bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of Adaptation to High Altitude
Authors: Labie Dominique , Elion Jacques 
Published: April 2013

AbstractFrom the initial observation of Monge on the Andeans in the 1920s, polycythaemia and elevated haemoglobin (Hb) were considered the universal response to life at high altitude. However, this response is maladaptive, as excessive polycythaemia leads to the potentially lethal ‘chronic mountain sickness’. Highlanders in Tibet and Ethiopia revealed different phenotypes with Hb levels similar to those of sea‐level populations. Genome‐wide search for gene selection in these highlanders pointed on candidate genes encoding proteins belonging or closely related to the hypoxia‐inducible transcription factors (HIF) pathway. However, each population exhibits distinct sets of candidate genes suggesting convergent evolution on a candidate pathway rather than candidate genes. Complexity of the candidate genes in each population suggests that altering the HIF pathway globally needs to be balanced by other changes rescuing essential hypoxia‐regulated downstream processes. These observations open new avenues of investigations to uncover the molecular bases of adaptation to hypoxia that could also improve our understanding of common hypoxia‐induced maladies in lowlanders.Key Concepts:Moving out of Africa, man has colonised a very diverse array of environments including high altitude.The three most dramatic examples of long‐term high‐altitude residence are populations of the Andean Altiplano, the Tibetan plateau and the Ethiopian highlands.Highland populations have to cope with hypobaric hypoxia and cold and still maintain exercise, energetic metabolism and reproductive success.Based on the pioneer observation of Dr Carlos Monge on the Andean populations, polycythaemia and increased haemoglobin level have been considered the universal adaptive response to high‐altitude hypoxia for more than half a century.Tibetan and Ethiopian highlanders exhibit haemoglobin level comparable to sea‐level residents; thus elevated haemoglobin is not the universal response to hypoxia.Genome‐wide search for adaptive genes in the three paradigmal highland populations identified largely distinct patterns in each population, but converging towards the hypoxia‐inducible transcription factors (HIF) pathway.Analysis of genetic adaptation to high altitude in man expands the concept of converging evolution from candidate genes to candidate pathways.Complexity of the candidate genes in each highland population suggests that altering the central HIF‐mediated hypoxic signalling pathway globally may need to be balanced by other changes rescuing essential hypoxia‐regulated downstream processes.
Genetics of Alopecia
Authors: Inui Shigeki 
Published: April 2013

Abstract

A recent genome‐wide association study showed eight regions for alopecia areata (AA), including
CTLA4
,
IL‐2/IL‐22
,
HLA‐class II
,
UL16‐binding protein‐3
and
‐6
,
syntaxin 17
,
IL‐2RA
,
peroxiredoxin 5
and
Eos
. Candidate genes associated with androgenetic alopecia are divided into androgen‐related and ‐unrelated genes. The former includes
5
α‐
reductase isozymes
,
androgen receptor
and
ectodysplasin A2 receptor
, which is located close to androgen receptor (AR) gene, and possible AR coregulator such as
histone deacetylase 9
. The latter contains
PAX1
and
FOXA2
. Regarding congenital hypotrichosis, mutations in
EDA‐A1
,
EDAR
and
EDA‐RADD
,
p63
and
P‐cadherin
are pointed out for ectodermal dysplasia,
SPINK5
for Netherton syndrome, desmoglein 4,
lipase H (LIPH)
and
LPAR6 (P2RY5)
for localised autosomal recessive hypotrichosis,
lipase H (LIPH)
and
LPAR6 (P2RY5)
for autosomal recessive woolly hair,
keratin 74
for autosomal dominant woolly hair,
corneodesmosin
and
APCDD
for hypotrichosis simplex and
hairless
for Marie‐Unna hypotrichosis.

Key Concepts:

Recent studies using mainly genome‐wide association analysis revealed novel candidate genes associated with alopecia, providing informative explanation for the pathogenesis.

Genome‐wide association studies suggested the importance of innate and acquired immunity in alopecia areata pathogenesis and possibility of androgen‐independent pathogenic pathway in androgenetic alopecia.

Novel genes associated with congenital hypotrichosis have been found, providing new clues to search not only the pathogenesis but also molecular mechanism of normal hair growth.
Molecular Genetics of Rhabdomyosarcoma
Authors: Gallego Soledad , De Toledo Jose Sanchez , Roma Josep 
Published: April 2013

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. There are two main histologic subtypes, embryonal and alveolar, with different clinical behaviour and prognosis. Embryonal RMS is commonly localised with favourable prognosis, whereas alveolar RMS is more frequently metastatic and its prognosis is poor. These clinical differences reflect different molecular genetics. Alveolar RMS has recurrent reciprocal translocations that are absent in embryonal tumours. These translocations, t(2;13)(q35;q14) and t(1;13)(p36;q14), generate the fusion genes
PAX3–FOXO1
and
PAX7–FOXO1,
respectively. The resulting fusion proteins exert effects on differentiation, proliferation and apoptosis, thereby bestowing a survival advantage on RMS cells. Recent advances in the identification of the cell of origin of RMS and a deeper knowledge of deregulated signalling pathways offer an opportunity for novel therapeutic approaches for patients with this tumour.

Key Concepts:

Embryonal and alveolar RMS have different molecular and genetic features and different clinical behaviours.

Fusion‐negative alveolar RMS have expression profiles resembling those of embryonal RMS.

The chimeric proteins resulting from the characteristic translocations of alveolar rhabdomyosarcomas exert oncogenic effects.

Numerous signalling pathways are deregulated in rhabdomyosarcoma.

Rhabdomyosarcoma derives from myogenic progenitor cells that undergo malignant transformation under the effects of a regulator programme that involves
p53
and
Rb
pathways.
Somatic Genome Variations
Authors: Iourov Ivan Y , Vorsanova Svetlana G , Yurov Yuri B 
Published: April 2013

Abstract

The genome of somatic cells is susceptible to change through ontogeny. These variations can take a variety of forms and occur through different mechanisms. Stochastic intercellular variations of the genome are suggested to be involved in a number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging). However, somatic genome variations have been shown to be involved in pathogenesis of a broad spectrum of human diseases (from chromosomal and monogenic diseases to complex disorders). Nonetheless, the contribution of somatic genome variations to human biodiversity and disease is usually underappreciated. The latter is due to consistent questioning the possibility of techniques used for uncovering somatic genome variation. Therefore, technological aspects of studying intercellular variation of the human genome remain an additional important issue for understanding the role of somatic mosaicism in health and disease.

Key Concepts:

The cellular genome is highly variable both at molecular and at chromosomal level.

Somatic variation of the human genome is a likely mechanism for biodiversity either at intercellular or at interindividual level.

A number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging) seem to be mediated by somatic genome variations.

According to current concepts, the commonest type of intercellular genome variations are those manifested as changes of chromosome numbers (aneuploidy or polyploidy).

Somatic genome variations are known to contribute to pathogenesis of hereditary and chromosomal diseases.

Intercellular genome variation is a highly probable mechanism of complex disorders (i.e. diseases of the brain and immune system), pre‐natal mortality and cancer.

Understanding of the way to uncover somatic genome variations is an important issue for determining the contribution to intercellular/interindividual diversity in health and disease as well as their functional consequences.
Syphilis: Laboratory Aspects
Authors: Wright David J , Norris Steven J , Dhillon Rishi H‐P , Edmondson Diane G 
Published: April 2013

AbstractThe laboratory diagnosis of syphilis remains a challenge to physicians. The organism cannot be subcultured and dark‐field microscopy requires a skilled operator. Current routine assays rely on serological‐based techniques, which cannot distinguish syphilis from other treponemal infections such as yaws and pinta. False‐positive and false‐negative results can occur, as well as difficulties between differentiating between acute and chronic infection. Concomitant infection with human immunodeficiency virus (HIV) can also skew results. Molecular analysis with polymerase chain reaction (PCR) is promising but is still in its infancy and standardisation is required. Therefore in order to diagnose syphilis correlation with the history and clinical examination findings remain of paramount importance.Key Concepts:Models of the cyclical epidemics of syphilis, which have been proposed and the factors that influence their periodicity and size of recurrence.Comparison with the Treponema species that infect man with those from primates points to the origin of the disease, whereas study of their molecular structure throws light on treponemal biology.The role of serological tests in the diagnosis of syphilis is analysed. Rapid screening tests are contrasted with more sophisticated laboratory tests. An example of the latter is the place of confirmatory tests.The reasons for the gradual introduction of molecular tests like PCR into the diagnostic armoury and their current shortcomings are evaluated.The practical difficulties of manufacturing and introducing a syphilis ‘vaccine’ are addressed, despite the theoretical and experimental support for this approach.
Dayhoff, Margaret Oakley
Authors: Strasser Bruno J 
Published: April 2013

AbstractThe American physical chemist Margaret Oakley Dayhoff was one of the major figures in the early history of bioinformatics. In 1965, she published the initial edition of theAtlas of Protein Sequence and Structure, the first comprehensive, computerised and publicly available collection of protein sequences. It became a model for many subsequent sequence databases, including GenBank. Dayhoff developed several methods to analyse protein sequences and infer their evolutionary relationships, as well as computer models to simulate the composition of planetary atmospheres.Key Concepts:Margaret O. Dayhoff was one of the founders in the field of bioinformatics.Margaret O. Dayhoff created the first public comprehensive, computerised and publicly available database of protein sequences, TheAtlas of Protein Sequence and Structure(1965).TheAtlas of Protein Sequence and Structurewas the model for GenBank and many other molecular databases.TheAtlas of Protein Sequence and Structurewas a key tool for the development of molecular biology, molecular evolution and bioinformatics.TheAtlas of Protein Sequence and Structurewas tremendously successful among researchers, yet they were sometimes reluctant to contribute their data.
History of Research into Ageing/Senescence
Authors: Grignolio Andrea , Franceschi Claudio 
Published: April 2013

AbstractThe fact that people age and die has always stimulated extensive philosophical and medical investigations in all societies. The early theories of ageing that arose in ancient Greece and revived in the Middle Age saw old age as a consequence of the gradual consumption of the innate heat with the inevitable loss of body moisture, according to Hippocrates’ system of four‐humours (fifth century BC). The idea that senescence was itself an illness, the image of the aged body as a lamp in which life‐fuel has run out, the character alterations of elders, the attempt to prolong life through specific diet or by substituting damaged body parts were the main themes around which research into ageing and senescence revolved from the Renaissance to the eighteenth century. The fresh tools provided by evolutionary theory and molecular biology have opened new vistas, sometimes retrieving old conceptions, of the intimate mechanisms underlying the recent prolongation of life expectancy.Key Concepts:Early speculations on ageing were focussed on the bodily humoural imbalance and on the gradual loss of inner heat.Rejuvenating or stopping the ageing process was a major concerns of Medieval and Renaissance medicine.Prolonging human lifespan through specific dietetic regimens was a long running theme in the history of gerontology.Evolutionary approaches and molecular disciplines gave a new impetus to the researches into ageing.No more considered itself a disease, senescence is nowadays sees as a successful form of remodelling and adaptation to a lifelong series stressors.In the past decades, ageing researches have concentrated their efforts in four major directions: cellular theories, immune‐metabolic models, evolutionary explanations and molecular biology‐based approaches.
What is life? A Historical Survey
Authors: Pancaldi Giuliano 
Published: April 2013

AbstractNotions about life adopted within different cultural traditions reveal similarities. According to anthropologists, these similarities show that humans share a basic apprehension of the world, allowing them to tell the living from the nonliving. Some scholars consider this an outcome of evolutionary adaptation. The present article offers a survey of the views of life formulated over the past twenty‐four centuries that retain a bearing on the life sciences as they are practiced today. It will be argued that, at least since Charles Darwin and Louis Pasteur, notions about life and the uses of life in the social and economic sphere have been woven into a common fabric.Key Concepts:From Aristotle onward, answers to the question of what is life have displayed some recognisable, recurrent patterns.At least since Darwin and Pasteur, the notions about life and the uses of life in the social and economic sphere have been woven into a common fabric.During the twentieth century several circumstances favoured an intertwining between the research tools of the physicists and those of the biologists, often resulting in a gene‐centered view of life.Over the past few decades emerging specialties such as evo‐devo and systems biology have harboured growing dissatisfaction with the gene‐centered view.The achievements associated with the Human Genome Project at the turn of the century were technological as well as scientific.Answers to the question ‘what is life?’ are increasingly coming from technologically oriented approaches to the life sciences, sustained by the expanding bioeconomy.
Genome Evolution of
Trypanosoma cruzi
Authors: Souza Renata T , Marini Marjorie M , da Silveira José Franco 
Published: April 2013

Abstract

The protozoan parasite

Trypanosoma cruzi

is the etiologic agent of Chagas disease which is a major public health problem in Latin America.

T. cruzi

isolates have been classified into six main lineages (TcI–TcVI) based on genetics, phylogeographical and epidemiological studies. Its genome is complex, with a high variability among isolates, mainly as result of differences in the amount of repetitive sequences such as multigenic families encoding surface proteins and retrotransposons. Despite genome size variation and karyotype polymorphism,

T. cruzi

exhibits high conservation of chromosome structure with large syntenic groups conserved among all isolates. Comparison between

Trypanosoma brucei

and

T. cruzi

genomes suggests the occurrence of fusion and split events involving the chromosomes of these two species.

Key Concepts:

Trypanosoma cruzi
chromatin is poorly condensed during cell division, which precludes the use of conventional cytogenetic analysis.

Chromosomal bands can be separated by Pulsed‐Field Gel Electrophoresis (PFGE). A chromosomal band may contain co‐migrating chromosomes, which are not necessarily homologous.

The exact number of chromosomes remains unknown.

T. cruzi

is essentially diploid, although some larger aneuploid fragments have been described.

Six distinct

T. cruzi

lineages have been proposed on the basis of geographical, phylogenetic and epidemiological studies.

Large syntenic regions are conserved among

T. cruzi

isolates and also between trypanosomatids.

T. cruzi

lineages exhibit a striking conservation of chromosome structure.

The

T. cruzi

centromeric region consists of a GC‐rich strand‐switch domain composed mainly of degenerated retrotransposons.

T. cruzi

telomeres are composed of tandem repeats of the hexamer TTAGGG followed by a 189 bp species‐specific sequence.

The subtelomeric region is enriched with members of surface protein gene families and could be a site of generation of new variants of surface antigens.

The mapping of the syntenic regions on

T. cruzi

chromosomal bands provides evidence of the occurrence of fusion and split events involving

T. brucei

and

T. cruzi

chromosomes.
Genome Sequence of an Australian Kangaroo,Macropus eugenii
Authors: Deakin Janine E 
Published: April 2013

AbstractThe tammar wallaby (Macropus eugenii) is a model marsupial species that has been intensively used for research into various aspects of marsupial biology. Recently, it became one of only three marsupial species to have its genome sequenced. Comparisons of genome sequence from all three marsupials with those of other vertebrates have made it possible to begin identifying marsupial‐specific genome features. Our knowledge of the biology of the tammar wallaby has informed the interpretation of these unique features and provided insight into their evolution. Among these unique features are genes involved in the sophisticated marsupial lactation system and genes encoding for potent antimicrobial peptides. Comparisons of genome organisation have also provided insight into marsupial genome evolution.Key Concepts:Uncovering the genetic basis of unique marsupial features is now possible due to the availability of genome sequences for three marsupial species.The tammar wallaby is a model species used for studies into marsupial biology, making it possible to link genomic features with the biological characteristics.As the tammar wallaby genome was only lightly sequenced, other genomic resources such as transcriptome sequences and genome maps have enhanced the genome assembly.A number of novel genes are associated with the complex marsupial lactation system and immunity.Five novel genes have been identified on the marsupial Y chromosome.The organisation of the tammar wallaby major histocompatibility complex is vastly different to that of any other species studied to date.A decades old debate over chromosome number in the ancestral marsupial has been resolved by comparing genome organisation among the sequenced marsupials species and the outgroup species human and chicken.The wallaby genome assembly in combination with other genomic resources are proving valuable for the discovery of marsupial‐specific features.
Evolution of the Major Histocompatibility Complex: Insights from Characterisation of Marsupial Genes
Authors: Cheng Yuanyuan , Belov Katherine 
Published: April 2013

AbstractThe major histocompatibility complex (MHC) is a multigene family that plays an essential role in the innate and adaptive immune system. The MHC has been intensely studied in a variety of vertebrate species and comparative analyses of the MHC in distantly related species have revealed changes in gene complexity and organisation during the evolution of this gene cluster. Marsupials occupy a unique phylogenetic position that bridges the gap between eutherians and nonmammal species. Characterisation of MHC genes and genomic regions in marsupials has greatly improved our knowledge on MHC evolution, including our understanding of changes in genomic organisation, the effect of translocation or loss of genes on gene function and the influence of natural selection on genetic variations at MHC loci.Key Concepts:The genomic organisation of MHC class I genes differs between nonmammalian and eutherian species.The organisation of the marsupial MHC resembles that of nonmammals.Separation of class I genes from class II and antigen‐processing genes occurred after the divergence of marsupial and eutherian mammals.Classical class I genes are not linked to the MHC in the tammar wallaby.The nonclassical class I geneUKis conserved in marsupials and likely plays a significant functional role.Loss of a class II gene family in the Tasmanian devil may have an adverse impact on immunity in this species.Balancing selection acts to maintain high MHC diversity in the Kangaroo island tammar wallaby population.Selective sweeps may have contributed to the low MHC diversity in the Tasmanian devil.
Evolution of the Human Genome: Adaptive Changes
Authors: Crisci Jessica L , Jensen Jeffrey D 
Published: April 2013

Abstract

The study of human evolution is of interest to many both for the potential it has to improve our understanding of heritable disease, as well as for the possibility of illuminating evidence for adaptations that may help to tell the story of our origin. But uncovering evidence of positive selection at the genetic level has been a challenge. It remains unclear how much of the human genome has been affected by positive selection, what the main mechanism of selection is, and what types of patterns we should be looking for to identify adaptations. With whole‐genome sequencing and high performance computation, we are quickly shifting to a field in which data is no longer a limiting factor. Here we will discuss the progress that has been made towards these ends, explore the best examples of human‐specific adaptations to date, and discuss the implications of these findings within the context of classical population genetic theory.

Key Concepts:

An abundance of genomic data allows for a genotype‐first approach to discover selection in humans.

Ancient hominin genomic sequences provide a nearer outgroup to humans than chimpanzee, and therefore can help elucidate selective targets in humans.

Hard sweeps may have been rare in human evolution, whereas soft sweeps are a much more likely mechanism of selection.

The genomic signatures of sweeps, background selection, and demography all look similar and can be difficult to distinguish.

Genomic scans for selection make use of various signatures of selection and they rarely identify overlapping targets.

More accurate modelling of selection in humans is needed to find true signals of selection.
Impulsivity and Anxiety
Authors: Fernando Anushka 
Published: April 2013

Abstract

Impulsivity and anxiety are traits often found in many psychiatric disorders ranging from ADHD and bipolar disorder to post‐traumatic stress disorder (PTSD), social phobia and generalised anxiety disorder. Recent advances in both clinical and preclinical research propose further division of these two traits into distinct subconstructs. Specific cognitive tasks used across species suggest differing neurobiology underlying these processes, advocating their sub‐division. The further categorisation of these two traits is hoped to lead to specific treatments which can then be given in combination to the patient, rather than trying to treat a single disorder in its entirety. This is beginning to be explored with the use of complementary cognitive tasks in both animals and humans.

Key Concepts:

Psychiatry is advancing to treat defined symptoms rather than single disorders.

Impulsivity and anxiety are two traits thought to be distinct entities both in neural and psychological terms.

Division of these traits into subforms has been shown to correlate better with symptom diagnosis and therapeutic potential.

Establishment of these subforms is achieved with cross‐species tasks that model cognitive processes.

Future research using this approach aims to elucidate neurocognitive endophenotypes that may be symptomatic of more than one psychological disorder but readily treatable due to their defined characteristics.