bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics of Williams–Beuren Syndrome
Authors: Merla Giuseppe , Micale Lucia , Fusco Carmela , Loviglio Maria Nicla 
Published: April 2013

Abstract

The Williams–Beuren syndrome is a rare genomic disorder caused by a hemizygous microdeletion of approximately 30 genes at 7q11.23 occurring by nonallelic homologous recombination between low copy repeats flanking that region. The 7q11.23 region has been also found duplicated, triplicated and inverted in patients with different and, in some instances, reciprocal phenotypes.

Complementary strategies including mouse models, functional and biochemical studies have been pursued in the recent years to delineate the individual and/or combined contribution of hemizygous genes to the wide spectrum of phenotypes that characterises this syndrome. Haploinsufficiency of several of these genes has been reported to account for parts of the overall phenotypes, suggesting their sensitivity to gene dosage. Notably,
MLXIPL
,
GTF2IRD1
and
GTF2I
hemizygous genes act as transcription factors, therefore is likely that their haploinsufficiency is responsible for some of clinical features by regulating gene expression of a wide number of target genes.

Key Concepts:

Williams–Beuren syndrome is a genomic disorder characterised by a unique cognitive profile and it involves approximately 30 hemizygous genes at 7q11.23.

The 7q11.23 Williams–Beuren syndrome region has been found deleted, duplicated, triplicated and inverted in patients with different phenotypes.

Patients with atypical deletions and mouse models have provided insights about the genotype–phenotype correlations.

Haploinsufficiency of the Williams–Beuren syndrome genes is correlated with the clinical signs.

BAZ1B
has been linked to cardiac, craniofacial and hypercalcemia defects; hemizygosity of
MLXIPL
could be related to the diabetic phenotype of Williams–Beuren syndrome patients through regulation of glucose metabolism.

The GTF2IRD1 transcription factor modulates genes involved in tissue development and differentiation and is a strong candidate for the craniofacial and neurobehavioral features.
Molecular Genetics of Malignant Mesothelioma
Authors: Sekido Yoshitaka 
Published: April 2013

AbstractMalignant mesothelioma (MM) is an aggressive tumour arising primarily from the pleural or peritoneal cavities. MM develops by asbestos exposure after a long latency, which is highly refractory to conventional therapeutic modalities. Molecular genetic analysis has revealed several key genetic alterations which are responsible for the development and progression of MM. The frequently mutated tumour suppressor genes detected in MM cells areCDKN2A/ ARF,NF2,BAP1, andLATS2. In contrast, frequent activating mutation of any oncogenes has not been clearly identified yet, which is one of the reasons that current molecular target therapy is not very effective for MM patients. Recent studies have also indicated characteristic epigenetic alterations in MM, which include distinctdeoxyribonucleic acid (DNA)methylation patterns and the involvement of noncodingribonucleic acid (RNA). Aberrant histone modification caused byBAP1inactivation may also lead to the disturbance of global expression profiling. With further comprehensive genome analyses, new genetic and epigenetic alterations in MM cells are expected to be revealed more precisely, and the new knowledge based on them would be applied for developing a new diagnostic tool and new target therapies against MMs.Key Concepts:Malignant mesothelioma cells harbour multiple key genetic mutations, which mainly inactivate tumour suppressor genes.Asbestos fibre induces chromosome and DNA damages in normal mesothelial cells with several possible mechanisms, but it is not clear why it takes so long from asbestos exposure to mesothelioma development.People differ in their susceptibility to development of mesothelioma after similar levels of asbestos exposure, possibly due to the differences in genetic polymorphisms or expression levels of genes involved in the DNA repair system and epigenetics modification.Mesothelioma has long been considered a representative type of tumour primarily caused by environmental factors, especially asbestos, but familial cases of mesothelioma with a specific gene mutation have challenged this idea.Neurofibromatosis type 2 (NF2) gene inactivation is found in a nearly half of mesothelioma cases and the inactivation of one of its downstream signal transduction cascades, Hippo signalling, plays a significant role in dysregulation of cell proliferation.Epigenetic alterations such as aberrant histone modification by BAP1 gene inactivation play significant roles in mesothelioma development.The overall picture of the genetic abnormality landscape of mesothelioma cells lags behind other common human malignancies.If an oncogene‐type gene with frequent activating mutation in mesothelioma cells were discovered, molecular target strategies aiming at controlling the activated molecule could be aggressively pursued to develop new therapeutic tools against mesothelioma.
Molecular Genetics and Immunopathogenesis of Psoriasis
Authors: Lepre Tiziana , Zampatti Stefania , Novelli Giuseppe , Giardina Emiliano 
Published: April 2013

AbstractPsoriasis (OMIM #177900) is a common chronic disease of the skin that affects approximately 2–3% of the population. Typical lesions of psoriasis are characterised by red and scaly skin patches, usually found on the scalp, elbows and knees and often associated with severe arthritis. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. The onset of the disease is generally between 10 and 40 years of age. Type 1 begins at or before the age of 40 years; type II begins after the age of 40 years. Psoriasis is a complex disease due to the interaction between environmental factors and susceptibility alleles. Life style, diet, smoking, stress and infections are the best validated environmental factors predisposing to the pathology. During the past several years, researchers have identified different loci related to the disease, namely fromPSORS1toPSORS13.Key Concepts:Multifactorial diseases are common disease due to the interaction between environmental factors and different susceptibility loci.Psoriasis, a chronic disease of the skin, is a common disease affecting approximately 2–3% of the population.Psoriasis is a complex disease. Different loci are known to be responsible for its development, together with some environmental factors, such us life style, diet, smoking, stress and infections.Immune system is responsible for the development of psoriasis: HLACw*06:02 is the best replicated and validated susceptibility allele.Understanding the genetic and epigenetic basis of psoriasis will help to further outline the molecular mechanism of onset and progression.
Capillary Malformation–Arteriovenous Malformation andRASA1Mutations
Authors: Boon Laurence M , Revencu Nicole , Vikkula Miikka 
Published: April 2013

AbstractCapillary malformation–arteriovenous malformation (CM–AVM) is a subtype of CM that is inherited as an autosomal‐dominant disorder. Patients typically have multiple small pinkish‐reddish CMs, often with a halo. These lesions are randomly distributed on the body. About 15–20% of patients have an associated arteriovenous fistula or malformation often located on head and neck. The fast‐flow lesions involve skin, subcutaneous tissue, muscle and/or bone or the brain or the spine. Parkes Weber syndrome and vein of Galen aneurysmal malformation are also part of CM–AVM. Most CM–AVM patients have a detectableRASA1mutation causing loss‐of‐function of p120RASGAP, a guanosine triphosphatase‐activating protein, which participates in the regulation of the Ras signalling pathway. Most mutations are private and no genotype–phenotype correlation has been identified. A somatic second hit is likely necessary to produce lesional, complete loss‐of‐function of p120RASGAP, as the malformations are localised, and often multifocal. Ras‐pathway modulators may provide futuristic therapies for CM–AVM.Key Concepts:Multifocal, often small, capillary malformations may be hereditary.Lesions with pale reddish‐brownish colour, a halo and/or a good demarcation line suggest CM–AVM.Numerous miliary telangiectasias (often on extremities) are also suggestive of CM–AVM.Many, but not all patients, also have a fast‐flow lesion.Distribution of fast‐flow lesions differs from that of hereditary haemorrhagic telangiectasia.Until better statistics exist, clinical examination should include T1/T2 brain MRI, when molecular diagnosis is confirmed.These CMs do not respond well to current lasers.RASA1‐dominant mutations are mostly private, that is, specific to each family.Parkes Weber syndrome patients with CMs elsewhere on the body are likely to carry aRASA1mutation.Family history is not necessarily present, asde novomutations occur.
Molecular Genetics of Migraine
Authors: Stuart Shani , Maher Bridget H , Oikari Lotta , Griffiths Lyn R 
Published: April 2013

Abstract

Migraine is a common neurological disorder with a significantly heritable component. It is a complex disease and despite numerous molecular genetic studies, the exact pathogenesis causing the neurological disturbance remains poorly understood. Although several known molecular mechanisms have been associated with an increased risk for developing migraine, there remains significant scope for future studies. The majority of studies have investigated the most plausible candidate genes involved in common migraine pathogenesis utilising criteria that takes into account a combination of physiological functionality in conjunction with regions of genomic association. Thus, far genes involved in neurological, vascular or hormonal pathways have been identified and investigated on this basis. Genome‐wide association studies (GWAS) studies have helped to identify novel regions that may be associated with migraine and have aided in providing the basis for further molecular investigations. However, further studies utilising sequencing technologies are required to characterise the genetic basis for migraine.

Key Concepts:

Migraine can present with variable phenotypes, which may confound results from gene association studies where some traits are more prevalent than others contributing to variability between populations.

Migraine is a genetically heterogeneous disorder and this may contribute to the difficulty in replicating gene associations in different populations.

Pedigree‐based studies may assist to reduce genetic and phenotypic heterogeneity to identify molecular mechanisms or pathways involved in pathogenesis that may then be investigated at a population level.

Current migraine genetic studies focus on genes involved in hormonal, vascular or neurological pathways.

GWAS have provided some success in identifying novel genomic regions for investigation.

Investigation of the mitochondrial genome is an emerging area of investigation in migraine research.

Sequencing will assist to identify novel rare or family‐specific variants that may implicate genes for further research.
Nuclear Envelope Assembly and Disassembly During the Cell Cycle
Authors: Chen Rey‐Huei 
Published: April 2013

AbstractThe nuclear envelope of metazoa breaks down at the onset of mitosis and reassembles at the end of mitosis. This process is mainly controlled by the cyclin‐dependent kinase that phosphorylates inner nuclear membrane (INM) proteins to disrupt their association with chromatin and to disintegrate the nuclear lamina. Upon nuclear envelope breakdown, the nuclear membrane and integral nuclear membrane proteins retract into the endoplasmic reticulum (ER), whereas other peripheral nuclear membrane proteins and some components of the nuclear pore complex become disperse in the cytosol. At late anaphase, inactivation of the cyclin‐dependent kinase and dephosphorylation of INM proteins allow these proteins to bind the chromatin and brings the ER membrane to the chromatin surface to initiate nuclear envelope assembly around the compact chromosome mass. The nuclear envelope disassembly and assembly are thus coordinated with the segregation of sister chromatids in each cell division cycle to maintain genome stability.Key Concepts:The nuclear envelope is a dynamic structure that is continuous with the ER.The INM proteins associate with and organise the chromatin.The disassembly of nuclear envelope is triggered by the cyclin‐dependent kinase at the onset of mitosis.Phosphorylation of INM proteins disrupts their interaction with chromatin.Nuclear envelope breakdown is essential for sister chromatid segregation.Integral nuclear membrane proteins diffuse into the ER after nuclear envelope breakdown.The nuclear envelope reassembles around compact chromosome mass at late anaphase/telophase.Nuclear envelope reassembly is mediated by multiple interactions of the INM proteins with chromatin.Dephosphorylation of INM proteins at late anaphase/telophase is required for nuclear envelope reassembly.
Cellular Basis of Laminopathies
Authors: Cao Kan 
Published: April 2013

Abstract

The nuclear lamina is the main architectural component of a eukaryotic nucleus. More than an inert scaffold, the lamina is essential for maintaining proper nuclear organisation, epigenetic composition, transcriptional regulation and cell cycle progression. Mutations within lamin genes lead to a wide range of diseases known as laminopathies, among which the striking premature aging disease Hutchinson–Gilford progeria syndrome (HGPS) is the most well known. Studies regarding the cellular basis of laminopathies have advanced our knowledge of the nuclear lamina and yielded remarkable insights into the process of normal human aging. Understanding the molecular mechanisms responsible for disease manifestations has also led to the development of novel therapeutic strategies to address lamina‐related diseases. Ultimately, scientists and clinicians seek to provide treatment options to laminopathy patients to alleviate symptoms and perhaps to cure these diseases in the future.

Key Concepts:

Mutations in genes encoding lamin proteins lead to a wide range of diseases known as laminopathies.

The nuclear lamina plays essential roles in maintaining nuclear architecture, chromatin organisation, cellular differentiation and gene expression.

Studies of the molecular mechanisms underlying laminopathies have led to advances in the understanding of lamin structure and function.

Progerin, the mutant form of lamin A expressed in Hutchinson–Gilford progeria syndrome, is also present in normal individuals, albeit at a low level.

Recent advances have led to the development of noval therapeutic options for patients suffering from HGPS.
Cytokinesis
Authors: Gregory Stephen L , Saint Robert 
Published: April 2013

Abstract

Cytokinesis is the term given to the division of a cell into two daughter cells. Cytokinesis in all cells requires the resolution of the single lipid bilayer of the parent cell into separate bilayers enclosing the two daughter cells, yet cytokinesis mechanisms differ markedly in different cell types. In bacteria, a ring of FtsZ protein filaments constricts the membrane. FtsZ‐like proteins operate in some Archeal species, but others use a different mechanism. In plants, vesicles are deposited by microtubules in the centre of the cell to create sheets of membrane that grow outwards until they reach and fuse with the cytoplasmic membrane. In animal cells, actin and myosin form a contractile ring, which draws the membrane inwards. Bundled microtubules and vesicle trafficking then complete the separation (abscission). In all cases, cytokinesis closely follows chromosome segregation and constriction occurs between the separating chromosomes to ensure the genetic integrity of the daughter cells.

Key Concepts:

To make two cells from one, the DNA needs to be copied, the two copies separated and the cell divided (cytokinesis) so that one DNA copy resides in each daughter cell.

The cytoplasmic membrane of the parent cell must resolve into the two cytoplasmic membranes of the daughter cells.

Cell division frequently involves the formation of a ring of protein filaments that attaches to the membrane and constricts, drawing the membrane inwards.

In many bacterial cells, the main component of this ring is the FtsZ protein. In animal cells, the main components are actin and myosin.

In plant cells, microtubules form across the future site of division and deposit membrane vesicles which fuse to form the new membrane.

In many eukaryote cells, the mitotic spindle allows the DNA to separate, and then signals the cell to determine the plane of division.

In animals, the final separation of daughter cells involves vesicles fusing with the cell membrane.

Errors in cytokinesis have serious implications for cancer.
Neurogenesis in the Developing Mammalian Neocortex
Authors: Kelava Iva , Huttner Wieland B 
Published: April 2013

AbstractThe neocortex is the evolutionarily newest and most complex part of the mammalian brain. The neurons of the neocortex are born from different neural stem and progenitor cells (for simplicity collectively referred to as progenitors) that reside in proliferative zones during embryonic development. During the neurogenic period, distinct populations of neural progenitors appear, each having specific molecular and cell biological characteristics. These characteristics and the environment of the neural progenitor are responsible for the self‐renewing or neurogenic potential of each neural progenitor type. The fate of daughter cells after neural progenitor division is determined by the mode of division, intrinsic factors such as transcription factors or regulatoryribonucleic acids(RNAs), and by extrinsic signals coming from the surrounding cells. This tight regulation controls the rate of production of neural progenitor types and neurons. The ratios of different progenitor types have a huge impact on the final number of neurons in the adult neocortex, and are partly responsible for vast differences in the brains of different mammals.Key Concepts:Neocortex is a part of the brain characteristic of mammals.Neocortex is a six‐layered structure comprised of post‐mitotic neurons and glial cells.Neocortical neurons are born from neural progenitor cells, mostly during embryonic development.Neural progenitor cells can be classified into different populations based on molecular and cell‐biological features.The molecular and cell‐biological features of neural progenitor cells influence their propensity to self‐renew or produce neurons.Neural progenitor cells are under tight intrinsic and extrinsic control, in order to maintain the equilibrium between proliferative and neurogenic divisions.The relative abundance of different progenitor populations influences the final number of neurons in the adult neocortex.
Animal Mating Systems
Authors: Klug Hope 
Published: April 2013

Abstract

The term mating system refers to the way in which individuals are grouped in relation to mating, and/or characteristics of mate acquisition and mating behaviour. Animal mating systems are incredibly diverse and have been most generally classified as monogamous (a single male and single female mate exclusively with one another) or polygamous (males and/or females mate with multiple individuals). There are three classic polygamous mating systems: polygyny (a male mates with more than one female), polyandry (a female mates with more than one male) and polygynandry (both males and females have more than one mate). Some researchers have developed more specific mating system classifications, and this remains an area of active research. Mating systems are influenced by many factors, including the spatial and temporal distribution of sexually receptive males and females, resource availability and distribution, male and female life history, sexual selection and parental care.

Key Concepts:

Mating system refers to the way in which individuals are grouped in relation to mating and/or details of mating dynamics.

Animal mating systems are highly variable within and between taxonomic groups.

Mating systems are dynamic and change through time.

Common mating systems include monogamy, polygyny, polygamy and polygynandry.

More specific descriptors of mating systems have been developed that account for pair bond duration, resource use and defence and behaviour such as parental care.

Animal mating systems are affected by the spatial and temporal distribution of receptive mates, resource use and defence, male and female life history, sexual selection and parental care.
Evolution of Viviparity in Salamanders (Amphibia, Caudata)
Authors: Buckley David 
Published: April 2013

Abstract

Reproductive modes in salamanders (Amphibia, Caudata) are highly diverse. Viviparity, for instance, implies the retention of the developing embryos inside the females until the end of the gestation, at which point they deliver fully developed terrestrial juveniles. From an ecological point of view, the evolution of viviparity is highly significant, since it implies the semi‐independence of water for an amphibian. Nevertheless, viviparity is not very common among salamander. It has independently evolved only in a few species, all included within the family Salamandridae. Furthermore, the characteristics of viviparous strategies are different among species, although they all share some commonalities. The detailed study of these particular and common features in a phylogenetic context will reveal the genetic, physiological, developmental, morphological and historic factors that have triggered the evolution of this peculiar mode of reproduction in only one lineage among all the species of salamanders.

Key Concepts:

Viviparity entails the complete development of the progeny within the mother's genital tract, together with the maternal provisioning of nutrients to the embryos.

Since development occurs within the females, viviparity in amphibians implies that the aquatic phase of the standard amphibian life cycle is obviated in viviparous species.

Viviparity has independently evolved only in a few species of salamanders.