bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Hominin Social Systems
Authors: Grove Matt 
Published: September 2013

AbstractThis 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

Abstract

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

Abstract

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

Abstract

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

AbstractGenetic 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

AbstractInflammatory 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

AbstractThe 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

Abstract

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

Abstract

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

AbstractUexküll, 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

Abstract
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

AbstractForensic 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.