bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Assurance and Quality Control in Clinical Cytogenetics
Authors: Mikhail Fady M. , Watson Michael S.
Published: July 2014

The goal of any clinical laboratory should be to provide patients with the most accurate test results possible. This is accomplished through various overlapping programs that continuously monitor and optimize all aspects of a test, including decisions by the laboratory to offer a test, the decision of providers to request the test, the testing itself, and the reporting of results to the referral source and patient. The levels at which test performance and accuracy can be optimized are encompassed under quality control (QC) and quality assurance (QA). The monitoring of QC and QA problems allows for the integration of these parameters into a total quality management program. This unit reviews QC and QA guidelines, in addition to discussing how to establish a quality assurance program. Curr. Protoc. Hum. Genet. 82:8.2.1‐8.2.10. © 2014 by John Wiley & Sons, Inc.
Quantitative study on experimentally observed poroelastic behavior of Berea sandstone in two‐phase fluid system
Authors: Goto Hiroki , Aichi Masaatsu , Tokunaga Tomochika , Yamamoto Hajime , Ogawa Toyokazu , Aoki Tomoyuki
Published: July 2014

Coupled two‐phase fluid flow and poroelastic deformation of Berea sandstone is studied through laboratory experiment and numerical simulation. In the experiment, compressed air was infiltrated from the bottom of a water‐saturated cylindrical Berea sandstone sample under hydrostatic external stress condition. Both axial and circumferential strains at half the height of the sample showed sudden extension and monotonic and gradual extension afterward. Numerical simulation based on thermodynamically consistent constitutive equations was conducted in order to quantitatively analyze the experimental results. In a simulation assuming isotropy of material properties, the volumetric discharge rate of water at the outlet and one of the axial, circumferential, and volumetric strains at half the height of the sample were reproduced well by each parameter set, while the other two strains were not. When introducing transverse isotropy, all the experimental data were reproduced well. In addition, the effect of saturation dependency of Bishop's effective stress coefficient on the deformation behavior of porous media was discussed, and it was found that strains, both axial and circumferential, are sensitive to the coefficient.
Forward propagation of the Zagros Simply Folded Belt constrained from magnetostratigraphy of growth strata
Authors: Ruh Jonas B. , Hirt Ann M. , Burg Jean‐Pierre , Mohammadi Ali
Published: July 2014

The temporal evolution of the Zagros Simply Folded Belt is constrained by a magnetostratigraphic sequence containing a progressive unconformity on the southern limb of the Kuh‐e Ghol Ghol anticline, in the Central Fars. The investigated ~1400 m thick sequence exposes a regressive megacycle containing, from bottom to top, open and shallow marine marls and sandy limestones, fine‐ to coarse‐grained fluvial deposits and alluvial conglomerates. Correlating the magnetostratigraphic section with the geomagnetic polarity time scale constrains the transition from marine to fluvial sediment deposition at ~6 Ma. This transition was accompanied by a change in the accumulation rate from ~15 cm/ka to ~40 cm/ka, as measured on lithified sediments. Alluvial river deposits first occurred at ~3.2 Ma. The Kuh‐e Ghol Ghol anticline began to grow at ~3.8 Ma, witnessing fastest limb rotation rates of 40°/Ma at ~3.3 Ma. Reporting magnetostratigraphic sections and ages of growth strata on a map of NE Fars reveal an ~1 cm/a, southwestward migration rate of the deformation front during the middle and late Miocene.
Nonequilibrium water dynamics in the rhizosphere: How mucilage affects water flow in soils
Authors: Kroener Eva , Zarebanadkouki Mohsen , Kaestner Anders , Carminati Andrea
Published: July 2014

The flow of water from soil to plant roots is controlled by the properties of the narrow region of soil close to the roots, the rhizosphere. In particular, the hydraulic properties of the rhizosphere are altered by mucilage, a polymeric gel exuded by the roots. In this paper we present experimental results and a conceptual model of water flow in unsaturated soils mixed with mucilage. A central hypothesis of the model is that the different drying/wetting rate of mucilage compared to the bulk soil results in nonequilibrium relations between water content and water potential in the rhizosphere. We coupled this nonequilibrium relation with the Richards equation and obtained a constitutive equation for water flow in soil and mucilage. To test the model assumptions, we measured the water retention curve and the saturated hydraulic conductivity of sandy soil mixed with mucilage from chia seeds. Additionally, we used neutron radiography to image water content in a layer of soil mixed with mucilage during drying and wetting cycles. The radiographs demonstrated the occurrence of nonequilibrium water dynamics in the soil‐mucilage mixture. The experiments were simulated by numerically solving the nonequilibrium model. Our study provides conceptual and experimental evidences that mucilage has a strong impact on soil water dynamics. During drying, mucilage maintains a greater soil water content for an extended time, while during irrigation it delays the soil rewetting. We postulate that mucilage exudation by roots attenuates plant water stress by modulating water content dynamics in the rhizosphere.
Formation and geomorphologic history of the Lonar impact crater deduced from in situ cosmogenic 10Be and 26Al
Authors: Nakamura Atsunori , Yokoyama Yusuke , Sekine Yasuhito , Goto Kazuhisa , Komatsu Goro , Kumar P. Senthil , Matsuzaki Hiroyuki , Kaneoka Ichiro , Matsui Takafumi
Published: July 2014

The Lonar impact crater is one of a few craters on Earth formed directly in basalt, providing a unique opportunity to study an analog for crater degradation processes on Mars. Here we present surface 10Be and 26Al exposure dates in order to determine the age and geomorphic evolution of Lonar crater. Together with a 14C age of preimpact soil, we obtain a crater age of 37.5 ± 5.0 ka, which contrasts with a recently reported and apparently older 40Ar/39Ar age (570 ± 47 ka). This suggests that the 40Ar/39Ar age may have been affected by inherited radiogenic 40Ar (40Ar*inherited) in the impact glass. The spatial distribution of surface exposure ages of Lonar crater differs from that for Barringer crater, indicating Lonar crater rim is actively eroding. Our new chronology provides a unique opportunity to compare the geomorphological history of the two craters, which have similar ages and diameters, but are located in different climate and geologic settings.
Seismicity, faulting, and structure of the Koyna‐Warna seismic region, Western India from local earthquake tomography and hypocenter locations
Authors: Dixit Madan M. , Kumar Sanjay , Catchings R. D. , Suman K. , Sarkar Dipankar , Sen M. K.
Published: July 2014

Although seismicity near Koyna Reservoir (India) has persisted for ~50 years and includes the largest induced earthquake (M 6.3) reported worldwide, the seismotectonic framework of the area is not well understood. We recorded ~1800 earthquakes from 6 January 2010 to 28 May 2010 and located a subset of 343 of the highest‐quality earthquakes using the tomoDD code of Zhang and Thurber (2003) to better understand the framework. We also inverted first arrivals for 3‐D Vp, Vs, and Vp/Vs and Poisson's ratio tomography models of the upper 12 km of the crust. Epicenters for the recorded earthquakes are located south of the Koyna River, including a high‐density cluster that coincides with a shallow depth (<1.5 km) zone of relatively high Vp and low Vs (also high Vp/Vs and Poisson's ratios) near Warna Reservoir. This anomalous zone, which extends near vertically to at least 8 km depth and laterally northward at least 15 km, is likely a water‐saturated zone of faults under high pore pressures. Because many of the earthquakes occur on the periphery of the fault zone, rather than near its center, the observed seismicity‐velocity correlations are consistent with the concept that many of the earthquakes nucleate in fractures adjacent to the main fault zone due to high pore pressure. We interpret our velocity images as showing a series of northwest trending faults locally near the central part of Warna Reservoir and a major northward trending fault zone north of Warna Reservoir.
m
RNA
Stability
Authors: Kaberdin Vladimir , Bläsi Udo
Published: July 2014

The steady‐state level of a
messenger ribonucleic acid (mRNA)
is determined by both its rate of synthesis and degradation. The degradation of mRNA is an important tool employed by cells to control gene expression and to adjust the level of protein synthesis in response to physiological needs or environmental signals. The degradation of mRNA in all organisms is mastered by a rather restricted number of enzymes with major (endo‐ and exoribonucleases) and ancillary (e.g. RNA helicases) functions. Some of these enzymes are phylogenetically conserved across the three domains of life – bacteria, archaea and eukarya. Moreover, the main components of the RNA decay machinery can associate with each other to form multienzyme complexes, which enable to coordinate and control mRNA decay
in vivo
. This review provides a brief overview on the major factors and mechanisms involved in bacterial and eukaryal mRNA degradation.

Key Concepts:

The stability of individual mRNAs varies and is dependent on intrinsic properties (i.e. specific structure and sequence) of transcripts.

The enzymes and factors involved in mRNA decay in prokaryotes and eukaryotes can associate with each other to form multienzyme complexes such as degradosomes or exosomes

Mechanisms of mRNA decay in pro‐ and eukaryotes share many common steps.

Pro‐ and eukaryotic cells use specific mechanisms to eliminate defective mRNAs.

Numerous noncoding RNAs control mRNA decay in pro‐ and eukaryotes.
Protein‐Derived Cofactors
Authors: Davidson Victor L
Published: July 2014

Protein‐derived cofactors are catalytic or redox‐active centres in proteins that are formed by covalent irreversible posttranslational modification of one or more amino acid residues. The mechanisms by which these posttranslational modifications are catalysed are quite diverse. In some cases, these modifications occur autocatalytically, and in other cases, they are enzyme catalysed. The formation of protein‐derived cofactors expands the range of chemical reactions that may be catalysed by enzymes in the absence of exogenous metal or organic cofactors. Protein‐derived cofactors typically function as electrophiles in catalysis and sometimes stabilise free‐radical intermediates or mediate biological electron transfer. This article describes the structures and functions of several protein‐derived cofactors and the diverse mechanisms of posttranslational modification through which they are generated.

Key Concepts:

Protein‐derived cofactors are formed by irreversible posttranslational modification of amino acid residues.

Protein‐derived cofactors typically serve as electrophiles or stabilise free radicals during enzyme catalysis.

Amino acid residues may acquire new catalytic or redox functions from posttranslational modification.

Modification of amino acids that provide ligands for metals can alter the properties of metalloenzymes.

Protein‐derived cofactors may be formed by a variety of autocatalytic and enzyme‐catalysed processes.
Enzymatic Rate Enhancements
Authors: Quinn Daniel M , Sikorski R Steven
Published: July 2014

Enzymatic rate enhancements arise from the unmatched ability of enzymes to stabilise the transition states of the reactions that they catalyse. Comparison of rate constants of an enzyme‐catalysed reactions, that is,kcatandkcat/Km, to that of the corresponding reaction in the absence of the enzyme, that is,kN, provides quantitative measures of enzyme catalytic power. Moreover, the ratio ofkNtokcat/Kmprovides a quantitative measure of transition state stabilisation effected by enzymes, which in turn motivates the development of ultrapotent transition state analogue enzyme inhibitors. The purpose of this article is to discuss the magnitude and mechanistic origins of enzymatic rate enhancements. Selected enzymes are described that manifest a wide range of rate enhancements and corresponding catalytic strategies. Factors that affect the evolution of enzyme catalytic power are presented.

Key Concepts:

A catalyst is a species that accelerates a chemical reaction without affecting the equilibrium constant of the reaction.

Enzymes are catalysts that accelerate chemical reactions that are necessary for life.

The quantitative degree to which an enzyme accelerates a chemical reaction is a measure of the catalytic power of the enzyme.

Enzymes derive their catalytic power from their marked abilities to stabilise the transition state(s) of the reactions that they catalyse.

Enzymic catalytic power is quantitated as the ratio of rate constants of enzyme‐catalysed reactions to the rate constants for the corresponding reactions in the absence of enzyme.

Enzymes whose catalytic power is highly evolved operate at the speed limit of biological catalysis; that is, they are diffusion controlled.
Caps on Eukaryotic mRNAs
Authors: Furuichi Yasuhiro
Published: July 2014

A 5′‐terminal cap is added to most eukaryotic cellular and viralmessenger ribonucleic acids (mRNAs)at an early stage of transcription. Capping is essential and modulates several subsequent events in gene expression including pre‐mRNA splicing, 3′‐poly(A) addition, overall stability, nuclear exit to cytoplasm, protein synthesis, and mRNA turnover initiated by decapping. These and other effects involve cap‐binding proteins that recognise the m7GpppN cap structure. Capping proceeds by a similar series of enzymatic steps in a wide range of systems, but differences exist between metazoans and unicellular eukaryotes and viruses, pointing to capping enzymes as potential targets for the development of selective drugs against some fungal, viral and parasitic infections. Moreover, the unique structural features of caps enable us to define the initiation sites and promoter regions of gene transcription, and provide a basis for advanced sequencer‐mediated high‐throughput genome‐wide profiling of gene expression in a wide range of cell types.

Key Concepts:

mRNA caps are now known to be essential components of gene expression in eukaryotic organisms.

The history of the discovery of the presence of 5′ caps on messenger RNA and its subsequent scientific flowering is a good example of how a seemingly small biochemical observation can lead to the deeper understanding of a wide range of fundamental molecular biological phenomena.

Evolution has resulted in wide variations in capping structure and function among organisms ranging from viruses to humans; the selective forces underlying such variation requires more research.

Research that has documented viral‐specific capping reactions in viruses should prove to be a fertile source of research leading to new and novel anti‐viral agents.

The ‘cap‐snatching’ strategies of influenza viruses is a remarkable example of an apparent adaptation to enhance infectivity and is a particularly compelling target for therapeutic intervention.

The NMD mRNA surveillance pathway, which includes a pioneer round of translation with cap‐binding proteins, results in a striking decrease of defective mRNA in cells of patients with genetic diseases containing premature termination codons.

Methylation of genomic DNA and mRNA is now widely accepted as a major pathway of the regulation of both transcription and translation in eukaryotes.

Protein synthesis is a major field of gene expression where many players work for mRNA capping, decapping, decoding, quality control of gene transcripts and peptide elongation.

Micro RNAs are now widely accepted as major players in the translational control of protein synthesis.

The analysis of cap‐trapped sequences by high‐throughput sequencers enables one to carry out a genome‐wide identification of promoters together with quantification of their expression, thus elucidating a promoter‐based network of transcriptional regulation.
Semliki Forest Virus
Expression System
Authors: Sjöberg Mathilda
Published: July 2014

The
Semliki Forest virus
(SFV) expression system utilises the efficient replication of SFV to transiently express foreign proteins in eukaryotic cells. In the basic version, cells are infected with a recombinant SFV where the part of the viral
ribonucleic acid (RNA)
genome that encodes the virus structural proteins is replaced by a gene of interest (transgene). On infection the viral genome is amplified and efficiently translated in the host cell cytoplasm, resulting in high‐level expression of the transgene. Recombinant virus is produced by co‐transfection of recombinant viral genomes and a helper genome that provides the virus structural proteins. Alternatively, infection is initiated by transfection with viral RNA genomes produced
in vitro
. Further developments, aiming for vaccine and therapeutic applications, include a
deoxyribonucleic acid (DNA)
vector where the recombinant SFV genome is placed under a
cytomegalovirus
promoter. This allows transgene expression without involving the structural virus proteins, and avoids RNA work
in vitro
.

Key Concepts:

A polylinker is a short DNA sequence containing multiple unique restriction sites.

A packaging signal is a motif in the viral genome that specifically interacts with the capsid forming protein of the virus. This will ensure efficient genome incorporation.

Replicon RNA is self‐replicating RNA that directs efficient production of protein.

Recombinant SFV is a suicide virus that infect cells and delivers replicon RNA but cannot produce new virions.

An autoprotease is a single use enzyme that is synthesised as part of a polyprotein and will release itself from the growing polypeptide chain.
Ecotoxicology
Authors: Calow Peter , Forbes Valery E
Published: July 2014

Ecotoxicology is the description and understanding of impacts of industrial and agricultural chemicals on ecological systems. It is to be distinguished from toxicology because it focuses on the impacts of chemicals on ecological groupings of organisms rather than on individuals; i.e. on populations, communities and ecosystems. Ecotoxicity tests that focus on the responses of individual organisms to toxic chemicals may not translate straightforwardly to relevant effects on ecological systems. Mathematical models can assist in making these extrapolations from organisms to ecological systems. Ecotoxicology plays a key part in informing ecological risk assessment and hence in the management of the production, use and disposal of industrial and agricultural chemicals.

Key Concepts:

Ecotoxicology is a science that is concerned with the effects of industrial and agricultural chemicals on ecological systems.

Though derived from toxicology, ecotoxicology is concerned less with the responses of individuals to chemicals and more with their effects on populations, communities and ecosystems.

Contaminating chemicals have their first impacts on the molecular and cellular systems within organisms but some of these may be nullified by homeostatic processes and ecological compensation. Others may be magnified by cascading processes. So the relationship between effects observed in tests that focus on individuals and ecological‐level responses is not straightforward.

It is important to distinguish between contamination (presence of chemicals in the environment) and pollution (presence of chemicals with adverse effects).

It is important to distinguish between hazard (the potential of chemicals to cause harm) and risk (the likelihood of that potential being realised).

Ecotoxicology plays a key part in informing the assessment of risks from chemicals to ecological systems and hence in managing their impacts.

Sensible risk management of chemicals is important because despite their potential to cause harm to ecosystems, chemicals make many contributions to human welfare, for example, in medicine and agricultural production.
Macrophages in Lipid and Immune Homeostasis
Authors: Neyen Claudine D , Gordon Siamon
Published: July 2014

Many components of the immune system play diverse roles in lipid metabolism and vice versa. Macrophage immune functions, including pathogen clearance and apoptotic cell removal, depend on recognition of lipid ligands by surface and intracellular immune receptors and secreted lipid‐binding molecules. Engagement of lipid receptors triggers an immune response, which is accompanied by
de novo
synthesis of bioactive lipids that help resolve inflammation. Oxidised lipids, byproducts of the oxidative burst, activate nuclear receptors, which not only orchestrate lipid homoeostasis but also cross‐regulate NFκB‐driven immune responses. Activation of macrophages leads to cytokine production and induction of the acute phase response, accompanied by systemic lipid changes. Lipoproteins and their components, as well as lipid transport molecules, are emerging as novel actors in innate immune defence.

Key Concepts:

Macrophages interact with cells and organs involved in lipid uptake, distribution and storage.

The immune repertoire of macrophages and other immune cells includes a range of surface and intracellular lipid sensors that detect self and nonself lipids.

Phagocytosis of pathogens and apoptotic cells is modulated by lipid ligands.

The oxidative burst accompanying the immune response oxidises lipids and generates secondary messengers.

The intracellular cholesterol content of macrophages is sensed by the endoplasmic reticulum and by lipid‐binding nuclear receptors.

Lipid‐activated nuclear receptors including PPARs and LXRs adjust the transcriptome of macrophages and can modulate proinflammatory transcription factors such as NFκB.

Systemic or chronic immune activation is accompanied by secretory changes in the liver, a process called acute phase response.

Acute phase response proteins contribute to lipid scavenging in the circulation.

Apolipoproteins, transport molecules that carry lipids through the circulation, show a versatile antimicrobial, anti‐inflammatory and antitumour potential for therapy.
AMP
‐activated Protein Kinase (
AMPK
)
Authors: Hardie D Grahame
Published: July 2014

AMP‐activated protein kinase (AMPK) is a heterotrimeric protein kinase complex that is expressed in essentially all eukaryotes. It acts as a sensor of cellular energy status by monitoring the levels of adenine nucleotides, especially
adenosine‐5′‐monophosphate (AMP)
,
adenosine‐5′‐diphosphate (ADP)
and
adenosine‐5′‐triphosphate (ATP)
. When activated by falling cellular energy status, AMPK acts to restore energy balance by switching on ATP‐producing catabolic pathways (such as the uptake and oxidation of glucose and fatty acids), while switching off any energy‐requiring processes (such as biosynthesis, cell growth and division) that are not essential for short‐term cell survival. AMPK is also regulated by hormones and cytokines that control energy balance at the whole body level, and it is involved in several common disorders in humans, including type 2 diabetes and cancer.

Key Concepts:

An analogy can be drawn between cellular ATP and ADP and the chemicals in a rechargeable battery.

Catabolism (and/or photosynthesis) ‘charges the cellular battery’ by converting ADP to ATP.

Almost all other cellular processes require energy and are driven by conversion of ATP to ADP, thus ‘flattening the battery’.

All living cells must maintain a balance between ATP production and ATP consumption at all times, thus maintaining energy homoeostasis.

In eukaryotic cells, one key system that maintains energy homoeostasis is the AMP‐activated protein kinase (AMPK).

The gamma subunit of AMPK binds AMP, ADP and ATP, and increases in AMP:ATP and ADP:ATP ratios (signals of compromised cellular energy status) activate AMPK.

Once activated, AMPK switches on alternate catabolic pathways that generate ATP, while switching off energy‐consuming processes, thus conserving ATP.

Although it appears to have evolved to maintain energy homoeostasis in a cell‐autonomous manner, in multicellular eukaryotes AMPK is also regulated by hormones and cytokines that regulate whole body energy balance.

AMPK is a key drug target in the treatment of common human disorders such as type 2 diabetes, cancer and inflammatory disorders.
Biomolecular
NMR
Spectroscopy of Ribonucleic Acids
Authors: Dieckmann Thorsten , Piazza Michael , Bonneau Eric , Legault Pascale
Published: July 2014

Biomolecular nuclear magnetic resonance (NMR) spectroscopy allows the characterisation of structural and dynamic properties of
ribonucleic acids (RNAs)
in solution. The NMR‐based determination of high‐resolution three‐dimensional (3D) structures by NMR spectroscopy in solution is especially useful for small‐to‐medium sized RNA molecules like aptamers and small ribozymes, but has also been achieved for RNAs up to about 100 nucleotides in total size. Biomolecular NMR also provides valuable information about the interaction between RNA and diverse binding partners such as drugs, peptides, proteins or other nucleic acids. In addition, novel methods can be utilised to characterise the role of metal ions, intramolecular dynamics across a range of motion time scales and shifted p
K
a
values of exchangeable nucleobase protons in RNA structure and catalysis.

Key Concepts:

High‐resolution NMR spectroscopy in solution is a powerful method to determine the 3D structures of small and medium sized RNA molecule.

The structure determination of larger RNAs generally requires labelling with stable isotopes

The information about molecular dynamics that can be obtained by NMR experiments allows quantitative studies of molecular motion across a wide range of time scales.

The possibility to directly observe changes in the
pK

a

values of ionisable groups.

The localisation of divalent metal ions can be defined using several NMR methods.
Molecular Genetics of Paget's Disease of Bone
Authors: Gennari Luigi , Gianfrancesco Fernando , Rendina Domenico , Merlotti Daniela
Published: July 2014

Paget's disease of bone (PDB) is a chronic disorder of bone metabolism, which typically results in enlarged and deformed bones in one or more regions of the skeleton. The aetiology of PDB has remained unknown for several decades, but either environmental or genetic factors have been implicated. The former mainly concern the presence of a slow‐acting viral infection, a condition that may be present for many years before symptoms appear. However, there are also several data supporting a hereditary hypothesis, since in up to 40% of patients the disease may appear in more than one family member. The genetic architecture of PDB is incompletely understood, but recent evidence suggests that the disease may be caused by a combination of rare variants in genes such as
SQSTM
1 (detected in up to 50% of familial cases of PDB) and more common variants (i.e. polymorphisms) in genes such as
CSF1
,
TNFRSF11A
,
OPTN
and
TM7SF4
.

Key Concepts:

Paget's disease of bone (PDB) is a focal disorder of bone metabolism characterised by enlarged and deformed bones in one (monostotic form) or more regions (polyostotic form) of the skeleton.

Over the last two decades there have been major advances in our understanding of the genetic basis of the disorder. Mutations in 3 genes have been detected in rare syndromes related to PDB and mutations in
SQSTM1
gene have been associated with the classical form of PDB in up to 50% of familial cases.

SQSTM1
gene encodes for the p62/sequestosome 1 protein, which acts as a scaffold protein in the NFκB pathway as well as an intermediate protein in the proteosomal degradation of polyubiquitinated proteins.

To date the exact molecular mechanisms leading to the development of pagetic lesions in
SQSTM1
mutation carriers remain to be defined. Indeed, recent experimental evidence suggests that additional contribution from environmental factors (i.e. a viral infection with paramyxovirus) or other genetic factors (i.e. polymorphisms) may be required to induce the full pagetic phenotype in the presence of
SQSTM1
mutation.

The genetic cause of PDB in familial cases negative for
SQSTM1
mutations remains to be determined in more detail.
The Molecular Genetics of Corticotroph Tumours
Authors: Dworakowska Dorota , Grossman Ashley B
Published: July 2014

Cushing disease caused by adrenocorticotropin ‐secreting pituitary adenomas leads to hypercortisolaemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity and increased mortality. Previous studies have enhanced our knowledge on the genetic basis of familial pituitary adenomas, including the McCune–Albright syndrome, multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), Carney complex, the MEN1‐like phenotype (MEN4), pituitary adenoma predisposition syndromes and tuberous sclerosis. These studies, however, have done little to elucidate the causes of sporadic pituitary tumours, including Cushing disease.

We summarise the information available on the molecular derangements of corticotroph tumours, including the most recent advances in the molecular genetics of sporadic lesions, which were published after the latest review on this topic written in 2011. We have left for further reading information about silent corticotroph adenomas, as well as plurihormonal expressing adenomas. We also suggest that more general literature for the readers who want to broaden their knowledge on the molecular biology in general of pituitary adrenomas.

Key Concepts:

Some 5% of pituitary adenomas are familial.

Previous studies have enhanced our knowledge on the genetic basis of familial pituitary adenomas including the McCune–Albright syndrome (MAS), multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), Carney complex (CNC), the MEN1‐like phenotype (MEN4), pituitary adenoma predisposition (PAP) syndromes and tuberous sclerosis (TSC).

These studies, however, have done little to elucidate the causes of sporadic pituitary tumours, including Cushing disease.

Molecular studies on pituitary tumours have shown that alterations in the best known tumour suppressor genes in other neoplasms (e.g.
P53
,
RB
, etc.) or common oncogenes (e.g. the
Ras
‐familly) are only rarely involved in the development of these tumours.

Silent corticotroph adenomas (SCA) are rare pituitary tumours that are immunoreactive for ACTH, but without clinical evidence of Cushing disease, and tend to show aggressive features.

Future work should focus on understanding the molecular mechanisms that control pituitary tumour transformation, where intracellular signalling molecules will constitute not only diagnostic/prognostic markers but also novel therapeutic targets.
Adaptive Evolution in Passerine Birds
Authors: Backström Niclas
Published: July 2014

Adaptive evolution is the process whereby mutations that provide the carrier with a selective advantage increase in frequency in a population via the process of natural selection. Passerines are widespread, common and long‐term targets for field study and they demonstrate a copious diversity in physiological and morphological adaptations to varying habitats, for example, beak size and wing shape, and they are, therefore, an important study system to understand adaptive evolution. Recent technological advancements have made it easier to investigate the mechanistic and evolutionary underpinnings of adaptive evolution by allowing genome sequence data to be generated in almost any species of interest. However, it is important to assess the contribution of neutral forces like demographic events and GC‐biased gene conversion before concluding that selection has shaped the patterns observed in genomic data. Initial analyses in passerines have identified candidate genes that might be involved in, for example, song learning, beak morphology, disease resistance, high‐altitude adaptation and exploratory behavior, but functional verifications are needed to establish a causative relationship between the identified genes and the traits.

Key Concepts:

Passerines are widespread, generally common and easy targets for field study and they demonstrate a copious diversity in physiological and morphological adaptations to varying habitats and they have, therefore, played an important role in previous studies concerning behaviour, ecology and evolution.

A full understanding of passerine adaptations requires an integrative approach aiming at identifying and characterising both proximate (mechanistic) and ultimate (evolutionary) underpinnings to adaptive traits.

The recent advancements in molecular techniques allows for using both comparative genomics, expression profiling, candidate gene approaches and classical association and QTL mapping strategies to identify the genetic basis of adaptive traits in passerines.

Groundwork studies of ecological genetics and genomics using comparative approaches, expression profiling and candidate genes are now accumulating and in a handful of cases we have an idea about the genetic basis of adaptive traits related to, for example, dietary specialisation, learning, exploratory behaviour, immune response and high‐altitude adaptations in passerines.

Demographic history and other neutral processes, for example, GC‐biased gene conversion (gcBGC), may mimic signals of selection and it is important to verify findings of adaptive evolution using independent methods.
Water‐Induced Phase Separation Forming Macrostructured Epitaxial Quartz Films on Silicon
Authors: Drisko Glenna L. , Carretero‐Genevrier Adrian , Gich Martí , Gàzquez Jaume , Ferrah Djawhar , Grosso David , Boissière Cédric , Rodriguez‐Carvajal Juan , Sanchez Clément
Published: July 2014

Quartz has been widely used as a bulk material in optics, the microelectronic industry, and sensors. The nanostructuring and direct integration of oriented quartz crystals onto a semiconductor platform has proven to be challenging. However, here, a new approach is presented to integrate epitaxial quartz films with macroperforations within the range of 500 nm and 1 μm using chemical solution deposition. This method constitutes an appealing approach to develop piezoelectric mass sensors with enhanced resonance frequencies due to the thickness reduction. Perforated quartz films on (100)‐silicon are prepared from amorphous silica films deposited via dip‐coating and doped with metal cations that catalyze quartz crystallization. The metal cations are also active in the formation of the macroperforations, which arise due to a phase separation mechanism. Cationic surfactant–anion–metal cation assemblies stabilize droplets of water, creating an indentation in the hydrophilic silica matrix which remains after solvent evaporation. Many cations induce phase separation, including Li+, Na+, Sr2+, Mn2+, Fe2+/Fe3+, Ca2+, Ce3+ and La3+ but only the Sr2+ and Ca2+ cations in this series induce the epitaxial growth of α‐quartz films under the conditions studied. The combination of sol–gel chemistry and epitaxial growth opens new opportunities for the integration of patterned quartz on silicon.
Solution‐Processable Hosts Constructed by Carbazole/PO Substituted Tetraphenylsilanes for Efficient Blue Electrophosphorescent Devices
Authors: Liu He , Bai Qing , Yao Liang , Hu Dehua , Tang Xiangyang , Shen Fangzhong , Zhang Huanhuan , Gao Yu , Lu Ping , Yang Bing , Ma Yuguang
Published: July 2014

Two new solution‐processable wide bandgap materials, bis(4‐((4‐(9‐H‐carbazol‐9‐yl)phenyl)diphenylsilyl)phenyl)(phenyl)phosphine oxide (CS2PO) and bis(4‐((4‐(9‐H‐(3,9′‐bicarbazol)‐9‐yl)phenyl)diphenylsilyl)phenyl)(phenyl)phosphine oxide (DCS2PO), have been developed for blue phosphorescent light‐emitting diodes by coupling an electron‐donating carbazole moiety and an electron‐accepting PO unit together via double‐silicon bridges. Both of them have been characterized as having high glass transition temperatures of 159–199 °C, good solubility in common organic solvent (20 mg mL−1), wide optical gap (3.37–3.55 eV) and high triplet energy levels (2.97–3.04 eV). As compared with their corresponding single‐silicon bridged compounds, this design strategy of extending molecular structure endows CS2PO and DCS2PO with higher thermal stability, better solution processability and more stable film morphology without lowering their triplet energies. As a result, DCS2PO/FIrpic doped blue phosphorescent device fabricated by spin‐coating method shows the best electroluminescent performance with a maximum current efficiency of 26.5 cd A−1, a maximum power efficiency of 8.66 lm W−1, and a maximum external quantum efficiency of 13.6%, which is one of the highest efficiencies among small molecular devices with the same deposition process and device configuration.
Effect of phenol end functional switching segments on the shape memory properties of epoxy‐cyanate ester system
Authors: Biju R. , Nair C. P. Reghunadhan
Published: July 2014

The effect of phenol end functional shape memory oligomers on the shape memory properties of an epoxy‐cyanate ester resin system was examined. The basic resin system consisted of diglycidyl ether of bisphenol A (DGEBA) cured with bisphenol A dicyanate (BADC). For conferring the shape memory properties, the switching segment (SS) components selected are α, ω‐phenol‐terminated poly(tetramethyleneoxide) (PPTMO), poly(ε‐caprolactone) (PPCL), and poly(propylene glycol) (PPPG). Epoxy‐cyanate ester blend of defined composition was analyzed for thermal, mechanical, thermo‐mechanical, and shape memory properties at two concentrations of the three SSs. The transition temperature of heavily SS loaded matrix increased in the order: PPTMO < PPCL < PPPG commensurate with crystallizability of SS segments at ambient. For same reason flexural property showed an increasing trend. This is in league with the increased crystallizability of the shape memory polymer components. The shape fixity, recovery extent, and recovery time followed a reverse order: PPPG < PPCL < PPTMO. In contrast to the alcohol terminated shape memory components, phenol terminal groups were helpful in integrating the shape memory segments into the matrix by way of reaction with both epoxy and cyanate groups. The coreaction was conducive for achieving better shape memory properties and decreasing the transition temperature. A direct relation existed between the modulus ratio and the shape recovery property. Higher concentration of the SSs caused a diminution in transition temperature but enhanced the shape memory properties, though the mechanical properties were adversely affected. The shape recovery increased with increase in temperature. All polymers possessed good mechanical properties and thermal stability. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41196.
Recognition of the DNA Minor Groove by Thiazotropsin Analogues
Authors: Alniss Hasan Y. , Salvia Marie‐Virginie , Sadikov Mykhailo , Golovchenko Igor , Anthony Nahoum G. , Khalaf Abedawn I. , MacKay Simon P. , Suckling Colin J. , Parkinson John A.
Published: July 2014

Solution‐phase self‐association characteristics and DNA molecular‐recognition properties are reported for three close analogues of minor‐groove‐binding ligands from the thiazotropsin class of lexitropsin molecules; they incorporate isopropyl thiazole as a lipophilic building block. Thiazotropsin B (AcImPyiPrThDp) shows similar self‐assembly characteristics to thiazotropsin A (FoPyPyiPrThDp), although it is engineered, by incorporation of imidazole in place of N‐methyl pyrrole, to swap its DNA recognition target from 5′‐ACTAGT‐3′ to 5′‐ACGCGT‐3′. Replacement of the formamide head group in thiazotropsin A by nicotinamide in AIK‐18/51 results in a measureable difference in solution‐phase self‐assembly character and substantially enhanced DNA association characteristics. The structures and associated thermodynamic parameters of self‐assembled ligand aggregates and their complexes with their respective DNA targets are considered in the context of cluster targeting of DNA by minor‐groove complexes.
Risk prediction of hepatocellular carcinoma in patients with cirrhosis: The ADRESS‐HCC risk model
Authors: Flemming Jennifer A. , Yang Ju Dong , Vittinghoff Eric , Kim W. Ray , Terrault Norah A.
Published: July 2014

BACKGROUND

All patients with cirrhosis are at risk of developing hepatocellular carcinoma (HCC). This risk is not uniform because other patient‐related factors influence the risk of HCC. The objective of the current study was to develop an HCC risk prediction model to estimate the 1‐year probability of HCC to assist with patient counseling.

METHODS

Between 2002 and 2011, a cohort of 34,932 patients with cirrhosis was identified from a national liver transplantation waitlist database from the United States. Cox proportional hazards regression methods were used to develop and validate a risk prediction model for incident HCC. In the validation cohort, discrimination and calibration of the model was examined. External validation was conducted using patients with cirrhosis who were enrolled in the Hepatitis C Antiviral Long‐term Treatment against Cirrhosis (HALT‐C) study.

RESULTS

HCC developed in 1960 patients (5.6%) during a median follow‐up of 1.3 years (interquartile range, 0.47 years‐2.83 years). Six baseline clinical variables, including age, diabetes, race, etiology of cirrhosis, sex, and severity (ADRESS) of liver dysfunction were independently associated with HCC and were used to develop the ADRESS‐HCC risk model. C‐indices in the derivation and internal validation cohorts were 0.704 and 0.691, respectively. In the validation cohort, the predicted cumulative incidence of HCC by the ADRESS‐HCC model closely matched the observed data. In patients with cirrhosis in the HALT‐C cohort, the model stratified patients correctly according to the risk of developing HCC within 5 years.

CONCLUSIONS

The ADRESS‐HCC risk model is a useful tool for predicting the 1‐year risk of HCC among patients with cirrhosis. Cancer 2014;120:3485–3493. © 2014 American Cancer Society.
Effect of Urea on the Morphology of Co3O4 Nanostructures and Their Application for Potentiometric Glucose Biosensor
Authors: Ibupoto Zafar Hussain , Elhag Sami , AlSalhi M. S. , Nur Omer , Willander Magnus
Published: July 2014

In this study, an effect of different concentrations of urea on the morphology of cobalt oxide (Co3O4) nanostructures was investigated. The Co3O4 nanostructures are fabricated on gold coated glass substrate by the hydrothermal method. The morphological and structural characterization was performed by scanning electron microscopy, and X‐ray diffraction techniques. The Co3O4 nanostructures exhibit morphology of flowers‐like and have comprised on nanowires due to the increasing amount of urea. The nanostructures were highly dense on the substrate and possess a good crystalline quality. The Co3O4 nanostructures were successfully used for the development of a sensitive glucose biosensor. The presented glucose biosensor detected a wide range of glucose concentrations from 1×10−6 M to 1×10−2 M with sensitivity of a −56.85 mV/decade and indicated a fast response time of less than 10 s. This performance could be attributed to the heterogeneous catalysis effect at glucose oxidase enzyme, nanoflowers, and nanowires interfaces, which have enhanced the electron transfer process on the electrode surface. Moreover, the reproducibility, repeatability, stability and selectivity were also investigated. All the obtained results indicate the potential use of the developed glucose sensor for monitoring of glucose concentrations at drugs, human serum and food industry related samples.
Gene alterations involving the CRLF2‐JAK pathway and recurrent gene deletions in Down syndrome‐associated acute lymphoblastic leukemia in Japan
Authors: Hanada Isamu , Terui Kiminori , Ikeda Fumika , Toki Tsutomu , Kanezaki Rika , Sato Tomohiko , Kamio Takuya , Kudo Ko , Sasaki Shinya , Takahashi Yoshihiro , Hayashi Yasuhide , Inukai Takeshi , Kojima Seiji , Koike Kenichi , Kosaka Yoshiyuki , Kobayashi Masao , Imaizumi Masue , Mitsui Tetsuo , Hori Hiroki , Hara Junichi , Horibe Keizo , Nagai Jun‐ichi , Goto Hiroaki , Ito Etsuro
Published: July 2014

In Western countries, gene alterations involving the CRLF2‐JAK signaling pathway are identified in approximately 50–60% of patients with Down syndrome‐associated acute lymphoblastic leukemia (DS‐ALL), and this pathway is considered a potential therapeutic target. The frequency of BTG1 deletions in DS‐ALL is controversial. IKZF1 deletions, found in 20–30% of DS‐ALL patients, are associated with a poor outcome and EBF1 deletions are very rare (∼2%). We analyzed 38 patients to determine the frequencies and clinical implications of CRLF2‐JAK pathway genetic alterations and recurrent gene deletions in Japanese DS‐ALL patients. We confirmed a high incidence of P2RY8‐CRLF2 (29%) and JAK2 mutations (16%), though the frequency of P2RY8‐CRLF2 was slightly lower than that in Western countries (∼50%). BTG1 deletions were common in our cohort (25%). IKZF1 deletions were detected in 25% of patients and associated with shorter overall survival (OS). EBF1 deletions were found at an unexpectedly high frequency (16%), and at a significantly higher level in P2RY8‐CRLF2‐positive patients than in P2RY8‐CRLF2‐negative patients (44% vs. 4%, P = 0.015). Deletions of CDKN2A/B and PAX5 were common in P2RY8‐CRLF2‐negative patients (48 and 39%, respectively) but not in P2RY8‐CRLF2‐positive patients (11% each). Associations between these genetic alterations and clinical characteristics were not observed except for inferior OS in patients with IKZF1 deletions. These results suggest that differences exist between the genetic profiles of DS‐ALL patients in Japan and in Western countries, and that P2RY8‐CRLF2 and EBF1 deletions may cooperate in leukemogenesis in a subset of Japanese DS‐ALL patients. © 2014 Wiley Periodicals, Inc.
Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation‐induced cognitive damage
Authors: Fishbein‐Kaminietsky Miriam , Gafni Mikhal , Sarne Yosef
Published: July 2014

In our previous studies, we found that a single ultralow dose of tetrahydrocannabinol (THC; 0.002 mg/kg, three to four orders of magnitude lower than the conventional doses) protects the brain from different insults that cause cognitive deficits. Because various insults may trigger a neuroinflammatory response that leads to secondary damage to the brain, the current study tested whether this extremely low dose of THC could protect the brain from inflammation‐induced cognitive deficits. Mice received a single injection of THC (0.002 mg/kg) 48 hr before or 1–7 days after treatment with lipopolysccharide (LPS; 10 mg/kg) and were examined with the object recognition test 3 weeks later. LPS caused long‐lasting cognitive deficits, whereas the application of THC before or after LPS protected the mice from this LPS‐induced damage. The protective effect of THC was blocked by the cannabinoid (CB) 1 receptor antagonist SR14176A but not by the CB2 receptor antagonist SR141528 and was mimicked by the CB1 agonist ACEA but not by the CB2 agonist HU308. The protective effect of THC was also blocked by pretreatment with GW9662, indicating the involvement of peroxisome proliferator‐activated receptor‐γ. Biochemical examination of the brain revealed a long‐term (at least 7 weeks) elevation of the prostaglandin‐producing enzyme cyclooxygenase‐2 in the hippocampus and in the frontal cortex following the injection of LPS. Pretreatment with the extremely low dose of THC tended to attenuate this elevation. Our results suggest that an ultralow dose of THC that lacks any psychotrophic activity protects the brain from neuroinflammation‐induced cognitive damage and might be used as an effective drug for the treatment of neuroinflammatory conditions, including neurodegenerative diseases. © 2014 Wiley Periodicals, Inc.