bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semliki Forest Virus
Expression System
Authors: Sjöberg Mathilda 
Published: July 2014

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractAdaptive 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.
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

ABSTRACTThe 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

AbstractSolution‐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

BACKGROUNDAll 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.METHODSBetween 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.RESULTSHCC 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.CONCLUSIONSThe 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.