deletion syndrome is the most common human microdeletion syndrome.

It usually occurs
de novo
, although an estimated 10% of cases are inherited.

LCR22s are homologous DNA sequences that spontaneously mediate the deletion process during meiosis.

Parents should be studied both genomically and cytogenetically to rule out carrier status or occasional balanced rearrangements.

Phenotypic variability is likely to be due to genetic and environmental factors during development, and it hampers a genotype–phenotype correlation.

Genomic techniques will contribute to a better genotypic characterisation and understanding of the disease.
Technological Advances in the Detection of Novel Fusion Genes
Authors: Leow Pay Chin , Ku Chee‐Seng , Soo Ross , Soong Richie
Published: April 2013

Since their first discovery in chronic myeloid leukaemia, fusion genes have been shown to play a central role in haematologic cancers. However, aberrations arising from this type of somatic mutations have been neglected in common solid tumours, largely because of limitations of current cytogenetic techniques. The recent discovery of recurrent gene fusions in prostate and lung cancer has led to a renewed interest in the identification of novel fusion genes in solid tumours. In this review, we discuss the technical challenges of studying gene fusions in solid tumours, appraise the application of newer molecular techniques and highlight emerging technologies, with the focus on next‐generation sequencing and chromogenic
in situ
hybridisation, that have greatly enhanced the speed and reliability of gene fusion discovery in malignant solid tumours.

Key Concepts:

A fusion gene is a gene hybrid formed from linking two physically separated genes.

A fusion gene can occur as a result of chromosomal rearrangements such as translocations, insertions, deletions and inversions, which lead to novel protein fusion products.

The detection of fusion genes is being recognised as a promising clinical tool for the diagnosis, staging classification, prognosis and treatment of cancer.

Gene fusions have been an underappreciated class of mutation in solid tumours.

The identification of gene fusions in solid tumours is technically challenging due to the complex and often chaotic karyotypic profiles of solid cancers.

Recent advances in genomics obtained from next generation sequencing, coupled with the emerging field of bioinformatics and ever‐advancing molecular techniques, have uncovered many novel oncogenic fusion genes in solid tumours that were unable to be detected by traditional cytogenetic methods.

Fluorescence
In‐Situ
Hybridisation (FISH) is recognised as the most effective diagnostic methods for the detection of gene fusions.

Transcriptome‐sequencing (also known as RNA‐sequencing), a recently introduced high‐throughput method of characterising ribonucleic acid (RNA) transcribed from the genome is rapidly emerging as the key method for the discovery of gene fusions.

Numerous challenges and unanswered issues remained with the discovery of novel gene fusions and their development as effective targeted cancer therapies or as clinical diagnostic and/or prognostic tools.
Syphilis: Epidemiological Aspects
Authors: Wright David J , Norris Steven J , Dhillon Rishi H‐P , Edmondson Diane G
Published: April 2013

Syphilis continues to represent a significant public health issue. The number of cases globally remains high at over ten million newly infected patients each year, with highest rates seen in countries of low income. The main mode of transmission is by sexual contact, with men who have sex with men, co‐infection with human immunodeficiency virus (HIV) and the sexually promiscuous particularly at risk. Infection rates are also linked with times of war and social upheaval; this is also true of other sexually transmitted diseases.

Prevention of new cases is clearly desirable. Most major health organisations (including the CDC and WHO) have elimination plans which rely on education, promotion of safe sexual practices and screening of high‐risk individuals at the core of the strategy.

Key Concepts:

Clinical differences in the treponematoses have been attributed to adaptation of the organism to climatic factors.

An African rather than an American origin is suggested for syphilis.

The control of syphilis by public health measures is exemplified by a lower incidence of syphilis in Europe and North America than the rest of the world.

An increased incidence in syphilis is found associated with wars and civil disturbance.
History of Apoptosis Research
Authors: Jiang Lijing
Published: April 2013

Apoptosis‐like cell death was first observed in developing tissues using histological methods in the mid‐nineteenth century. Having been frequently rejected as experimental artefacts, such biologically active, well‐regulated cell death phenomena were reconfirmed in various research contexts during the first half of the twentieth century. In 1972, three pathologists observed cell death in pathological tissues and coined the term ‘apoptosis’ to distinguish the concept of physiological cell death from the concept of passive cell death, necrosis. In the 1980s and 1990s, modern molecular biotechnology transformed apoptosis research from a subject for mostly morphological investigation to a multivalent, interdisciplinary field important to developmental biology, biogerontology and cancer research.

Key Concepts:

Apoptosis is biologically active, well‐regulated physiological cell death mechanism that is involved in development, tumour suppression, tissue homoeostasis and degenerative diseases.

Apoptosis was discovered and defined initially through its unique morphology.

The discovery of apoptosis in development challenged assumptions in embryology in the early twentieth century.

Molecular methods transformed apoptosis research into an important biological and biomedical field.
Neurobiology of Overeating
Authors: Stice Eric , Burger Kyle S
Published: April 2013

The fact that some people are able to maintain a healthy weight, despite the omnipresence of high‐fat and high‐sugar foods, whereas others experience unhealthy weight gain, has prompted theories regarding individual difference factors that may increase risk for overeating. Some have proposed that individuals who experience less reward from food intake overeat to compensate for this reward deficit. Others have suggested that it is individuals who experience greater reward from food intake who are at risk for overeating. There is data from neuroimaging studies that investigate individual differences in response to food intake and food cues, as well as animal studies that support the reward deficit model, yet there is similar data to support the reward surfeit model. However, neither of these models fit with all of the data. We have therefore proposed a dynamic vulnerability model that appears to better account for the findings in the literature. This working model points to initial vulnerability factors as well as neural adaptations to overeating which may perpetuate overeating in a feed forward manner.

Key Concepts:

Advances in neuroimaging techniques allows for the direct assessment of how food reward can impact eating behaviour.

Multiple, conflicting theories of food reward and obesity have been presented.

Emerging animal and prospective human data suggest that reduced reward when consuming foods and hyper‐responsivity to food cues may evolve from overeating and perpetuate further overeating.

Initial hyper‐responsivity of brain regions that encode the reward value of food cues, coupled with greater responsivity of gustatory/oral somatosensory regions may be initial vulnerability factors of overeating.

Reduced inhibitory activation in response to food stimuli, and genotypes associated with compromised dopamine function may increase risk for overeating/weight gain.

Collectively, data point toward a dynamic vulnerability of overeating and obesity.
Pupillary Disorders
Authors: Walsh Ryan D , Liu Grant T
Published: April 2013

Pupillary abnormalities range from benign isolated findings to harbingers of significant, even life‐threatening, conditions. A complete understanding of the neuroanatomy underlying the innervations to the antagonistic pupillary sphincter and dilator muscles is essential to detecting, and discerning the importance of, a particular pupillary abnormality. The sphincter muscle receives neuronal input from the parasympathetic division of the autonomic nervous system, whereas the dilator muscle receives input from the sympathetic division. Afferent input carrying light information to the brain is transmitted by retinal ganglion cell axons via the optic nerves, chiasm, and tracts. The parasympathetic innervation to the pupil originates in the Edinger‐Westphal nucleus in the midbrain. The sympathetic innervation to the pupil consists of a three‐neuron pathway originating in the hypothalamus. Important pupillary disorders include physiologic anisocoria, relative afferent pupillary defect, amaurotic pupil, Argyll Robertson pupils, cranial nerve III palsy, pharmacologic mydriasis, tonic pupil, and Horner syndrome.

Key Concepts:

Examination of the pupil is an important part of the physician's neurological and ophthalmological evaluation of a patient.

The size of the pupil is controlled by the actions of antagonistic muscles located within the iris: the pupillary sphincter and dilator.

Constriction of the pupils is mediated by the parasympathetic nervous system, whereas dilation of the pupils is mediated by the sympathetic nervous system.

Pupillary constriction to light occurs via an involuntary reflex arc.

Retinal ganglion cell axons involved in carrying light information for the pupillary light reflex exit the optic tract (proximal to the lateral geniculate nucleus) to synapse in the midbrain pretectal nucleus.

The parasympathetic output controlling pupillary constriction originates in the Edinger‐Westphal nucleus in the midbrain and terminates at the pupil sphincter muscle.

Pupillary dilation involves a ‘three‐neuron’ sympathetic pathway, which originates in the posterolateral hypothalamus and terminates at the pupil dilator muscle.

A relative afferent pupillary defect is caused by a decreased amount of light information from the affected eye reaching the pretectal nuclei in the midbrain and is most commonly a sign of ipsilateral optic nerve pathology.

Damage to cranial nerve III can result in injury to the parasympathetic fibres travelling to the pupillary sphincter muscle, thus disrupting the efferent arc of the pupillary light reflex, resulting in deficient pupillary constriction on the involved side.

Horner syndrome, characterised by miosis, ptosis, and facial anhidrosis, results from disruption of the oculosympathetic pathway.
Genomic Novelty at the Vertebrate Ancestor
Authors: Kuraku Shigehiro
Published: April 2013

The group of vertebrates includes diverse evolutionary lineages, and typical laboratory‐model vertebrates are confined to only limited groups (tetrapods and teleost fishes) of its entire diversity. Accumulating information of the molecular sequence for the still‐missing lineages including jawless fishes can now provide deeper insights into the definition of the taxon Vertebrata at the genomic level. Above all, the so‐called two‐round whole genome duplications are described to have occurred in the early vertebrate evolution. Recent molecular phylogenetic analyses for some gene families resulted in a scenario in which the genome expansion might have been completed before the split of the lineage of cyclostomes (extant jawless fishes including hagfishes and lampreys) from the future jawed vertebrate lineage. In addition to this genome expansion, key features of genomic contents of the vertebrate ancestor are inferable, provided secondary changes introduced later in individual lineages are taken into deep consideration in ancestral phylogenetic reconstruction.

Key Concepts:

Large‐scale sequencing of genomes and transcriptomes of non‐model vertebrates in crucial phylogenetic positions provided valuable information about the vertebrates' entire diversity.

The two‐round genome duplications likely define the vertebrates genomically.

De novogenes should also have contributed to the vertebrate gene repertoire.

Lineage‐specific molecular changes should be taken into deep consideration in reconstructing the ancestral state as in morphological comparison.

Large‐scale sequence resources for early branching vertebrates are expected to provide clearer insights into the genomics' novelty which established the vertebrates.
Global Population and Global Justice: Equitable Distribution of Resources Among Countries
Authors: West‐Oram Peter GN , Widdows Heather
Published: April 2013

Analysing the demands of global justice for the distribution of resources is a complex task and requires consideration of a broad range of issues. Of particular relevance is the effect that different distributions will have on global population growth and individual welfare. Since changes in the consumption and distribution of resources can have major effects on the welfare of the global population, and the rate at which it increases, it is important to establish meaningful principles to ensure a just distribution of resources. In order to establish such principles we must consider the scope of any reproductive rights, and rights to other goods, such as food and health care, as well as examine the extent of duties correlating to those rights. In addition to the impact that distributions of global goods have on the welfare of current generations, it is also important to consider what duties we have, if any, to future generations.

Key Concepts:

Questions relating to global justice are concerned with the justice of international institutions and events; they are also concerned with establishing fundamental moral principles, which form the basis of international law.

Human rights are those rights which are held by all people in virtue of their status as human beings, rather than because of any specific law or in virtue of belonging to a specific group or country.

The distribution and consumption of resources is important in discussion of global justice since the way in which resources are allocated will have a major effect on human welfare and ability of individuals to enjoy their rights.

Distributive Justice can be analysed on a range of scales, from the local to the global and deals with questions relating to the distribution of resources and other important goods; these can be things like money, health care, or food, as well as more intangible concepts like freedom and liberty.

Environmental sustainability is important in the global justice context because environmental degradation can have severe impacts on human welfare; as such, the sustainability of different types, and rates, of resource consumption will be more or less just, depending on the harm that is caused by it.

Egalitarianism is the view, common in discussions of justice that all human beings are morally equal and that as a result, should be given equal moral consideration.

Prioritarianism is the view in theories of justice that a specific group, for example the citizens of a particular country, or those living in poverty should have their needs prioritised over the needs of other groups.

Sufficientarianism is the view that justice requires only that everyone has enough and that all people have sufficient resources or are above a specific welfare threshold, contrary to egalitarianism, sufficientarianism is compatible with the existence of unequal distribution of goods.
Philosophy of Neuroscience
Authors: Bickle John , Hardcastle Valerie Gray
Published: April 2013

Since its inception more than a quarter‐century ago, the philosophy of neuroscience has grown into a recognised field in the philosophy of the special sciences. It focusses on foundational issues in the discipline, but also anticipates developments in the neurosciences that bear on epistemological, ethical and cultural concerns. In this paper, life scientists are introduced to three current issues in the philosophy of neuroscience: a new version of the old reductionism‐versus‐integrationism debate, spurred recently by ‘new mechanist’ philosophers of neuroscience; a challenge to ‘dynamicist’ explanations in neuroscience, as either covertly mechanistic or nonexplanatory; and a brief introduction to the burgeoning field of neuroethics and neurolaw, which is finding new discoveries in neuroscience that bear on both familiar ethical debates and generate novel ethical and legal concerns.

Key Concepts:

Philosophy of neuroscience is now a recognised field in the philosophy of the special sciences (biology, psychology and economics).

The reductionism‐versus‐integrationism debate has reemerged in an interesting new form due to the recent work by ‘new mechanist’ philosophers of neuroscience.

The debate among mechanist‐integrationists, mechanistic reductionist and ruthless reductionists turns on the viability and extent of nested hierarchies of mechanisms in neuroscience.

Some ‘new mechanists’ have challenged dynamicist explanations in neuroscience, suggesting that such explanations are not distinct from causal‐mechanistic explanations, and even questioning whether such ‘explanations’ are genuine at all.

Neuroethics includes both the study of ethical issues raised or influenced by neuroscientific discoveries, and the neuroscience of ethical judgment and decision‐making.

Brain interventionist technologies and neuropharmacology raise difficult questions about the ethical dimensions of potential cognitive enhancement.

Existing and foreseeable brain interventions encroach upon deep philosophical questions about personal identity and basic fairness.

The increasing use of neuronal evidence in law courts raise troubling issues about brain‐realism and the potential impact such evidence may have on juries and judges.
Obesity Hormones in Health and Disease
Authors: Caylak Emrah
Published: April 2013

Obesity is a medical condition as excess body weight in the form of fat, resulting from a chronic imbalance of energy homoeostasis. The prevalence of obesity in adults and children is rapidly rising and it is now the major contributors to metabolic disorders. Energy balance is controlled with short‐ and long‐term signals generated by the central nervous system, gastrointestinal tract and adipose tissue. The knowledge of obesity hormones (adipokines) released by adipose tissue will allow us to develop new anti‐obesity pharmacotherapies amplifying anorexigenic and lipolytic signalling or blocking orexigenic and lipogenic signalling.

Key Concepts:

Obesity is a medical condition resulting from the failure of energy homoeostasis. Obesity is most prevalent in westernised countries, associated with some chronic diseases (i.e. type 2 diabetes, cardiovascular diseases and cancers), shortens life duration and the increases mortality rates.

There has been important endocrine alterations in many physiological systems are attracting interest to understand the pathological mechanisms of obesity.

Although adipose tissue can be considered as storage organ of excess energy, adipocytes released adipokines to control the growth of adipose tissue or the energy homoeostasis and body weight regulation.

Obesity hormones (adipokines) released by adipose tissue to play a major role in the regulation of energy homoeostasis such as adiponectin, apelin, angiotensin II, ASP, leptin, PAI‐1, MCP‐1, omentin, resistin, visfatin, proinflammmatory cytokines and glucocorticoids.

Understanding the physiological and pathological roles of adipokines in health and disease in humans will allow us to find potential therapeutic targets for the treatment of obesity‐related disorders.