bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transcription/
DNA
Repair Factor
TFIIH
Authors: Radu Laura , Maglott‐Roth Anne , Poterszman Arnaud
Published: April 2013

Transcription factor IIH (TFIIH) is a eukaryotic multicomponent macromolecular assembly composed of 10 subunits including two
deoxyribonucleic acid
(DNA)‐dependent helicase activities of opposite polarities and a
kinase
. Mutations in the helicases xeroderma pigmentosum group D protein (XPD) and xeroderma pigmentosum group B protein (XPB) as well as in the p8/TTD‐A subunit of human TFIIH are associated with three dramatic genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). Initially recognised as a basal factor responsible for transcription initiation of protein coding genes and transition from initiation to elongation, TFIIH also plays a critical role in nucleotide excision repair via its DNA‐opening helicase activity at the site of a lesion. A subcomplex, harbouring its kinase activity, phosphorylates the carboxy‐terminal domain (CTD) of
ribonucleic acid
(RNA) polymerase II as well as a number of transcription regulators including nuclear hormone receptors.

Key Concepts:

TFIIH is a prime example of multienzyme multitasking macromolecular assembly. Recent data suggest that several components are found in nonTFIIH complexes and that the function of TFIIH is regulated by its subunit composition.

The human transcription/DNA repair factor TFIIH is a multi‐subunit complex composed two functional and structural entities: core‐TFIIH consists of XPB, p62, p52, p44, p34 and p8, whereas the CDK‐activating kinase (CAK) subcomplex contains cyclin‐dependent kinase 7 (CDK7), cyclin H and MAT1. XPD bridges the core‐TFIIH to the CDK activating kinase (CAK) complex, which also exists as a free complex with a distinct function.

Although identified as a basal factor responsible for transcription initiation, TFIIH also plays a critical role in nucleotide excision repair and is implicated in the control of cell cycle progression.

Key insights into TFIIH result from investigations centred on the analysis of mutations identified in XP, CS and TTD patients.

Most mutations identified in patients reside within the noncatalytic regions of the helicases and do not affect the enzymatic activity of TFIIH
per se
but rather disturb the interactions of the catalytic subunits with their regulatory partners, impairing transcription and DNA repair.
Ethics of Complementary Medicine
Authors: Ernst Edzard
Published: April 2013

The ethical principles which apply to medicine in general also apply to complementary medicine (CM). However, the fact that CM is largely unregulated means that certain issues are of particular relevance to this area. These issues include the following: the use of ineffective procedures, the publication of misleading health claims, the misuse of titles, the lack of informed consent, the failure to monitor and report adverse effects, the nondisclosure of conflicts of interest and the fabrication of research. This article provides a brief outline of these themes.

Key Concepts:

Complementary medicine has to adhere to the same principles of ethics as any other type of medicine.

The unregulated nature of much of complementary medicine means that certain ethical issues are more relevant to complementary medicine than to other fields.

Despite the widespread use of complementary medicine, there has so far been relatively little attention to ethical issues in this area.
Molecular Genetics of
CHARGE
Syndrome
Authors: van Ravenswaaij‐Arts Conny M A , Hoefsloot Lies H
Published: April 2013

Coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital abnormalities and ear abnormalities and deafness (CHARGE) syndrome is a highly variable, multiple congenital anomaly syndrome with an estimated prevalence of 1 in 17 000. The main features are hypoplasia of the semicircular canals, coloboma, choanal atresia, heart defects, hypogonadotropic hypogonadism, ear malformations, deafness, cranial nerve dysfunction and cleft/lip palate. The phenotype shows a remarkable variability that cannot be explained by different genotypes. In most patients a

de novo

autosomal dominant loss‐of‐function mutation of chromodomain helicase
deoxyribonucleic acid
(DNA)‐binding gene 7 (
CHD7
) is found. The CHD protein family plays a role in transcription regulation by chromatin remodelling. Expression studies as well as studies in stem cells, neural crest cells and animal models have revealed that CHD7 has a tissue‐ and embryonic stage‐specific function in enhancer‐mediated transcription. The broad phenotypic spectrum involving many organ systems that is seen in CHD7 haploinsufficiency can be explained by cell type‐specific binding sites, protein complexes and target genes of CHD7.

Key Concepts:

CHARGE syndrome is a multiple congenital anomaly syndrome with a highly variable and broad clinical spectrum.

CHARGE syndrome shows remarkable clinical overlap with other multiple congenital anomaly syndromes. In contrast,
CHD7
mutations do not cause nonsyndromic congenital defects.

CHD7
is the main causal gene in CHARGE syndrome and codes for a chromodomain protein.

Chromodomain proteins are important during embryonic development.

CHD7 has a function in enhancer‐mediated transcription.

Both the expression of CHD7 and its binding sites to genomic enhancer regions are cell type‐ and embryonic stage‐dependent.

CHD7 haploinsufficiency alters transcription of tissue‐specific target genes that are normally regulated by CHD7 or complexes in which CHD7 is involved.

CHD7 plays an important role in neural crest cells and the interaction of the neural crest with other tissues.

Investigation of overlapping phenotypes and converging molecular pathways gives insight into the pathogenesis.
Molecular Genetics of Alkaptonuria
Authors: Zatkova Andrea
Published: April 2013

Alkaptonuria (AKU), the first defined human genetic disease with a recessive trait, is caused by mutations within the homogentisate1,2‐dioxygenase(HGD) gene (3q13.33). This prototypic inborn error of metabolism is characterised by typical bluish‐black pigmentation in connective tissue ochronosis and severe form of osteoarthritis caused by the deposition of ochronotic pigment in the joints. AKU belongs to a group of rare diseases (1:250 000–1:1 000 000), however, several ethnities were reported, where an increased incidence of AKU was observed (Slovakia, Dominican Republic, Jordan and India). Mutation analysis was so far performed in approximately 350 out of more than 650 worldwide reported AKU patients. Rather high heterogeneity was observed with 122 AKU‐causing mutations that are listed together with HGD polymorphisms in the global HGD mutation database (http://hgddatabase.cvtisr.sk/). Because HGD enzyme functions as hexamer, dimer of trimers, genotype/phenotype correlations are difficult to perform in this rare disease.

Key Concepts:

Alkaptonuria (AKU) is a prototypic inborn error in the metabolism of phenylalanine and tyrosine, characterised by the inability to metabolise homogentisic acid (HGA).

The raised HGA levels in plasma and extracellular fluid lead to ochronosis, the deposition of polymers of HGA as pigment (ochronotic pigment) in connective tissues including cartilage, heart valves and sclera.

Ochronosis leads to painful destruction of large weight‐bearing joints as well as fusion of the vertebrae, scoliosis and tendon and ligament ruptures.

AKU is caused by homozygous or compound heterozygous mutations in the homogentisate‐1,2‐dioxygenase gene (HGD) mapping to the chromosome 3q13.33.

AKU belongs to a group of rare diseases (1:250 000–1:1 000 000), however, several ethnities were reported, where an increased incidence of AKU was observed (Slovakia, Dominican Republic, Jordan and India).

In approximately 350 patients reported worldwide so far 122 differentHGDmutations have been reported.

It was also shown that AKU is caused also by the apparently partial loss‐of‐function mutations, however, the heterozygous carriers of AKU are healthy.

HGDhaplotype analysis helps to identify the origin of individual AKU‐causing mutations in different countries.

The triketone herbicide nitisinone or Orfadin inhibits the 4‐hydroxyphenylpyruvate dioxygenase enzyme, which produces HGA, thus, it can decrease HGA and should therefore potentially be able to modify AKU.

It has been shown that AKU is a novel type II AA amyloidosis, which opens new important perspectives for its therapy, since the control of the underlying inflammatory disorder can result in regression of the disease.

Research on ochronosis in this monogenic disease can help to elucidate the molecular pathogenesis of the more common varieties of osteoarthritis, particularly the biochemical and structural changes at its initial stages.
Genetics of Carney Complex
Authors: Horvath Anelia , Stratakis Constantine A
Published: April 2013

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

Choroideremia (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

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

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

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

Simpson‐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

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

In 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

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

The 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

Nanometer‐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

A 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

The 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

Multifunctional 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.
Life at the interface: Adults with “pediatric” disorders of the nervous system
Authors: Schor Nina F.
Published: April 2013

The increasing longevity of patients with congenital and developmental disorders of the nervous system reflects the palliative and social success of pediatrics in the past 2 decades. This success has resulted in an increasing number of adult patients with residua or sequelae of childhood disease and/or its treatment. It is critically important that residencies and subspecialty fellowships train a cadre of physicians to prepare patients and families for the transition of children with special health care needs to adulthood and to attend to their unique medical, psychological, and social concerns. Health services and education research must better define the needs of this growing population and the best ways to educate their physicians and families and empower them to become as independent as their fullest potential allows. Ann Neurol 2013;74:158–163
Uniaxial tensile properties of TiO2 coated single wool fibers by sol‐gel method: The effect of heat treatment
Authors: Aksakal Baki , Koc Kenan , Bozdogan Altan , Tsobkallo Katherina
Published: April 2013

Single wool fibers were coated with TiO2 by using the sol‐gel method. The uniaxial tensile properties of TiO2 coated single wool fibers heated at different temperatures from 25 to 200°C were investigated and compared with those of uncoated single wool fibers. It was observed that the shape of the stress–strain curve of TiO2 coated wool fibers became the same as uncoated wool fibers and showed a similar tendency of change to uncoated wool fibers with increasing temperature. But, the TiO2 coated wool fibers obtained higher rigidity than uncoated wool fibers and up to their rupture points; they obtained higher stress levels in three deformation regions in the stress–strain curves, which indicates stronger wool fibers. Although the breaking extension of TiO2 coated wool fibers decreased little by about 8%, the Young's modulus of TiO2 coated wool fibers increased significantly by 19%, which was caused mostly by an increment in the stiffness of the cuticle layer of the wool fiber, and remained relatively higher than that of uncoated wool fibers after heat treatments. Structural changes in both uncoated and TiO2 coated single wool fibers due to thermal effect, which caused the changes in the uniaxial tensile properties and the thermal behaviors of these fibers were discussed by using spectroscopic and thermal analysis methods in detail. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 898‐907, 2013
Does it matter who your schoolmates are? An investigation of the association between school composition, school processes and mathematics achievement in the early years of primary education
Authors: Boonen Tinneke , Speybroeck Sara , de Bilde Jerissa , Lamote Carl , Van Damme Jan , Onghena Patrick
Published: April 2013

Although many studies have focused on the importance of school composition for student achievement, there is still no consensus on whether school composition matters to student achievement, and, if so, why. Therefore, the present study investigates the association between school composition and mathematics achievement at the end of second grade in Flanders. International research points to the initial ability level, SES, ethnicity and sex composition of the school as potential variables in explaining differences in student achievement. Moreover, some researchers suggest that schools ‘react’ to their student body and for that reason we investigated the possible association between school composition and school processes. Data from the SiBO Project have been analyzed using multilevel regression and multilevel mediation analysis. The results showed no direct school composition effects with respect to prior achievement, SES, ethnicity and sex on math achievement. We found two small differential effects, indicating that mean school prior achievement seems to positively affect initially high achievers, and the proportion of minority students in school seems to negatively affect students speaking a non‐European language except for Turkish, Arabic or Berber at home. Furthermore, two small indirect effects were found which suggest that schools with a high mean prior achievement or a high mean SES keep in regular contact with their students' parents and this, in turn, appears to enhance students' math achievement. Overall, our results seem to indicate that school composition in the early years of primary education hardly matters.
Pausing for thought: Disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis
Authors: Jennings Barbara H.
Published: April 2013

Factors affecting transcriptional elongation have been characterized extensively in in vitro, single cell (yeast) and cell culture systems; however, data from the context of multicellular organisms has been relatively scarce. While studies in homogeneous cell populations have been highly informative about the underlying molecular mechanisms and prevalence of polymerase pausing, they do not reveal the biological impact of perturbing this regulation in an animal. The core components regulating pausing are expressed in all animal cells and are recruited to the majority of genes, however, disrupting their function often results in discrete phenotypic effects. Mutations in genes encoding key regulators of transcriptional pausing have been recovered from several genetic screens for specific phenotypes or interactions with specific factors in mice, zebrafish and flies. Analysis of these mutations has revealed that control of transcriptional pausing is critical for a diverse range of biological pathways essential for animal development and survival.
BRIEF REPORT: LATENCY FUNCTIONAL ANALYSIS OF ELOPEMENT
Authors: Davis Tonya N. , Durand Shannon , Bankhead Jenna , Strickland Erica , Blenden Kara , Dacus Sharon , Hannig Alyssa Pond , Haupert Megan , Fuentes Lisa , Machalicek Wendy
Published: April 2013

Elopement is a potentially dangerous problem behavior prevalent among individuals with developmental disabilities. However, functional analysis of elopement presents unique challenges including potential confounds because of the need for participant retrieval during functional analysis sessions. In the current study, we implemented a latency functional analysis with an eight‐year‐old child with an intellectual disability, in which the dependent measure was latency to elopement. Following the latency functional analysis, a functional communication intervention was developed and its effectiveness in decreasing elopement was evaluated using an ABAB design. Findings suggest that a functional analysis of latency may be a suitable methodology to identify the operant function of elopement. Copyright © 2013 John Wiley & Sons, Ltd.
Preparation of water‐soluble CdSe quantum dots and its application for nitrite detection in the anodic electrochemiluminescence
Authors: Yao Xun , Yan Panpan , Zhang Kai , Li Jianguo
Published: April 2013

Water‐soluble CdSe quantum dots (QDs) have been prepared by using L‐cysteine as the stabilizer in an aqueous phase under the optimized conditions. The characteristics and shapes of CdSe QDs have been proposed on the basis of UV‐Vis and fluorescence spectra. A rapid analytical method for electrochemiluminescence (ECL) determination of nitrite has been developed on the basis of the quenching effect on anodic ECL emission of CdSe QDs under the optimum experimental conditions. In a neutral system and at a relatively low potential (+0.960 V), the ECL emission of CdSe QDs could be greatly enhanced by sulfite and could be gradually quenched by nitrite at an indium tin oxide (ITO) electrode. The proposed method may allow the measurement of nitrite ranging from 1 μM to 0.5 mM with a correlation coefficient of 0.9956 (n = 10) and a detection limit of 0.2 μM (3σ), and the relative standard deviation for 10 μM nitrite (n = 9) is 1.72 %. The proposed method could be adopted for the sensitive detection of ECL quenchers by using nitrite as a model molecule. Copyright © 2013 John Wiley & Sons, Ltd.
Transgastric appendicectomy
Authors: Kaehler G , Schoenberg M B , Kienle P , Post S , Magdeburg R
Published: April 2013

Background

Experimental studies and small anecdotal reports have documented the potential and feasibility of transgastric appendicectomy. This paper reports the results of the new technique in a selected group of patients.

Methods

From April 2010 transgastric appendicectomy was offered to all patients with acute appendicitis, but without generalized peritonitis or local contraindications.

Results

Of 111 eligible patients 15 agreed to undergo the transgastric operation. After conversion of the first case to laparoscopy because of severe inflammation and adhesions, the following 14 consecutive transgastric procedures were completed. Two patients with initial peritonitis required laparoscopic lavage 4 days after transgastric appendicectomy, but no leaks were detected at the appendiceal stump or stomach.

Conclusion

These preliminary results have shown the feasibility of this innovative procedure. Additional studies, however, are required to demonstrate the specific advantages and disadvantages of this approach, and define its role in clinical surgery.
Simultaneous quantification of paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin from Si‐Ni‐San extract in rat plasma and tissues by liquid chromatography–tandem mass spectrometry
Authors: Li Tianxue , Yan Zhixiang , Zhou Chen , Sun Jian , Jiang Chuan , Yang Xinghao
Published: April 2013

In this study, a sensitive and reliable liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the determination of seven bioactive components including paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin in rat plasma and tissues after oral administration of Si‐Ni‐San extract using astragaloside IV as internal standard (IS). The plasma and tissue samples were extracted by solid‐phase extraction. Chromatographic separation was accomplished on a C18 column with a multiple‐step gradient elution. The quantification was obtained by scanning with multiple reaction monitoring via an electrospray ionization source that was operated by switching between the positive and negative modes in two MS/MS scan segments. Full validation of the assay was implemented. In conclusion, this method demonstrated good linearity and specificity. The lower limits of quantification for the analytes were <7.5 ng/mL. Intra‐ and inter‐day precisions (RSD) were <12.5% and accuracy (RE) ranged from −10.2 to 7.3%. The average recoveries of the analytes from rat plasma and tissues were >65.2% and 58.6%, respectively. The validated method was further applied to the determination of actual rat plasma and tissues after oral administration of Si‐Ni‐San extract. The results provided a meaningful basis for the clinical application of this prescription. Copyright © 2013 John Wiley & Sons, Ltd.
Chemotaxonomic Importance of the Essential‐Oil Composition in Two Subspecies of Teucrium stocksianumBoiss. from Iran
Authors: Sonboli Ali , Bahadori Mir Babak , Dehghan Hossein , Aarabi Leila , Savehdroudi Parisa , Nekuei Mina , Pournaghi Narges , Mirzania Foroogh
Published: April 2013

The hydrodistilled essential oils obtained from aerial flowering parts of Teucrium stocksianum ssp. stocksianum (TSS) and T. stocksianum ssp. gabrielae (TSG) from Iran were analyzed by capillary GC and GC/MS. The oil analysis of two subspecies led to the identification of 65 compounds that accounted for 93.3 and 95.1% of the total oil compositions, respectively. Sesquiterpenoids (52.9%) constituted the main compounds in the essential oil of TSS represented mainly by cis‐sesquisabinene hydrate (12.0%), followed by epi‐β‐bisabolol (6.6%), guaiol (5.4%), and β‐eudesmol (4.4%), whilst monoterpenoids (61.2%) were found to be the major components of the oil of TSG, represented by α‐pinene (23.0%), β‐pinene (13.0%), myrcene (6.3%), and sabinene (6.3%). The principal component in both subspecies, TSS and TSG, was α‐pinene (22.0 and 23.0%, resp.) and β‐pinene (6.5 and 13.0%, resp.). epi‐α‐Cadinol, myrcene, and sabinene, which were detected as principal compounds of TSG, were characterized in lower amounts (<1.5%) in the oil of TSS. Seven components were identified in the oil of TSS corresponding to 25.9% of total oil, which were totally absent in the oil of TSG, of which cis‐sesquisabinene hydrate (12.0%), guaiol (5.4%), and β‐eudesmol (4.4%) were in considerable amounts. Taxonomic position of the subspecies is discussed on the basis of phytochemical data.
Kolbe‐Schmitt Flow Synthesis in Aqueous Solution – From Lab Capillary Reactor to Pilot Plant
Authors: Krtschil U. , Hessel V. , Kost H.‐J. , Reinhard D.
Published: April 2013

Significant process intensification was achieved for the continuously operated Kolbe‐Schmitt synthesis of 2,4‐dihydroxybenzoic acid (β‐resorcylic acid) on laboratory scale by using different approaches opening novel process windows. The results of the optimal process variant, both from the economic and ecological view, were scaled up to the pilot scale. In a first step, the synthesis from resorcinol in aqueous potassium hydrogen carbonate solution was transferred from the capillary reactor to a tailor‐made electrically heated microstructured reactor comprising 40 microchannels and enabling a 25‐fold increase of the capacity. In a second step, a pilot plant comprising three of such reactors operated in parallel was built and successfully tested with the same reaction.
ChemInform Abstract: Na3SbS3: Single Crystal X‐Ray Diffraction, Raman Spectroscopy, and Impedance Measurements.
Authors: Pompe Constantin , Pfitzner Arno
Published: April 2013

Pale yellow and air and moisture sensitive Na3SbS3 is prepared by reaction of stoichiometric mixtures of Na2S, Sb, and S (graphite‐coated silica tube, 1.
ChemInform Abstract: The Synthesis and Thermal Stability of CaKCe(PO4)2 Phosphate. Phase Equilibria in the CaKPO4—CePO4 System.
Authors: Matraszek Aleksandra , Szczygiel Irena , Znamierowska Teresa
Published: April 2013

CaKCe(PO4)2 (I) is prepared by solid state sintering of stoichiometric mixtures of CePO4 and CaKPO4 (1.
ChemInform Abstract: Crystal Structure Modeling, Electrical and Thermal Characterization of Triple Molybdates RbCrTi0.5(MoO4)3 (R: Fe, Cr).
Authors: Dorzhieva Sesegma G. , Bazarov Bair G. , Subanakov Alexey K. , Bazarova Jibzema G.
Published: April 2013

The new compounds RbMTi0.5(MoO4)3 (M: Fe, Cr) are prepared by solid state reactions of Rb2MoO4, M2(MoO4)3, MoO3, and TiO2 (porcelain crucible, 580—600 °C, 70—100 h).
ChemInform Abstract: Syntheses, Crystal Structures, and Twinning of the Isotypic Rare‐Earth Metal Bromide ortho‐Oxidomolybdates LaBrMoO4 and CeBrMoO4.
Authors: Hartenbach Ingo , Henning Harald , Schleid Thomas , Schustereit Tanja , Strobel Sabine
Published: April 2013

The title compounds are synthesized by solid‐state reactions of Ln2O3 (Ln: La, Ce), LnBr3, and MoO3 in molar ratios of 1:1:3 (820°C, 7 d).
ChemInform Abstract: Zirconocene Dichloride Catalyzed Hydrodefluorination of C(sp2)—F Bonds.
Authors: Yow Shuhui , Gates Sarah J. , White Andrew J. P. , Crimmin Mark R.
Published: April 2013

Four‐coordinate diketiminate‐stabilized aluminum dihydrides are found to be effective terminal reductants in the zirconocene‐catalyzed dehydrofluorination of fluoroarenes (yields determined by NMR).
ChemInform Abstract: Chiral Picolylamines for Michael and Aldol Reactions: Probing Substrate Boundaries.
Authors: Nugent Thomas C. , Bibi Ahtaram , Sadiq Abdul , Shoaib Mohammad , Umar M. Naveed , Tehrani Foad N.
Published: April 2013

A new primary‐tertiary bifunctional organocatalyst, which can be further fine‐tuned, is developed for the title reactions.