bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Exome Sequencing to Mendelian Disorders and the Emergence of Personalised Medicine
Authors: Raszek Mikolaj M
Published: September 2013

Since the introduction of next‐generation sequencing, the field of genomic medicine has expanded rapidly. Whole‐exome sequencing (WES) can sequence thousands of functional genes at a time and has become the tool of choice for the discovery of causative genetic variants, especially for Mendelian diseases. This approach also expands the knowledge of novel mutations of established genes linked to a particular disease, and helps to uncover the complex interplay between modifier variants that contribute to a disease phenotype. For these reasons, WES can perform diagnoses that would be difficult to accomplish with traditional methods, particularly for diseases that exhibit a broad genetic or phenotypic heterogeneity. Together, these trends already have begun to influence the quality of patient care and appear to fulfil the promise of personal medicine. The article summarises recent literature that highlights these trends, and discusses the limitations and ethical considerations surrounding this new technology.

Key Concepts:

Next‐generation sequencing is driving the emergence of personalised medicine.

Superiority of WES as a diagnostic tool over traditional genetic methods is apparent, especially for diseases that are genetically and phenotypically heterogenous.

WES utility is a rapidly expanding field of genetic aetiology.

The underlying genetic complexity of monogenic diseases might have been underappreciated.

The clinical manifestation of monogenic diseases is driven by a complex interplay of a multitude of genetic modifiers.

The incidentalome remains an important ethical issue, but important steps forward have been taken with the work of Dr. Berg and collaborators commencing in 2011.

The rapidly expanding field of genomics faces important technical limitations: storage space and analysis capability.

Important ethical questions need to be addressed with regard to the use of NGS technology; this includes rights to data access and issues regarding follow‐up data reanalysis.
Stazione Zoologica Anton Dohrn
Authors: Groeben Christiane
Published: September 2013

TheStazione Zoologica di Napoli(SZN) was founded in 1872 by the German zoologist Anton Dohrn as an independent and international research institute for marine biology. Owing to Dohrn's vision and managerial skill the Naples Station was soon considered the Mecca of zoologists. Darwin defined it ‘a great service’ to Science. The administrative and scientific internationality was based on the table system, that is, the renting out of lab space. With World War I the station ceased to be the private property of Dohrn's son and successor Reinhard. In 1923, the SZN was changed into an Italian semiprivate institution (Ente Morale); in 1982 it became a National Research Institute under the supervision of the Italian Ministry of Instruction, University and Research (MIUR). Its scientific policy changed during the 1990s from guest research to in‐house research programmes, still focussed on interdisciplinary and international research.

Key Concepts:

Research institutions are organisms of their own right.

The balance between vision and management allows for a sustainable mission.

Research institutes are political structures.

The Naples Station has maintained its scientific autonomy due to the sustainable vision of its founder.

Hospitality at the scientific, theoretical and social level is a key factor to keep an institute alive and competitive.

Networking and sharing resources is essential for marine stations.
Congruence of Cranial and Genetic Estimates of Old World Primate Phylogeny
Authors: von Cramon‐Taubadel Noreen
Published: September 2013

Inferring the phylogenetic relationships amongst fossil hominins is necessarily based on morphological data. Attempts to reconstruct fossil hominin phylogeny have yielded inconsistent and inconclusive results. Old world primates – apes and old world monkeys – provide key referents for understanding the phylogenetic signal in cranial data. Application of phylogenetic methods to cranial data from primate taxa has failed to uncover the known molecular genetic relationships of these major primate groups, suggesting that hominin phylogeny based on morphological data cannot be estimated with complete accuracy. Propositions regarding the potential efficacy of individual cranial regions have been empirically tested in both apes and old world monkeys. No clear criteria have been uncovered to predict the potential efficacy of cranial regions. However, recent studies have suggested that the taxonomic scale of the analysis and the allometric scaling relationships amongst taxa may both play key roles in determining the phylogenetic efficacy of cranial data.

Key Concepts:

Palaeoanthropologists rely on fossilised cranial remains to infer evolutionary history of hominins.

Extant primates form necessary inference models for understanding human evolution.

Attempts to reconstruct hominin phylogenies have generated inconsistent results.

Some cranial traits are likely to be more reliable for reconstructing phylogeny than others.

Masticatory traits have higher within‐taxon variance than nonmasticatory traits, but do not have lower phylogenetic efficacy.

Basicranial traits may have higher phylogenetic efficacy in some primate groups.

No clear rules exist for deciding which cranial traits have the greatest potential to uncover hominin relationships.

Allometric scaling relationships among taxa affect the inference of phylogenetic relatedness.

Taxonomic scale at which cranial–genetic congruence analyses are conducted may also be important.
Evolution of Hominin Social Systems
Authors: Grove Matt
Published: September 2013

This article summarises research into the evolution of hominin social systems arising from the studies of archaeological materials, hunter–gatherer ethnography and primatological studies. The history of models in archaeology is briefly summarised, and it is noted that there has been a gradual shift from ethnographically based models to those admitting a combination of hunter–gatherer and primate analogies. Where prehistoric group sizes have been estimated from anatomical and archaeological data, these suggest trajectories of increasing group size through time. The fission–fusion or multilevel societies of extant hunter–gatherers show clear parallels to those of some primates, suggesting both ecological and sociocognitive constraints on social structures. Mating systems can be reconstructed via measurements of skeletal and dental dimorphism, though these necessarily reflect social aspects of intersexual contact rather than patterns of genetic reproduction. Finally, contemporary readings of the archaeological record suggest that the evolution of hominin social systems can be viewed as a gradual stretching of the scale of social life.

Key Concepts:

Early archaeological models of hominin social systems were based on simple hunter–gatherer analogies.

Observed commonalities between primate and human societies have led to a wealth of new research.

Prehistoric group sizes can be estimated via both anatomical and archaeological proxies.

Group sizes show an exponential increase through the course of the Palaeolithic.

Hominins developed multilevel societies which paralleled those of chimpanzees in some aspects and baboons in others.

Sexual dimorphism in hominin fossils can be used to reconstruct mating systems.

The evolution of hominin social systems is characterised by a gradual increase in the spatial scale of social life.
Mammalian Sex Determination
Authors: Tucker Elena J , Sinclair Andrew H
Published: September 2013

Mammals, birds, reptiles, insects and even some corals all have two distinct forms – male and female. Cues for sexual development have undergone rapid evolution with some species relying on genetic cues and others on environmental. In mammals, sex development is governed by genetics and almost always involves heterogametic XY males and homogametic XX females. The Y chromosome contains a sex‐determining gene that initiates a cascade of developmental signals down the male path, leading to the development of testes and subsequently the male‐specific sex cords and genitalia. In the absence of the Y chromosome, development proceeds down the female path leading to ovaries and female genitalia. Mammalian sex determination involves a complex interplay of many genes, with antagonism between male and female pathways reinforcing fate. Despite the finely tuned process of sex determination, genetic aberrations can tip the balance, leading to sex reversal or intermediate sex development. Humans and mice with disruptions in key gonadal genes leading to atypical sex development have provided the majority of insights into the process of sex development, but much remains to be learned.

Key Concepts:

Mammals are sexually dimorphic.

Sex development has undergone rapid evolution.

Mammalian sex development is governed by complex genetic networks.

Study of humans and mice with atypical sex development have provided insights into the genetic pathways of sex development.

Massively parallel sequencing will accelerate future discoveries into the genetic basis of sex development.
Genetics of Graves' Disease
Authors: Hamilton Alexander , Gough Stephen CL , Simmonds Matthew J
Published: September 2013

Graves' disease (GD) is a common autoimmune condition characterised by autoantibody attack against components of the thyroid gland which leads to hyperthyroidism. Both genetic and environmental factors have been implicated in disease onset. Uncovering the genetic contribution to GD has revealed that the disease is caused by a variety of factors encompassing both immunological and thyroid specific pathways. Recent advancements in genetic screening technologies, including the success of genome‐wide association studies, have provided further insights into GD susceptibility loci. The challenge now is to determine how these newly found susceptibility loci play a role in disease while simultaneously identifying the remainder of the genetic contribution to GD. This will, in turn, piece together the complex pathogenic pathways associated with GD, painting a clearer picture of disease development and with it the provision of new opportunities for improved therapeutics and treatment strategies.

Key Concepts:

In Graves' disease (GD) autoantibodies are produced which bind to and constitutively activate the thyroid‐stimulating hormone receptor usually resulting in the overproduction of the thyroid hormones, triiodothyronine and thryoxine.

GD is a complex disease caused by a variety of genetic and environmental factors.

A variety of different genetic approaches have been used to detect the genetic contribution to GD, including case‐control studies and genome‐wide association scans.

GD susceptibility loci are likely to alter both immunological and thyroid specific pathways.

Many of the GD susceptibility loci are also found to contribute to other autoimmune diseases suggesting the presence of shared autoimmune disease pathways.

Confirmed GD susceptible loci, detected to date, only account for a small amount of the observed genetic effect, with a large degree of genetic heritability still unaccounted for.

Fine mapping of known gene effects, screening of low frequency and rare variants and investigating gene–gene and gene–environment interactions are currently being undertaken to locate the remaining missing genetic heritability for GD.
RNA‐Seq and Human Complex Disease
Authors: Ciccodicola Alfredo , Aversa Rosanna , Esposito Roberta , Costa Valerio
Published: September 2013

The Human Genome Project and next‐generation sequencing technologies contributed to identify disease‐causing mutations in Mendelian disorders and susceptibility loci in complex disease. Despite the progresses, studying multifactorial diseases still remains a challenge. Most of the genome‐wide association studies have not explained the causative role of nucleotide variations in complex diseases, and several polymorphisms so far identified have been shown to affect gene expression and alternative splicing. It has highlighted the importance of studying the transcriptome in the context of these diseases.

Ribonucleic acid (RNA)
‐sequencing is providing an unprecedented opportunity to quantify in a single experiment – other than gene expression levels – the extent of alternative splicing and allele‐specific expression, as well as to identify novel genes, splice isoforms, chimaeric transcripts, and to investigate noncoding RNAs.

Here, the authors describe the advantages of using RNA‐Seq to study human complex diseases, paying attention to metabolic–cardiovascular disorders, neurodegenerative and neuropsychiatric diseases, and cancer.

Key Concepts:

Complex diseases are caused by intricate molecular interactions, involving both genetic and environmental factors. Their aetiology remains mostly unknown.

The causative role of single‐nucleotide polymorphisms and of other DNA variations to complex disease susceptibility has not yet been provided.

Most of GWAS‐associated SNPs fall in regulatory regions and directly affect gene expression levels and alternative splicing.

Transcriptome analysis is emerging as a promising approach to understand the impact of nucleotide variations on gene expression levels and splicing in the diseases' aetiology.

RNA‐Seq allows the precise quantification of expression levels of known genes, the identification of novel coding and noncoding transcripts as well as alternative splice isoforms and chimeric transcripts.

RNA‐Seq – based on high‐throughput sequencing – overcomes many microarray's drawbacks and represents a promising tool for transcriptomic studies.

Whole‐transcriptome analysis by RNA‐Seq is revealing a powerful approach to study complex diseases.
Molecular Genetics of Hypobetalipoproteinaemia and Abetalipoproteinaemia
Authors: Hooper Amanda J , Burnett John R
Published: September 2013

Genetic disorders of lipoprotein metabolism can cause marked hypocholesterolaemia with low or absent low‐density lipoprotein (LDL) cholesterol and apolipoprotein B (apoB) concentrations in plasma, depending on the gene involved and mode of inheritance of the condition, together with the severity of the mutation or mutations present. Hypobetalipoproteinaemia is defined as a plasma LDL cholesterol and apoB less than the 5th centile for age and sex, and when mutations in theAPOBgene are inherited in a codominant fashion is known as familial hypobetalipoproteinaemia (FHBL). Abetalipoproteinaemia, which is clinically indistinguishable from homozygous FHBL, is a very rare recessive disorder caused by mutations inMTTPand characterised by the absence of apoB‐containing lipoproteins in the plasma. Loss‐of‐function mutations inPCSK9, particularly nonsense mutations, are also associated with hypobetalipoproteinaemia, but lack any clinical features. More recently, mutations inANGPTL3were found to cause recessive familial combined hypolipidaemia, characterised by a reduction in all plasma lipids.

Key Concepts:

Hypobetalipoproteinaemia is defined as low levels (<5th centile) of plasma LDL cholesterol and apolipoprotein B, whereas in abetalipoproteinaemia these analytes may be undetectable.

Heterozygous FHBL is generally caused by truncations in apoB, and is associated with hepatic steatosis and a low risk of cardiovascular disease.

Homozygous FHBL and abetalipoproteinaemia result in a variable clinical phenotype and are caused by mutations inAPOBandMTTP, respectively.

Loss‐of‐function mutations inPCSK9are associated with low plasma LDL cholesterol concentrations and low risk of cardiovascular disease, and no clinical phenotype.

ANGPTL3mutations cause familial combined hypolipidaemia, a newly described recessive condition characterised by reductions in all plasma lipids.
Role of Autophagy‐Related Genes in the Pathology of Inflammatory Bowel Disease
Authors: Tian Chaorui , Kabi Amrita , McDonald Christine
Published: September 2013

Inflammatory bowel disease (IBD) is a complex, multifactorial disease with genetic, microbial and environmental risk factors combining to result in recurrent inflammation of the intestine. Genetic analyses have uncovered a cluster of IBD risk genes, which regulate a cell stress response called autophagy. Functional studies of these autophagy‐related genes highlight contributions of disease‐associated dysregulation to several aspects of IBD pathology, which include alterations in microbiome composition and bacterial responses (xenophagy), antimicrobial peptide production by Paneth cells (crinophagy), enhanced levels of proinflammatory cytokines and enhanced T‐cell subset responses. This suite of autophagy‐gene regulated responses is modulated not only by the cell type or stimulus, but also by environmental context, with the overall balance of responses critical to the maintenance of health or induction of disease. These findings have opened up new avenues for the development of IBD therapeutics and increased understanding of disease mechanisms to facilitate a more personalised approach to the treatment of IBD.

Key Concepts:

Susceptibility to IBD disease is associated with genetic variants in a spectrum of autophagy‐related genes.

Autophagy is a tightly regulated catabolic degradative pathway implicated in a number of disease‐associated processes.

Autophagy‐dependent processes altered in IBD include intracellular bacterial killing by xenophagy, Paneth cell antimicrobial peptide secretion via crinophagy, production of proinflammatory cytokines by macrophages, antigen presentation and endoplasmic reticulum (ER) stress responses in enterocytes.

Xenophagy is impaired by IBD‐associated polymorphisms inATG16L1,IRGM,NOD2,RIP2,PTPN2andXBP1resulting in chronic inflammation due to defective clearance of intracellular pathogens.

Both impaired and enhanced crinophagy are observed in Paneth cells from IBD patients. Alterations in crinophagy supress secretion of antimicrobial peptides by these cells.

Proinflammatory cytokine production by macrophages is enhanced in IBD. This process is regulated by a balance between autophagy and inflammasome responses. Genetic variants in both pathways are associated with increased IBD susceptibility.

Defective autophagy in dendritic cells, through gene knockdown or carriage of disease risk alleles inATG16L1,IRGMorNOD2, alters antigen presentation and enhances T‐cell stimulation.

ER stress activates autophagy through stimulation of the unfolded protein response mediated by XBP1. Disease‐associated alleles ofXBP1are implicated in Paneth cell dysfunction and decreased xenophagy.
Mouse Genetic and Phenotypic Resources as Tools for Human Genetics
Authors: Hancock John M
Published: September 2013

The laboratory mouse community provides a rich set of data and material resources for scientists. The primary one is the Mouse Genome Informatics resource at the Jackson Laboratory (JL), supplemented by other resources at the JL and elsewhere, including a rich variety of gene expression information often presented in the form of gene expression atlases. Ordering and distribution of mutant and inbred mouse strains is well organised via the International Mouse Strain Resource. Resources such as knockout embryonic stem cells from the International Knockout Mouse Consortium (IKMC) and other nontraditional genetic resources such as the Collaborative Cross, Diversity Outbred and Chromosome Substitution lines are also available via the web. Systematic phenotyping of mouse strains, in particular knockout strains from the IKMC, is a new and developing field with a developing informatics infrastructure, which uses new approaches to data representation via ontologies to integrate data across species and to human disease information.

Key Concepts:

The laboratory mouse is the premier model organism for studying human disease.

There is a rich data infrastructure centred around the Mouse Genome Informatics project at the Jackson Laboratory.

Material resources (mouse strains, vector, etc) are also widely available to academic researchers, often at cost price.

The new systematic phenotyping projects being developed by the mouse community are developing new informatics infrastructure.

The development of new ontological approaches to representing phenotype data have opened up new opportunities to link mouse models to human disease.
Molecular Genetics of Barth Syndrome
Authors: Takeda Atsuhito
Published: September 2013

Barth syndrome (OMIM #
302060
) (BTHS) is an X‐linked disorder of lipid metabolism characterised by cardiomyopathy, skeletal myopathy, neutropaenia, growth delays and 3‐methylglutaconic aciduria. The causative mutations for BTHS are in the TAZ gene, which encode a putative acyltransferase named tafazzin, involved in the remodelling of cardiolipin (CL) in the inner mitochondrial membranes. To date, more than 120 different disease‐causing TAZ gene mutations have been reported. Mutations in the TAZ gene cause accumulation of monolysoCL and reduced levels of tetralinoeoyl CL, which result in mitochondrial structural and functional abnormalities. The functional role of CL has been investigated using model systems for BTHS such as yeast, zebrafish and flies. Recently, an inducible tafazzin knockdown mouse demonstrated abnormal fetal heart development with altered mitochondrial ultrastructure. Current understanding of the molecular genetics of BTHS including CL metabolism, mitochondrial disorders and clinical presentations are reviewed.

Key Concepts:

Barth syndrome is an X‐linked disorder of lipid metabolism characterised by cardiomyopathy, skeletal myopathy, neutropaenia, growth delays and 3‐methylglutaconic aciduria.

Barth syndrome is recognised as cardiolipin remodelling disorder due to the TAZ mutation.

TAZ gene encodes tafazzin protein, which has a central role in the reacylation of MLCL to L4‐CL in the mitochondria.

Cardiolipin plays a crucial role for both mitochondrial membrane structure and function.

The role of tafazzin and cardiolipin in the mitochondria remains to be elucidated.

Several model systems for Barth syndrome have been developed to elucidate the disease pathophysiology.

Mouse model of Barth syndrome provide new insight into the role of tafazzin.
Molecular Genetics of Primary Varicose Vein Disease
Authors: Adesina‐Georgiadis KN , Anwar MA , Davies AH
Published: September 2013

There is sufficient empirical evidence to suggest that there is a significant genetic contribution to the development of varicose vein (VV) disease. However, it is also clear that VV is a complex disease, which is ultimately determined by a number of genetic and environmental factors. The fact that VV are also a secondary manifestation of other vascular conditions further convolutes the understanding of the aetiology and the underlying molecular mechanisms. Despite there being many techniques which are routinely used to characterise the genetic factors involved, these strategies have inherent limitations. Furthermore, the elucidation of a factor's contribution is a complex process, due to the fact that any effect present may be confounded by other parallel effects. To fully understand the genetic contribution to VV disease, there is a need to formulate a rigorous research protocol which should utilise some of the very advanced genetic approaches.

Key Concepts:

Family history, age, sex and pregnancy are the established risk factors for varicose vein disease; however, not all individuals with these risk factors develop the disease.

Abnormal changes in varicose vein walls have been noticed independent of valve damage suggesting that primary vein wall damage is an epiphenomenon of the disease. However, the molecular mechanism behind the vein wall damage is poorly understood.

Empirical evidence suggests a strong genetic link to the disease; however, questionnaire‐based studies are subject to biases.

There are several approaches available to determine the genetic link. Genes expression profiling using microarray technique has been used in varicose veins but it does not explain whether the expressed genes are the cause or the effect of the disease. Candidate gene studies have shown that FOXC2, desmuslin, thrombomodulin and methylenetetrahydrofolate reductase have been found to be associated with varicose veins. Candidate gene approach requires a very detailed knowledge of the disease biology which unfortunately does not exist for varicose veins.

Synchronised use of technologies including genome‐wide association study (GWAS), metabonomics and micro‐RNA analysis have the potential to elucidate the molecular mechanism of the disease and identify the underlying genetic association.
Jakob von Uexküll (1864–1944)
Authors: Mildenberger Florian G
Published: September 2013

Uexküll, Jakob Johann Baron von (1864–1944), non‐Darwinian Baltic German biologist and philosopher, who introduced an environmental theory (‘Umweltlehre’) into biology. This theory differed from the contemporary concepts in many ways: it denied the existence of objectivity in life and research, referred to individuals instead of collectives, allowed analyses without commitment on either Darwinism or creationism, and permitted physiologists, biologists, behaviourists and psychologists work with it. Uexküll did not present his environmental theory at the beginning of his career around 1890, but only in the 1920s, after a long odyssey between Darwinism, anti‐Semitic elusions, prebehaviouristic approaches and semicreationistic theses. When most of his ‘German’ colleagues in biology were involved in national socialistic crimes, Uexküll and most of his junior scholars refused to support race biology. However, after 1945, when evolutionary synthesis was introduced into life sciences, his outdated non‐Darwinian biophilosophy was deployed from biological discussions.

Key Concepts:

Uexküll's environmental theory was based on the idea of a supernatural power in nature, which worked as a explanation for the existence of life at all.

Below supernatural power, biologists were able to analyse human and animal living worlds. Every life and his reflexes were explainable by Uexküll's functional cycle.

The environmental theory was usable for biologists, physiologists, behaviourists or psychologists, either Darwinistic or not. However, Uexküll hoped to use it as a proof for his anti‐Darwinian ideology.

Uexküll's environmental theory was later used for explaining the behaviour of patients in psychosomatic medicine or in semiotic disputes and discussions over philosophy of sciences. It is in use even today, though most of his contemporary colleagues have fallen apart.
Bassi, Agostino
Authors: Mazzarello Paolo , Garbarino Carla , Cani Valentina
Published: September 2013

Agostino Bassi was the first to translate aetiological ideas on the microbiological genesis of diseases into an actual research programme. Dedicated to his own, private naturalistic researches, Bassi demonstrated experimentally that a type of silkworm disease was due to a ‘parasitic fungus.’ He successfully isolated the parasite and used it to infect a healthy animal. He was also responsible for intuitions on the concepts of immunity, healthy carriers, predisposal to contracting infections and the dynamics of epidemics.

He understood that all infections are a product of parasitic beings that invade other living organic beings. This led to the microbiological theory of infectious diseases that would make enormous developments with the German, Robert Koch, and Frenchman, Louis Pasteur.
Anthropology
Authors: Black Sue , Randolph‐Quinney Patrick , Mallett Xanthé
Published: September 2013

Forensic anthropology can be described as the analysis of the human, or what remains of the human, for the medicolegal purpose of establishing identity. It is a multidisciplinary endeavor that applies the knowledge of biological anthropology and human osteology to cases where human remains are skeletonized, or where a detailed understanding of the growth and development, morphology, or norms of the human body can assist other disciplines in positive identification. This is achieved through the use of osteobiographical markers, which aid in the determination of four primary characteristics: skeletal age, sex, ancestry, and living stature. These are supplemented by markers of personal identity, which are likely to be specific to an individual, or that may be determined with varying degrees of statistical certainty. Such markers include both soft and hard tissue traits, some of which are biologically normal but specific to an individual, whereas others are pathological or abnormal, arising as the result of disease, trauma, surgical intervention, or cosmetic/aesthetic alteration.
Definition of stereotactic body radiotherapy
Authors: Guckenberger M. , Andratschke N. , Alheit H. , Holy R. , Moustakis C. , Nestle U. , Sauer O.
Published: September 2013

This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft für Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy.
Cloning, expression of a feruloyl esterase from Aspergillus usamii E001 and its applicability in generating ferulic acid from wheat bran
Authors: Gong Yan-Yan , Yin Xin , Zhang Hui-Min , Wu Min-Chen , Tang Cun-Duo , Wang Jun-Qing , Pang Qing-Feng
Published: September 2013

A cDNA gene (AufaeA), which encodes a mature polypeptide of the type-A feruloyl esterase from Aspergillus usamii E001 (abbreviated to AuFaeA), was cloned and heterologously expressed in Pichia pastoris GS115. One transformant, labeled as P. pastoris GSFaeA4-8, expressing the highest recombinant AuFaeA (reAuFaeA) activity of 10.76 U/ml was selected by the flask expression test. The expressed reAuFaeA was purified to homogeneity with an apparent molecular weight of 36.0 kDa by SDS-PAGE analysis, and characterized using the model substrate of methyl ferulate (MFA). The purified reAuFaeA was optimally active at pH 5.0 and 45 °C, and highly stable at pH 4.0–6.5 and 45 °C or below. Its activity was not significantly affected by metal ions tested and EDTA. The K  m and V  max of reAuFaeA towards MFA were 4.64 mM and 115.5 U/mg, respectively. High-performance liquid chromatography analysis showed that only 9.7 % of total alkali-extractable ferulic acid (FA) was released from destarched wheat bran by reAuFaeA alone. The released FA increased to 36.5 % when reAuFaeA was used together with a recombinant Aspergillus usamii GH family 11 xylanase A, indicating a synergistic interaction between them.
The importance of health co-benefits in macroeconomic assessments of UK Greenhouse Gas emission reduction strategies
Authors: Jensen Henning Tarp , Keogh-Brown Marcus R. , Smith Richard D. , Chalabi Zaid , Dangour Alan D. , Davies Mike , Edwards Phil , Garnett Tara , Givoni Moshe , Griffiths Ulla , Hamilton Ian , Jarrett James , Roberts Ian , Wilkinson Paul , Woodcock James , Haines Andy
Published: September 2013

We employ a single-country dynamically-recursive Computable General Equilibrium model to make health-focussed macroeconomic assessments of three contingent UK Greenhouse Gas (GHG) mitigation strategies, designed to achieve 2030 emission targets as suggested by the UK Committee on Climate Change. In contrast to previous assessment studies, our main focus is on health co-benefits additional to those from reduced local air pollution. We employ a conservative cost-effectiveness methodology with a zero net cost threshold. Our urban transport strategy (with cleaner vehicles and increased active travel) brings important health co-benefits and is likely to be strongly cost-effective; our food and agriculture strategy (based on abatement technologies and reduction in livestock production) brings worthwhile health co-benefits, but is unlikely to eliminate net costs unless new technological measures are included; our household energy efficiency strategy is likely to breakeven only over the long term after the investment programme has ceased (beyond our 20 year time horizon). We conclude that UK policy makers will, most likely, have to adopt elements which involve initial net societal costs in order to achieve future emission targets and longer-term benefits from GHG reduction. Cost-effectiveness of GHG strategies is likely to require technological mitigation interventions and/or demand-constraining interventions with important health co-benefits and other efficiency-enhancing policies that promote internalization of externalities. Health co-benefits can play a crucial role in bringing down net costs, but our results also suggest the need for adopting holistic assessment methodologies which give proper consideration to welfare-improving health co-benefits with potentially negative economic repercussions (such as increased longevity).
Opposition Growth in Dominant Party Systems: Coalitions in South Africa
Authors: Langfield Danielle
Published: September 2013

What is responsible for the decline of democratically dominant parties and the corresponding growth of competitive party systems? This article argues that, despite a ruling party's dominance, opposition forces can gain by winning important subnational offices and then creating a governance record that they can use to win new supporters. It focuses on South Africa as a paradigmatic dominant party system, tracing the increased competitiveness of elections in Cape Town and the surrounding Western Cape province between 1999 and 2010. These events show how party strategies may evolve, reflecting how party elites can learn from forming coalitions.
Steady water waves with vorticity: spatial Hamiltonian structure
Authors: Kozlov Vladimir , Kuznetsov Nikolay
Published: September 2013

Spatial dynamical systems are obtained for two-dimensional steady gravity waves with vorticity on water of finite depth. These systems have Hamiltonian structure and Hamiltonian is essentially the flow–force invariant.
Impact of geographical region on urinary metabolomic and plasma fatty acid profiles in subjects with the metabolic syndrome across Europe: the LIPGENE study
Authors: Walsh Marianne C. , McLoughlin Gerard A. , Roche Helen M. , Ferguson Jane F. , Drevon Christian A. , Saris Wim H. M. , Lovegrove Julie A. , Risérus Ulf , López-Miranda José , Defoort Catherine , Kieć-Wilk Beata , Brennan Lorraine , Gibney Michael J.
Published: September 2013

The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R2X: 0·33, Q2: 0·39) and plasma fatty acid (R2X: 0·32, Q2: 0·60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0·001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0·001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.
The Trickster in Egypt's January 25th Revolution
Authors: Armbrust Walter
Published: September 2013

The term “counter-revolution” evokes a straightforward contestation of political claims in a revolutionary situation. But contestation is not a zero-sum game: this side wins; the other side loses, and power remains the same. A revolutionary situation is unpredictable. New formulations of political claims may emerge in a protracted moment of “liminal crisis”—a kind of political ritual with no master of ceremonies capable of ending it. Indeed, the meaning of the political prize itself might be open to reinterpretation. My paper examines counter-revolution through the lens of Taufiq ‘Ukasha, an Egyptian talk show host and former member of the deposed National Democratic Party. Since the Revolution ‘Ukasha has become increasingly prominent as an unacknowledged spokesman for Egypt's Military Council, which assumed executive powers in the wake of the Mubarak regime's collapse. I argue that ‘Ukasha should not be understood simply as afilul—a remnant of the old regime. He is rather a “trickster,” a creature at home in the betwixt-and-between of open-ended liminality, and as such not an instrument of a socially grounded political power. In an environment in which the usual points of social and political orientation are called into question, the significance of a trickster is that he or she can become an object of emulation, an instrument of “schismogenesis”—the creation of a new social formation. A trickster, as a creature of pure liminality, is particularly prone to generating perverted forms of social knowledge. In ‘Ukasha's case, this new social formation is an unprecedented formulation of Egyptian militarism.
“Is this city yours or mine?” Political Sovereignty and Eurasian Urban Centers in the Ninth through Twelfth Centuries
Authors: Grinberg Lyuba
Published: September 2013

Numerous scholars have emphasized the “centrality” of Inner Asia to furthering our understanding of global, or cross-cultural phenomena, and the role of such phenomena in the preservation, modification, and transmission of historical experience. Yet the research has almost exclusively been carried out by specialists in Chinese civilization, and as one moves further away from the Chinese sphere of influence the notion of Eurasia as an integrated socio-political unit of historical analysis becomes more problematic. Here I attempt to bridge the western and eastern edges of the great steppe by focusing on a specific aspect of Inner Asian political culture—the phenomenon of shared sovereignty between military-based ruling dynasties and their urban constituencies—in the principalities of Rus' and the oases of Transoxiana, between the ninth and twelfth centuries. I propose that the dual administrative structure that developed in the two regions was an autochthonic, Eurasian state-formation, distinct from the city-state and imperial models, which emerged as a result of what Joseph Fletcher identified as “horizontal continuities.”
The Colonial Emergence of a Statistical Imaginary
Authors: Rowse Tim , Shellam Tiffany
Published: September 2013

Intellectual networks linking humanitarians in Britain, Western Australia, and New Zealand in the 1850s and 1860s operationalized the concept of native “protection” by arguing contra demographic pessimists that native peoples could survive if their adaptation was thoughtfully managed. While the population-measurement capacities of the colonial governments of Western Australia and New Zealand were still weak, missionaries pioneered the gathering of the data that enabled humanitarians to objectify natives as populations. This paper focuses on Francis Dart Fenton (in New Zealand), Florence Nightingale (in Britain), and Rosendo Salvado (in Western Australia) in the 1850s and 1860s. Their belief in the necessity of population statistics manifests the practical convergence of colonial humanitarianism with public health perspectives and with “the statistical movement” that had become influential in Britain in the 1830s. We draw attention to the materialism and environmentalism of these three quantifiers of natives, and to how native peoples were represented as governable through knowledge of their physical needs and vulnerabilities.
Geochronology, geochemistry and petrogenesis of the late Palaeoproterozoic A-type granites from the Dunhuang block, SE Tarim Craton, China: implications for the break-up of the Columbia supercontinent
Authors: YU SHENG-YAO , ZHANG JIAN-XIN , ZHAO XI-LIN , GONG JIANG-HUA , LI YUN-SHUAI
Published: September 2013

The discovery ofc. 1.77 Ga A-type granite in the Tarim Craton (TC) provides the first evidence that supports an extensional event related to fragmentation of the Columbia supercontinent in the late Palaeoproterozoic. We present laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) zircon U–Pb ages, Lu–Hf isotopic data and the whole-rock geochemical and Nd isotopic data of A-type granites in the Dunhuang area in the SE Tarim Craton. Zircon U–Pb dating for three granite samples indicate that they were emplaced atc. 1.77 Ga. Zircons from these granites have εHf(t) values ranging from –5.9 to 8.7, corresponding to two-stage model ages of 1.9–2.7 Ga. These granites exhibit the following petrological geochemical characteristics that are typical of A-type granite: (a) high content of SiO2and alkalis (i.e. high K2O + Na2O with K2O/Na2O > 1), enrichment of high-field-strength elements (HFSE) and rare Earth elements (REE) (except for Eu) and extreme depletion of Ba, Sr, P, Ti and Eu; (b) 10000×Ga/Al ratios in the Dunhuang granites of 3.5–4.4, with an average value of 3.79 which is similar to the global average of 3.75 for A-type granites; (c) the presence of characteristic minerals such as amphibole, sphene and perthite; and (d) zirconium saturation temperature results indicate that the Dunhuang granites have high initial magmatic temperatures in the range 887–950°C, similar to those of typical of A-type granites. Whole-rock εNd(t) values range from –2.5 to –6.2 andTDMmodel ages from 2.3 to 2.7 Ga. Nd–Hf isotopic and whole-rock geochemical data indicate that these granites were most likely derived from the late Archean crustal source in a post-collisional/post-orogenic extensional tectonic environment. The late Palaeoproterozoic A-type granites in the TC could be correlated with those of the North China Craton (NCC), India and the Canadian Shield, thus demonstrating extensional tectonics and break-up of the Columbia supercontinent.
Administration of dicyandiamide to dairy cows via drinking water reduces nitrogen losses from grazed pastures
Authors: WELTEN B. G. , LEDGARD S. F. , LUO J.
Published: September 2013

Oral administration of the nitrification inhibitor dicyandiamide (DCD) to ruminants for excretion in urine represents a targeted mitigation strategy to reduce nitrogen (N) losses from grazed pasture. A farmlet grazing study was undertaken to examine the environmental benefits of administering DCD in trough water to non-lactating Friesian dairy cows that consecutively grazed 12 replicated plots (each 627 m2with a grazing intensity of up to 319 cows/ha/day) during two grazing rotations in the winter of 2007 in the Waikato region, New Zealand. Nitrate-N (NO3−-N) leaching losses were measured using ceramic cup samplers (600 mm soil depth) and gaseous emissions of nitrous oxide (N2O) were quantified using a static chamber technique in the DCD and control treatments. Administration of DCD in trough water had no effect on daily water intake by dairy cows, which averaged 15 and 18 l/cow/day for the June and August grazing rotations, respectively. This resulted in a mean daily DCD intake of 46 and 110 g/cow/day, respectively. The DCD farmlet had significantly lower NO3−-N concentrations in leachate at the last three samplings, which reduced total NO3−-N leaching losses by 40% (from 32·0 to 19·2 kg N/ha). The DCD treatment reduced N2O emission rates compared to the control treatment following the August grazing, resulting in a 45% reduction in total N2O emissions relative to the control treatment (from 0·49 to 0·27 kg N2O-N/ha). This preliminary study highlights the potential for administering ruminants with DCD as an effective mitigation option for reducing N losses from agricultural systems.
Changes of rumen pH, fermentation and microbial population as influenced by different ratios of roughage (rice straw) to concentrate in dairy steers
Authors: WANAPAT M. , GUNUN P. , ANANTASOOK N. , KANG S.
Published: September 2013

The current study was designed to determine the effect of roughage to concentrate ratio (R : C) on rumen pH, fermentation and bacterial population in dairy steers. Four rumen fistulated dairy steers (170±20 kg) were randomly assigned according to a 4×4 Latin square design, in which the steers were fed with four dietary treatments with different R : C ratios of 0·8 : 0·2, 0·6 : 0·4, 0·4 : 0·6 and 0·2 : 0·8, respectively. All animals were kept in individual pens and received feed according to the respective R : C ratios at 0·025 body weight (BW)/d; urea-treated rice straw (prepared using 3·5 kg urea+100 kg water sprayed onto 100 kg of rice straw) was used as a roughage source. The experiment was conducted for four periods of 21 days each. During the first 14 days, feed intake was measured and the animals were then moved to metabolism crates for total urine and faecal collection for 7 days. Total dry matter intake (DMI) was similar among treatments. Energy intake increased as the proportion of concentrate in the diet increased. Apparent digestibilities of dry matter (DM), organic matter (OM) and crude protein (CP) were improved, while neutral detergent fibre (NDF) and acid detergent fibre (ADF) were reduced when the levels of concentrate increased. A decreasing ratio of R : C reduced rumen pH linearly, from 6·4 to 5·9 at 0·2 : 0·8. High levels of concentrate impacted on volatile fatty acids (VFA) molar proportions and decreased acetate (C2) linearly, while propionate (C3) was increased, leading to decreased C2 : C3 ratio. Numbers of protozoa, fungi and proteolytic bacteria were not affected by R : C ratio. Cellulolytic bacteria decreased linearly while amylolytic bacteria increased linearly with 0·60 and 0·80 concentrates. Quantitative polymerase chain reaction (qPCR) based on 16S RNA revealed thatFibrobacter succinogenesnumbers were increased when steers were fed with R : C ratio of 0·8 : 0·2. Conjugated linoleic acid (CLA)-producing bacteria, especially those ofButyrivibrio fibrisolvens, increased linearly with R : C ratios of 0·8 : 0·2 and 0·6 : 0·4, whileMegasphaera elsdenii, a lactate-utilizing bacterium and reported producer oftrans-10,cis-12 CLA increased linearly with R : C ratio of 0·8 : 0·2. In addition, microbial CP synthesis increased quadratically when steers were fed high levels of concentrate. However, the efficiency microbial N synthesis (EMNS) based on OM, truly digested in the rumen, was not affected by different R : C ratios. From the current study, it can be concluded that roughage to concentrate ratio of 0·4 : 0·6 had positive effects for the creation of healthy rumen (rumen pH and ecology), and improved energy intake and rumen fermentation, particularly propionic acid and microbial protein synthesis, in dairy steers fed urea-treated rice straw as a roughage source.