bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocellular Carcinoma
Authors: Zhao Xuelian , Elmore Lynne W , Harris Curtis C , Wang Xin Wei 
Published: April 2013

Abstract

Primary liver cancer is the third leading cause of cancer‐related deaths and fifth most common cancer in the world. Globally, estimated 877 000 people develop liver cancer and an almost equal number die of it in 2007. The worldwide prevalence, unique geographic distribution and well‐established aetiologic factors of hepatocellular carcinoma (HCC) have provided a strong impetus for elucidating mechanisms underlying the development of this aggressive malignancy. A better understanding of the specific molecular features of hepatocarcinogenesis has revealed clues for novel preventative and therapeutic strategies. Of particular note, the recent extraordinary progress in the genetic and genomic understanding of this disease may shed light on the molecular mechanisms of HCC progression and this knowledge may offer great opportunities for improving the treatment and prevention of HCC.

Key Concepts:

HBV, HCV, alcohol, aflatoxin, diabetes and obesity constitute the main risk factors for HCC.

Prediction of prognosis and response to therapy, screening of high‐risk cases and science‐based therapy are the challenging tasks to improve clinical medicine.

HCC is a highly heterogeneous disease, which exists between primary tumours from different individuals as well as within a single carcinoma, where subpopulation can range from primitive, stem‐like cells to foci of well‐differentiated malignant epithelium.

Both genetic and epigenetic changes contribute to HCC, the understanding of mechanisms behind those changes may lead to personalised HCC medicine.
Genetic Counselling: Consanguinity and Cultural Expectations
Authors: Karbani Gulshan A 
Published: April 2013

AbstractIndividual and familial responses to diagnosis of serious genetic disorders are known to vary widely. But within some minority ethnic groups, expectations and norms may act as a further influence upon these responses and thus render genetic counselling more problematic than usual.This paper explores the implications of these cultural influences for ‘transcultural’ genetic counselling by focusing upon familial responses to diagnosis of a neuro‐degenerative disorder, Juvenile Sandhoff disease. Five out of seven cases in the UK health districts were linked to an extended family. These factors, along with ambivalent feelings around tests for ‘carrier’ status, can in part be explained by culturally mediated factors that included fears about the future marital and social prospects of children and the reactions from within the local communities. Genetic counselling in such cases thus not only needs to focus on the individual and family, but also reflect an awareness of these complex interactions between culture and attitudes. Recent development in the identification of gene, substrate deprivation and other potential treatments are beginning to be evaluated.Key Concepts:Genetic counselling: consanguinity and cultural expectations.Autosomal recessive mode of inheritance.Sandhoff disease is a life limiting neuro‐degenerative disorder characterised by an accumulation of GM2 gangliosidosises particularly in neurons. GM2‐Gangliosidosis, type 11 Hexosaminidases A and B deficiency. Children with Juvenile Sandhoff disease have ataxia, motor delay, walking deterioration, spasticity, and autism and learning difficulties.With random mating, it has been estimated that frequency of affected is 1 in 360000. However, literature (Drousiotouet al, Hum Genet. 2000 Jul; 107(1):12‐7) suggests potentially large variations in carrier frequency in different ethnic populations; prevalence of disease likely to be especially high in autozygous populations.Regional DNA laboratory has identified A missense mutation in ex11 (c.1376c>A (p.Asp459Ala) in the affected probands.Genetic testing could replace biochemical testing to ascertain the carrier status in families where Sandhoff disease has been diagnosed. This offers the opportunity for pre‐marital testing for carriers in addition to the service of pre‐natal diagnosis since this may be culturally acceptable and requested by these families.Despite some previous assumptions, contemporary UK minority families may be keen to take on screening and pre‐natal diagnosis.Many of these families are keen to take advantage of new treatments in future as they become available.These universal responses may be overlain by culturally mediated concern.Culturally skilled counsellors are needed to work successfully within our diverse population.
Protein Glycosylation, an Overview
Authors: Lisowska Elwira , Jaskiewicz Ewa 
Published: April 2013

Abstract

Glycosylation is the most common post‐translational modification of proteins. It is a complex process involving many functional proteins and resulting in a great diversity of carbohydrate–protein bonds and glycan structures. Biological role of glycosylation and molecular and genetic basis of glycosylation disorders have recently been extensively explored. Glycosylation of some proteins has a great impact on their structures and functions, and interactions of protein‐linked glycans with carbohydrate‐specific proteins (lectins) modulate many important biological processes. Alterations in glycosylation occur in many pathological states, and genetically determined defects in glycosylation are the reason of severe diseases. The goal of this short article is to signalise the variety of problems of this vast field of research.

Key Concepts:

Glycosylation is one of the most important posttranslational modification of proteins.

There are various types of carbohydrate–protein glycosidic linkage and a great variety of structures of protein‐linked oligosaccharides (glycans).

The glycosylation process involves multiple proteins which are direct products of genes.

Protein‐linked glycans, as indirect gene products, show microheterogeneity, in qualitative and quantitative sense.

Glycosylation of proteins has a great biological significance, carbohydrate–protein interactions are involved in many biological precesses.

Alterations of glycosylation in many diseases are used for diagnostic and prognostic purposes.

Genetically‐based defects in protein glycosylation are the reason of severe diseases that is a direct evidence for the importance of glycosylation.

Various glycosylation pathways are studied as potential targets for therapeutic purposes.
Pattern Searches in Protein Sequences
Authors: Koua Dominique , Lisacek Frédérique 
Published: April 2013

Abstract

Common amino acid patterns characterise protein families. The results of automated searches for such patterns are used to qualify protein structure and function and to explore evolutionary relationships. Considering the increasing number of
deoxyribonucleic acid (DNA)
and protein sequences generated by high‐throughput technologies, pattern search is commonly undertaken in the identification of new protein function or the elucidation of biological processes. A wide array of pattern matching methods has been implemented. They aim at identifying the constraints governing the occurrence of amino acids in protein regions. These constraints are expressed as probabilities or as templates or both to set the basis of automated search.

Key Concepts:

Protein families are structured on the basis of common sequence patterns.

Patterns constrain the nature and the position of amino acids.

Patterns are matched to templates called signatures or profiles.

Computing significant scores in addition to building realistic predictive models are the basic requirements for accurate identification by pattern matching.
Noonan Syndrome
Authors: Tartaglia Marco , Gelb Bruce D 
Published: April 2013

Abstract

Noonan syndrome is a genetic disorder inherited as an autosomal trait or occurring sporadically, characterised by short stature, dysmorphic facies, webbed neck, congenital heart disease or hypertrophic cardiomyopathy, skeletal anomalies, cryptorchidism and developmental delay. Missense mutations in the
PTPN11
gene, encoding the protein tyrosine phosphatase SHP2, cause approximately 50% of cases. SHP2 is a positive regulator of RAS/mitogen‐activated protein kinase (MAPK) signal transduction. Noonan syndrome‐associated
PTPN11
mutations typically have gain‐of‐function effects on SHP2 and RAS/MAPK signalling. Missense mutations in other genes encoding proteins in the RAS/MAPK pathway, including
SOS1
,
KRAS
,
NRAS
,
RAF1
,
BRAF
and possibly
MEK1
, also cause Noonan syndrome. In aggregate, mutations in these seven genes account for approximately 70–75% of Noonan syndrome. Genotype–phenotype associations have been established with respect to particular genes and even mutations underlying this disorder.

Key Concepts:

Noonan syndrome is an autosomal dominant, pleomorphic trait characterised by short stature, typical facial dysmorphia and cardiovascular defects.

Noonan syndrome is a genetically heterogeneous trait, caused by missense mutations in genes encoding proteins in the RAS/mitogen‐activated protein kinase pathway.

Most mutations causing Noonan syndrome have gain‐of‐function effects resulting in increased RAS signalling.

Strong genotype–phenotype associations exist for genes and even specific alleles for Noonan syndrome.

The seven Noonan syndrome genes identified to date account for approximately 70–75% of cases.
Taste: Central Processing
Authors: Scott Thomas R 
Published: April 2013

Abstract

The taste system monitors the chemical environment to detect carbohydrates, proteins, fats and salt to be consumed and toxins to be avoided. It activates reflexes for swallowing or rejection, and powerful hedonic mechanisms of pleasure or disgust. Electrophysiological and neural imaging studies are revealing taste's neural organisation. The weight of evidence implies that reflexive responses to tastants are orchestrated in the hindbrain, that a cognitive analysis of taste quality and intensity is completed in primary taste cortex, and that the reward value of a taste is added in secondary taste cortex and in ventral forebrain areas. Taste signals are also integrated with those from touch, smell, vision and the viscera to compose a sense of flavour.

Key Concepts:

The taste system protects us from ingesting toxins through rejection reflexes and a sense of disgust; it encourages us to consume nutrients through swallowing reflexes and a sense of pleasure.

A cognitive identification of taste is most likely made in primary taste cortex in the insula.

Taste information is integrated with that from other senses in cortical and ventral forebrain areas to create a sense of flavour.

Taste and flavour are imbued with hedonic tone – pleasure or disgust – in orbitofrontal cortex and ventral forebrain.
Anaerobes
Authors: Oren Aharon 
Published: April 2013

Abstract

A diverse world of microorganisms inhabits anaerobic environments on Earth, and these obtain their energy by fermentation or by anaerobic respiration, in which electron acceptors other than molecular oxygen drive the oxidation of organic compounds. We also know phototrophic and chemoautotrophic processes that function in the absence of oxygen. Collaboration of different groups of microorganisms can lead to degradation of complex organic matter also under anaerobic conditions, with carbon dioxide or a mixture of carbon dioxide and methane as the main products, depending on the availability of electron acceptors other than molecular oxygen, such as nitrate or sulfate. The different groups of anaerobes are essential for the functioning of the biogeochemical cycles of carbon, nitrogen, sulfur and other elements, and also play important roles in the production of fermented food products, treatment of organic wastes and other biotechnological processes.

Key Concepts:

Life developed on planet Earth in the absence of molecular oxygen (O
2
).

The anaerobic way of life is widespread in the prokaryotic world – in Bacteria as well as Archaea.

Permanently anaerobic environments include marine and freshwater lake bottom sediments, digestive systems, the deep subsurface and others.

Some protozoa can live anaerobically.

Recently a community of multicellular meiozoa that lives in permanently anoxic conditions was discovered in L'Atalante basin, 3.5 km below the surface of the Mediterranean Sea.

In the absence of molecular oxygen, many prokaryotes can use alternative electron acceptors, such as nitrate, sulfate, Fe(III) and others, for respiration (‘anaerobic respiration’).

When no suitable electron acceptor is available, energy can be gained by fermentation processes, in which ATP is gained by substrate‐level phosphorylation.

Complete anaerobic breakdown of organic matter is a cooperative process in which fermentative microorganisms, bacteria performing anaerobic respiration and methanogenic Archaea cooperate.

Hydrogen and acetate are key intermediates in many anaerobic degradation processes.
Biofuels: Microbially Generated Methane and Hydrogen
Authors: McAnulty Michael J , Vepachedu Venkata R , Wood Thomas K , Ferry James G 
Published: April 2013

Abstract

The production of methane (CH
4
) or hydrogen (H
2
) from renewable biomass by microorganisms growing anaerobically has the potential for contribution to independence from fossil fuels. Anaerobes function in Nature by converting biomass to CH
4
through food chains comprised of fermentative and acetogenic species, which decompose the complex biomass to H
2
, formate and acetate that are further metabolised to CH
4
by methanogens. Methanogens reduce the concentration of products to levels that permit the initial decomposition of biomass by fermentative and acetogenic species. Current H
2
production relies extensively on energy‐intensive fossil fuel sources. Photosynthetic and fermentative species offer more efficient routes for H
2
production. Although fermentatives have significantly higher production rates, they have lower yields of H
2
but may be a source of other valuable compounds that are synthesised along with H
2
. Further research must be conducted on obtaining H
2
from reductive pools of NAD(P)H to increase yields and increase economic competitiveness.

Key Concepts:

Methane production from biomass, an essential component of the global carbon cycle, requires a microbial food chain.

Methane‐producing species (methanogens) are terminal organisms of the food chain metabolising acetate, formate and H
2
that are metabolic products of species initiating decomposition of the biomass.

The methyl group of acetate is reduced to methane with electrons derived from oxidation of the carbonyl group.

Carbon dioxide is reduced to methane with electrons derived from oxidation of H
2
or formate.

Current hydrogen production relies on fossil fuel sources.

Photosynthetic hydrogen production yields are high, but rates are slow.

Dark hydrogen production rates are fast, but yields are low.

Higher yields through dark fermentation may be obtained using pathways that use NAD(P)H.

Additional products such as 1,3‐propanediol and ethanol may be obtained along with hydrogen in dark fermentations.
Water Transport Across Cell Membranes
Authors: Reuss Luis 
Published: April 2013

AbstractThis chapter is focused on the pathways and molecular mechanisms of water transport across the plasma membrane of animal cells. We discuss basic principles of water transport, including diffusion and osmosis and apply these concepts to the case of cell‐membrane water transport. The general conclusion is that diffusion and osmosis can explain water transport and that other mechanisms (e.g. cotransport) are less likely. Concerning the pathways for water movement across the plasma membrane, we consider the lipid bilayer, water‐selective pores (aquaporins – AQPs), nonselective larger pores, ion channels and membrane carriers. We conclude that the lipid bilayers and AQPs are the main pathways for transmembrane water fluxes, by solubility–diffusion and single‐file transport, respectively. Cell‐membrane water permeability varies considerably from cell to cell; high permeability denotes a fluid lipid bilayer and expression of AQPs. Low water permeability occurs when there is no aquaporin expression and membrane is rich in cholesterol.Key Concepts:Water transport across cell membranes occurs bydiffusionandosmosis.Theeffective osmolalityof a biological fluid is determined by the total solute concentrations and the solutes’ permeabilities, relative to water.The cell‐membrane osmotic water permeability varies from cell to cell, depending on the composition of the lipid bilayer and the presence or absence of water pores.The two main pathways for plasma‐membrane water transport are the lipid bilayer and water‐selective pores (aquaporins).Aquaporins are a large family of water pores; some isoforms are water‐selective whereas others are permeable to small solutes.Aquaporin 1 (AQP1), the best studied isoform, is present in the membrane as a tetramer; each monomer has a water pore.The pore of AQP1 is long and narrow (c. 2.8 Å diameter); water molecules lose their hydrogen bonds and permeate in single file.AQP‐mediated water permeability appears to be regulated mostly by controlling the number of molecules present in the membrane. Regulation of the ‘opening’ of the pores has also been proposed for some isoforms.AQP1 genetic deletion in mice causes profound alterations of renal function, consistent with a major physiological role of this protein.
Genetics and the History of the Basque People
Authors: López Saioa , Alonso Santos 
Published: April 2013

Abstract

The biological research on the origins of the Basque people was strongly motivated by the singularity of their language. Early investigations based on comparative craniometrics go back to the nineteenth century. These suggested the idea of a local evolution for the Basques. However, this approach soon proved to be unreliable. In the mid‐twentieth century, classical markers seemed to confirm that Basques were descendants of local Mesolithic Europeans who had avoided the impact of Near East Neolithic farmers better than other European populations.
Deoxyribonucleic acid
(DNA) typing and recent genome‐wide studies have allowed a more realistic reconstruction of the evolutionary history of populations. Further implications emerge from the genetic analysis of human remains from ancient archaeological sites. Several lines of evidence indicate that at least some Basque DNA lineages have evolved

in situ

, probably since pre‐Neolithic times. However, the place of the Basques in the European diversity landscape is still far from being completely elucidated.

Key Concepts:

Since mid‐twentieth century it has been speculated that Basques were descendants of local Mesolithic Europeans who had avoided the impact of Near East Neolithic farmers.

Traits under the influence of the environment are not reliable approaches to infer the evolutionary origins of populations. These include craniometrics and blood groups.

At least some Basque DNA lineages might have evolved
in situ
, probably since pre‐Neolithic times.

Evolutionary inferences made from modern DNA make substantial simplifications of human demographic history. Ancient DNA analysis can provide a clearer picture of our past and can enhance our chances to reconstruct our history.

The singularity of the Basques in the European diversity landscape is still controversial. Genetic heterogeneity within Basques is a possible confounder.
Genetics and the Origins of the Polynesians
Authors: Chambers Geoffrey K 
Published: April 2013

Abstract

Anatomically modern humans first arose in Africa. They rapidly spread out across the world with their earliest dispersers reaching as far as Australasia 40 000–60 000 years before present (ybp). Migration routes have been traced pretty thoroughly by molecular methods, but many controversies still remain. Recently debate has been focused on the relative importance of competing alternate pathways and the extent of interaction with other ancient peoples: Neanderthals and Denisovans. The origin of the Polynesian people who settled in Remote Oceania is a particularly long‐standing mystery. Surveys of genetic variation in these populations have helped to distinguish between competing theories arising from anthropology and linguistics. The genetic data show how maternal and paternal lineages combined approximately 3000 ybp giving rise to a new people who spoke Austronesian languages and developed a sophisticated technology for oceanic voyaging.

Key Concepts:

Anatomically modern humans came from Africa and dispersed widely in a relatively short time.

Dispersal patterns plus the timing and extent of gene flow from ancient people have all become controversial topics in recent years.

Pacific Island populations must be described in terms of culture and ancestry as well as their geographic location.

Genetic surveys are powerful tools for testing hypotheses about the migration histories of human populations.

Molecular markers can inform both pattern (origins and pathways) and process (hybridisation, gene flow, founder effects, etc.) in human evolution.

Maternal and paternal markers reveal different ancestors for Pacific people: Austronesian and Papuan, respectively.

Almost all preceding ‘Fast Train’ and ‘Slow Boat’ type models are captured as elements of an extended ‘Synthetic Total Evidence Model’.

Genetic studies of Pacific plants and animals support the emergent view from human genes, language and culture.

In any and all causal explanations of human history, known process elements must fully account for observed patterns.
Origins of the Australian and New Guinean Aborigines
Authors: van Holst Pellekaan Sheila M 
Published: April 2013

Abstract

Mitochondrial deoxyribonucleic acid
(mtDNA), Y chromosome and limited genomic studies indicate deep ancestry for both Australia and New Guinea peoples, with evidence for limited, shared genetic connection as well as ancient lineages specific to both places. Estimates of divergence from the Revised Sapiens Reference Sequence (Behar
et al.
, 2012) indicate that mtDNA haplogroups of living populations in Melanesia and Australia represent some of the oldest lineages outside Africa, founders having arrived there at least 50 000 years ago. Several entry points into Sahul during periods of glacial maxima might explain haplotype distribution. Distinctions between them and other near neighbours also indicate genetic isolation for long periods after sea levels rose. Phylogenies that explore genetic similarities/differences between peoples of Sahul and Asia suggest that migration routes through northern Asia as well as by a southern coastal route are likely scenarios, as no single regional source population is identifiable.

Key Concepts:

Australia and New Guinea were connected by a land bridge during periods of global glaciation forming a land mass known as Sahul, separated from Sunda.

Evidence indicates that people arrived in Sahul approximately 50–60 thousand years ago.

After the Last Glacial Maximum (LGM), Australia and New Guinea were gradually separated and the populations were relatively isolated from each other.

People dispersed throughout the Australian continent by 40 thousand years ago.

Participation in genetic research by descendants of the ‘First Sahulians’ is relatively rare and they are under‐represented in global studies.

There is resistance from some descendants of the First Australians for many reasons including distrust generated by poor research practices of the past.

Studies that include indigenous researchers as well as participants are likely to encourage, facilitate and improve representation.

Those Aboriginal Australians who have participated in genetic research have contributed valuable data that enrich the global story of human diasporation and their own communal and personal history.

Mitochondrial DNA (mtDNA) and Y‐chromosome analyses are particularly suitable for exploring recent human genetic history, whereas genome‐wide analyses are necessary for probing more deeply into population origins.

Complex population histories in Asia suggest different scenarios for likely routes and entry points for founding groups in Sahul.