bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of Carney Complex
Authors: Horvath Anelia , Stratakis Constantine A 
Published: April 2013

Abstract

Carney complex (CNC) is an autosomal dominant multiple neoplasia and lentiginosis syndrome characterised by spotty skin lesions, cardiac and other myxomas and different types of endocrine tumours. The
PRKAR1A
gene, which codes for the regulatory subunit type 1‐alpha of the cyclic
adenosine monophosphate
(cAMP)‐activated protein kinase A, is responsible for more than two‐thirds of the cases of CNC described to date. Currently, more than 120 different disease‐causing
PRKAR1A
sequence variants have been reported. Other involved genes for adrenal hyperplasias include phosphodiesterases
PDE11A
and
PDE8B
. Additional genes are likely to be identified that may expand our understanding on the pathophysiology of the cAMP signalling pathway and how genetic defects cause CNC and its individual components such as adrenal tumours.

Key Concepts:

Inactivating
PRKAR1A
mutations cause CNC because
PRKAR1A
haploinsufficiency leads to uncontrolled PKA activity.

The majority (∼80%) of
PRKAR1A
mutations causing CNC result in an early stop codon generation and degradation of the mutant RNA through nonsense‐mediated RNA decay (NMD).

Recently, novel types of
PRKAR1A
mutations have been described: large gene rearrangements and small indels resulting in an elongated protein through downstream shift of the stop codon.

The penetrance of
PRKAR1A
mutations is more than 95% by the age of 50 years.

PDE11A
and
PDE8B
genetic defects contribute to the CNC phenotype, but they may also independently cause forms of adrenal hyperplasia, mainly isolated micronodular adrenocortical disease (iMAD).

Genotype–phenotype correlation is limited, but there are certain mutations that cause more frequently certain endocrine manifestations such as isolated Cushing syndrome.

The use of new genomic techniques has led to the identification of new genetic defects in
PRKAR1A
and related genes in CNC.
Molecular Genetics of Choroideremia
Authors: Freund Paul R , MacDonald Ian M 
Published: April 2013

AbstractChoroideremia (CHM) is an X‐linked disorder that causes progressive loss of vision. Affected males initially present with nyctalopia (night blindness) and experience progressive loss of peripheral vision until they are legally blind by middle age. Degeneration continues until there is a complete loss of vision. CHM is caused by mutations in theCHMgene, which encodes Rab escort protein (REP) 1. Molecular genetic techniques have identified more than 100 mutations affecting in theCHMgene and all but one results in the absence of REP1 protein. The degenerative process of CHM initially affects rod photoreceptors and the retinal pigment epithelium (RPE), then progresses to involve the choroid and cone photoreceptors. The exact pathophysiological mechanism of this degradation has not yet been elucidated. There is no established treatment for CHM available at this time but gene therapy trials are currently underway.Key Concepts:Choroideremia is a progressive degenerative disorder affecting the photoreceptor, retinal pigment epithelium and choroid layers of the retina.Mutations in theCHMgene result in the absence of REP1 protein, causing low levels of prenylation of RAB proteins.Confirmatory testing for CHM can be done by direct sequencing of theCHMexons or through immunoblot analysis for CHM protein expression.Zebrafish and mouseCHMknock‐out models have significant limitations due to the lack of viability. A conditional knock‐out mouse model has been developed and used in pre‐clinical testing of CHM therapies.Successful techniques in gene therapy for Leber congenital amaurosis‐2, another single gene disorder of blindness, are currently being applied to choroideremia.
Molecular Genetics of Galactosaemia
Authors: Lai Kent , Marabotti Anna , Mao Rong 
Published: April 2013

Abstract

The three different enzymes of galactose metabolism (galactokinase, galactose‐1‐phosphate uridyltransferase, UDP‐galactose‐4‐epimerase) can be impaired by genetic alterations, leading to three different forms of the genetic disease, galactosaemia. Their clinical outcome can vary from very mild to lethal depending on the enzyme involved, and on the respective gene mutations, but a clear‐cut correlation between genotype and phenotype of patients is not yet known. Understanding the molecular genetics of galactosaemia is essential to correlate the genotype of the patients to their phenotype, and eventually to their clinical outcome. The prediction of the effects of genetic alterations on enzyme structure and functions is just the first step of the long journey towards the final scope: to render clinicians and scientific community the tools to predict the effect of a galactosaemia‐linked mutation on the future quality of life of an affected newborn, in order to provide the best personalised solutions for the treatment.

Key Concepts:

Disorders in galactose metabolism in humans caused by hereditary deficiencies of the enzymes in the Leloir pathway can lead to severe and potentially lethal diseases called galactosaemia.

Depending on the specific enzyme that is deficient, three types of galactosaemia (Type I, II and III) with varying severity can occur.

Newborn screening programmes for galactosaemia are implemented in many developed countries to prevent acute lethality in the affected neonates.

The genes encoding the enzymes associated with all types of galactosaemia have been isolated, allowing the determination of the deleterious changes leading to the diseases.

Many of the variations seen in the
GAL
genes are private in nature, although specific changes are prevalent in different ethnic populations.
Molecular Genetics of Hermansky–Pudlak Syndrome
Authors: Cullinane Andrew R , Huizing Marjan , Gahl William A 
Published: April 2013

Abstract

Hermansky–Pudlak syndrome (HPS) is an autosomal recessive, genetically heterogeneous disorder characterised by oculocutaneous albinism and a bleeding diathesis. Subtype specific features such as neutropenic immunodeficiency and fatal lung fibrosis also occur. To date, nine human HPS subtypes (HPS‐1 to HPS‐9) and their associated genes have been identified. All of the HPS protein products are involved in biogenesis of lysosome‐related organelles (LROs) in specialised cells, including melanosomes in melanocytes and delta granules in platelets. The HPS proteins are all components of one of three biogenesis of lysosome‐related organelles complexes (BLOC‐1, BLOC‐2 or BLOC‐3) or the adaptor protein complex‐3. These complexes are essential for the correct formation of LROs, which are produced by the complex interaction of proteins, membranes and vesicles from the endocytic and biosynthetic pathways. Cells from patients with LRO disorders serve as useful tools for elucidating the complex pathways involved in the biogenesis of these organelles.

Key Concepts:

HPS is caused by mutations in nine known genes and is characterised by oculocutaneous albinism and a bleeding tendency.

The proteins that are encoded by the HPS genes are all required for the correct formation of lysosome‐related organelles (LROs).

LROs share features with lysosomes but have distinct morphology, composition and/or functions.

LROs are maintained by the regulated flow of proteins, membranes and vesicles among the complex endosomal machinery.

Novel players of LRO biogenesis are revealed by human disease and animal mutations, which continue to provide invaluable resources for elucidating the complex pathways involved in the biogenesis of these organelles.
Molecular Genetics of Nemaline Myopathy
Authors: Sandaradura Sarah A , North Kathryn N 
Published: April 2013

Abstract

Nemaline myopathy (NM) is a rare neuromuscular condition characterised by muscle weakness, hypotonia, depressed or absent deep tendon reflexes and nemaline bodies (rods) on skeletal muscle biopsy. There are six clinical subtypes, ranging from a severe congenital form to a milder phenotype with onset in childhood or adulthood. Pathogenic mutations have been described to date in 8 genes, the majority of which encode protein components of the muscle thin filam
ent
, and there is evidence of further genetic heterogeneity. Genotype–phenotype correlation is limited. Inheritance may be autosomal dominant or autosomal recessive and

de novo

dominant mutations are common. The most common genetic causes are autosomal recessive mutations in
NEB
and

de novo

autosomal dominant mutations in
ACTA1.
There is significant overlap between subtypes and variability in severity of manifestations. Animal models have assisted understanding of pathogenesis.

Key Concepts:

NM is one of the most common forms of congenital myopathy.

Typical clinical features include weakness, hypotonia and depressed or absent deep tendon reflexes.

Inheritance may be autosomal recessive, autosomal dominant or sporadic (new dominant).

Mutations in 8 genes have been associated with NM, and there is evidence of further genetic heterogeneity.

Autosomal dominant mutations in
ACTA1
and autosomal recessive mutations in
NEB
are the most common known genetic causes.

Current understanding of genotype–phenotype correlation is limited.

Molecular genetic testing and prenatal diagnosis are available clinically.

Clinical and histological features assist prioritisation of molecular genetic testing.

New technology, such as exome sequencing, will aid gene discovery and molecular diagnosis in NM.
Molecular Genetics of Simpson‐Golabi‐Behmel Syndrome Type 1
Authors: Golabi Mahin , Leung Alva 
Published: April 2013

AbstractSimpson‐Golabi‐Behmel syndrome (SGBS; OMIM #312870) is a recessive X‐linked overgrowth disorder manifesting multiple congenital anomalies and visceral and skeletal abnormalities. It is caused by deletions or duplications of the heparan sulfate proteoglycan glypican 3‐gene (GPC3; OMIM #30037) and/or duplication of the glypican 4‐gene (GPC4; OMIM #300168) at Xq26. Heparan sulfate proteoglycans mechanism of GPC3 and GPC4 in producing the SGBS phenotype is poorly understood and SGBS is suspected to be under‐reported. Suspected SGBS individuals should be tested for GPC3 mutations or deletion and GPC4 duplication. Current literature states no correlation between deletion size and phenotype for SGBS. Future investigative studies are recommended to define genotype–phenotype correlation and understand the GPC3/GPC4 gene‐product mechanism.Key Concepts:GPC3 and GPC4 lay tandem in sequence within the Xq26 locus.The glypican‐3 protein mediates embryonic and cell‐specific tissue formation and development by regulating growth factors.Point mutations or microdeletions in GPC3 or duplication of GPC4 result in a premature termination codon and will be translated to a truncated protein or nonfunctional glypican‐3 or glypican‐4 protein.Loss‐of‐function mutation in GPC3 is associated with SGBS but further studies on GPC4 are necessary to define its association with SGBS.Current literature states no correlation between deletion size and phenotype for SGBS.
Sudden Infant Death Syndrome: The Role of Cardiac Ion Channel Mutations
Authors: Wilders Ronald 
Published: April 2013

Abstract

The sudden infant death syndrome (SIDS) causes the sudden and unexplained death of an apparently healthy infant. Primary electrical diseases of the heart, with lethal arrhythmogenic events as a result of dysfunctioning cardiac ion channels (‘ion channelopathies’), may underlie such death. Genetic analysis in cohorts of SIDS victims (‘molecular autopsy’) has revealed a large number of mutations in ion channel‐related genes linked to inheritable arrhythmogenic syndromes, in particular the long QT syndrome, the short QT syndrome, the Brugada syndrome and cathecholaminergic polymorphic ventricular tachycardia. Combining data from population‐based cohort studies, it can be concluded that one out of five SIDS victims carries a mutation in a cardiac ion channel‐related gene and that the majority of these mutations are of a known malignant phenotype.

Key Concepts:

The sudden infant death syndrome (SIDS) is defined as “the sudden unexpected death of an infant <1 year of age, with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including performance of a complete autopsy and review of the circumstances of death and the clinical history”.

The pathophysiology of SIDS is still poorly understood, and SIDS remains a diagnosis of exclusion.

SIDS is a multifactorial disorder, with multiple factors contributing or predisposing to its development.

Long QT syndrome, short QT syndrome, Brugada syndrome and cathecholaminergic polymorphic ventricular tachycardia are inheritable cardiac disorders, with arrhythmogenic and possibly lethal events as a result of mutations in cardiac ion channel‐related genes.

As primary electrical diseases these ion channelopathies are not detectable during a standard post‐mortem examination.

The role of cardiac ion channel mutations as contributors to SIDS is currently well established.

At least one out of five SIDS victims carries a mutation in a cardiac ion channel‐related gene and the majority of these mutations are of a known malignant phenotype.
Structure, Function and Evolution of The Nematode Genome
Authors: Rödelsperger Christian , Streit Adrian , Sommer Ralf J 
Published: April 2013

AbstractIn the past few years, an increasing number of draft genome sequences of multiple free‐living and parasitic nematodes have been published. Although nematode genomes vary in size within an order of magnitude, compared with mammalian genomes, they are all very small. Nevertheless, nematodes possess only marginally fewer genes than mammals do. Nematode genomes are very compact and therefore form a highly attractive system for comparative studies of genome structure and evolution. Strikingly, approximately one‐third of the genes in every sequenced nematode genome has no recognisable homologues outside their genus. One observes high rates of gene losses and gains, among them numerous examples of gene acquisition by horizontal gene transfer. Not only does the ‘gene for parasitism’ not exist, but also there appear to be no common genomic characteristics of parasitic nematode genomes which would distinguish them from genomes of free‐living nematodes.Key Concepts:Nematode genomes tend to be compact.Nematode genomes vary in their gene composition due to extensive gene gain and loss.Genes are lost through gene deletion or rapid evolutionary change beyond the point where they can be recognised as homologous to a gene in another species.Genes are acquired through gene duplication,de novoformation and horizontal gene transfer.Horizontal gene transfer allows nematode species to acquire new physiological properties.All nematode genomes sequenced so far contain operons, multigene transcription units giving rise to a single pre‐mRNA, which is broken up into single protein coding mRNAs by trans‐splicing and polyadenylation.Within the nematodes parasitism has arisen multiple times independently and a ‘gene for parasitism’ or unifying parasite genomic features were not identified.
Mitochondrial
DNA
Copy Number Alterations in Human Cancers
Authors: Yu Man 
Published: April 2013

Abstract

Mitochondria are cytoplasmic organelles that participate in
adenosine triphosphate
(ATP) production through respiration and oxidative phosphorylation (OXPHOS), free radical formation and execution of apoptosis. Perturbation of mitochondrial function has been proposed as one vital hallmark of cancer cells. Besides plenty of germline and polymorphic sequence variations accumulated in both coding and noncoding regions of the mitochondrial genome (
mitochondrial deoxyribonucleic acid
(DNA); mtDNA), increased or reduced mtDNA copy number has also been increasingly described in a plethora of primary human malignancies. Altered mtDNA quantity may act as an important player in the multistep carcinogenesis of at least some types of human cancer by fuelling tumour initiation and/or advancement. In addition, mtDNA content turnover in bodily liquids from cancer patients could be exploited as a novel molecular tool for early cancer screening and diagnosis.

Key Concepts:

Disruption of mitochondrial function and the oxidative phosphorylation system may lead to cancer occurrence and development.

MtDNA copy number changes have been frequently observed in a wide range of human malignancies.

Aberrant mtDNA quantity is correlated with many key clinicopathological features of cancer patients.

Alterations in mtDNA copy number have potential to affect cancer cell behaviours

in vitro

and

in vivo

.

mtDNA content alterations could be considered as a novel biomarker for early cancer detection and diagnosis.
Microscopy of Graphene Growth, Processing, and Properties
Authors: Sutter Peter , Sutter Eli 
Published: April 2013

AbstractThe growth and properties of two‐dimensional (2D) materials–graphene as well as related monolayer systems, such as hexagonal boron nitride–on metals are topics of high scientific and technological interest. Real‐time low‐energy electron microscopy (LEEM) can provide unique insight into the fundamental growth mechanisms of 2D materials on metal substrates. In combination with in situ spectroscopic measurements, LEEM can greatly facilitate the search for synthesis and processing protocols that produce 2D materials with desired properties for applications. Here, progress is reviewed in understanding the scalable growth of high‐quality graphene on metals, novel processing strategies based on selective chemical reactions at the graphene/metal interface, and important materials properties (structure, electronic properties, work function, etc.) by surface microscopy and complementary methods, using graphene/ruthenium as a model system. The body of work shows that in situ microscopy can be used as a powerful tool for achieving and probing a wide range of functionalities in 2D materials.
Domain Wall Conduction and Polarization‐Mediated Transport in Ferroelectrics
Authors: Vasudevan Rama K. , Wu Weida , Guest Jeffrey R. , Baddorf Arthur P. , Morozovska Anna N. , Eliseev Eugene A. , Balke Nina , Nagarajan V. , Maksymovych Peter , Kalinin Sergei V. 
Published: April 2013

AbstractNanometer‐scale electronic transport in engineered interfaces in ferroelectrics, such as domains and topological defects, has emerged as a topic of broad interest due to potential applications in information storage, sensors and photovoltaic devices. Scanning probe microscopy (SPM) methods led to rapid growth in the field by enabling correlation of the unique functional properties with microstructural features in the aforementioned highly localized phenomena. In addition to conduction localized at interfaces, polarization‐mediated control of conduction through domains in nanoscale ferroelectrics suggests significant potential for use in memristor technologies. In parallel with experiment, theory based on thermodynamic Landau‐Ginzburg‐Devonshire (LGD) framework has seen rapid development, both rationalizing the observations, and hinting at possibilities for local, deterministic control of order parameters. These theories can successfully account for static interface conductivity at charged, nominally uncharged and topologically protected domain walls. Here, recent experimental and theoretical progress in SPM‐motivated studies on domain wall conduction in both standard and improper ferroelectrics are reviewed. SPM studies on transport through ferroelectrics reveal that both domains and topological defects in oxides can be exploited as individual elements for use in functional nanoscale devices. Future prospects of the field are discussed.
Nanosphere Lithography as a Versatile Method to Generate Surface‐Imprinted Polymer Films for Selective Protein Recognition
Authors: Bognár Júlia , Szűcs Júlia , Dorkó Zsanett , Horváth Viola , Gyurcsányi Róbert E. 
Published: April 2013

AbstractA versatile approach based on nanosphere lithography is proposed to generate surface‐imprinted polymers for selective protein recognition. A layer of 750 nm diameter latex bead‐protein conjugate is deposited onto the surface of gold‐coated quartz crystals followed by the electrosynthesis of a poly(3,4‐ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) film with thicknesses on the order of the bead radius. The removal of the polymer bead‐protein conjugates, facilitated by using a cleavable protein‐nanosphere linkage is shown to result in 2D arrays of periodic complementary size cavities. Here it is demonstrated by nanogravimetric measurements that the imprinting proceeds further at molecular level and the protein (avidin) coating of the beads generates selective recognition sites for avidin on the surface of the PEDOT/PSS film. The binding capacity of such surface‐imprinted polymer films is ca. 6.5 times higher than that of films imprinted with unmodified beads. They also exhibit excellent selectivity against analogues of avidin, i.e., extravidin, streptavidin, and neutravidin, the latter being in fact undetectable. This methodology, if coupled with properly oriented conjugation of the macromolecular template to the nanoparticles, offers the possibility of site‐directed imprinting.
Novel All‐Natural Microcapsules from Gelatin and Shellac for Biorelated Applications
Authors: Patel Ashok R. , Remijn Caroline , Cabero Ana‐isabel Mulet , Heussen Patricia C.M. , ten Hoorn Jack W.M. Seijen , Velikov Krassimir P. 
Published: April 2013

AbstractThe generation of novel all‐natural biopolymeric microcapsules fabricated using natural biopolymers, protein (gelatin) and resin (shellac), is reported. These novel microcapsules are generated using a simple extrusion method wherein the gelatin‐shellac mixture is dropped in an acidic medium resulting in an instantaneous solidification of aqueous drops into solid spherical microcapsules that retain their shape on air‐drying. The formation of the microcapsules is basically due to the strong interactions between two oppositely charged polymers (as confirmed from isothermal titration calorimetry and infrared spectroscopy) and the instant precipitation of acid‐resistant shellac. These novel microcapsules prepared without the help of any cross‐linkers or harsh solvent are extensively characterized and several biorelated applications for pharmaceuticals (encapsulation and release of bioactive molecules), foods (loading of colorants and flavors), sensors (encapsulation of pH sensitive dye), and biotechnology (enzyme immobilization) fields are further demonstrated.
Amphiphilic Polymeric Nanocarriers with Luminescent Gold Nanoclusters for Concurrent Bioimaging and Controlled Drug Release
Authors: Chen Dongyun , Luo Zhentao , Li Najun , Lee Jim Yang , Xie Jianping , Lu Jianmei 
Published: April 2013

AbstractMultifunctional theranostic systems with good biocompatibility, strong clinical imaging capability, and target specificity are the desired features of future medicine. Here, the design of a theranostic nanocomposite capable of simultaneous targeting and imaging of the cancer cells is presented. It releases its drug payload by a controlled release mechanism. The nanocomposite contains luminescent gold nanocluster (L‐AuNC) photostable and biocompatible diagnostic probes conjugated to a folic acid (FA)‐modified pH‐responsive amphiphilic polymeric system for controlled drug release. The nanocomposite uses a core‐satellite structure to encapsulate hydrophobic drugs and releases the drug payload in mildly acidic endosomal/lysosomal compartments by the action of the pH‐labile linkages in the polymer. In vivo studies show the selective accumulation of the FA‐conjugated nanocomposite in tumor tissues by folate‐receptor‐mediated endocytosis. These findings demonstrate the potential of the nanocomposite as a nontoxic, folate‐targeting, pH‐responsive drug carrier that is useful for the early detection and therapy of folate‐overexpressing cancerous cells.