bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peroxisomes: Methods for Preparation
Authors: Islinger Markus , Fahimi H Dariush , Völkl Alfred 
Published: February 2014

Abstract

Peroxisomes are ubiquitous cell organelles particularly enriched in the mammalian liver and kidney. They contain oxidases producing hydrogen peroxide and catalase, which degrades it. The majority of 60 enzymes, so far, localised to mammalian peroxisomes is involved in lipid metabolism. However, they catalyse via β‐oxidation the degradation of saturated and unsaturated long and very long‐chain fatty acids and fatty acid derivatives including complex lipids, such as bile acids, leucotrienes and prostaglandins. On the other, they are engaged in the biosynthesis of lipids, such as polyunsaturated fatty acids, ether glycerolipids and polyisoprenoids. The essential metabolic role of peroxisomes in humans is shown quite plainly by inherited disorders, the so‐called peroxisomopathies, which are partly associated with severe peroxisomal dysfunctions. Commonly, peroxisomes are isolated by classical density gradient centrifugation. Meanwhile, however, advanced alternatives have been established, for example, immunochemical techniques as well as zonal free‐flow electrophoresis.

Key Concepts:

Peroxisomes are multipurpose organelles playing a pivotal metabolic role in humans as is revealed by a variety of inherited peroxisomal disorders.

They display a remarkable plasticity in both morphology and biochemistry not only between species and tissues but also regarding different regions of the same organ.

In mammalian and wild‐type yeast cells, peroxisomes are considered commonly to multiply by growth and division and usually do not form
de novo
. There is, however, growing evidence that peroxisomes can also arise
de novo
from the ER, and even new perspectives are provided on the potential contribution of the mitochondria to peroxisomal biogenesis.

The overall heterogeneity of peroxisomes and the consistency in the buoyant density of the subpopulations with other cell organelles hamper their purification by classic cell fractionation methods, inevitably calling for adequate techniques based upon alternative physicochemical traits.
Nicotinic Receptors
Authors: Marger Laurine , Itier Valérie , Bertrand Daniel 
Published: February 2014

Abstract

Fast neurotransmission in the central and peripheral nervous systems is mediated by the activity of ligand‐gated ion channels. Nicotinic acetylcholine receptors (nAChRs) belong to the family of cation‐permeable channels and result from the assembly of five subunits that form both the ligand‐binding site and the ionic pore. Sixteen genes encoding for these receptors have been identified in mammals and show differential expression throughout the body. Endogenously activated by ACh, nAChRs are the primary target of nicotine contained in tobacco leaves and mediate its addiction. The use of a partial agonist of nicotinic receptors significantly reduces craving and show good outcomes in smoking cessation. Spontaneous variations occurring in the genes encoding for nAChRs are associated with neurological diseases such as myasthenia gravis, to genetically transmissible epilepsies and to nicotine dependence. Dysfunction of the nAChR transmission is associated with diseases including schizophrenia, autism and neurodegenerative diseases such as Alzheimer's. Small molecules have recently shown beneficial outcomes in Alzheimer disease opening new avenues to treat neurological affections.

Key Concepts:

Neurotransmission is mediated by integral membrane proteins and can be subdivided into ligand‐gated ion channels and G‐coupled proteins.

Nicotinic acetylcholine receptors belong to the family of cationic ligand‐gated ion channels that comprises four transmembrane domains and result from the assembly of five subunit around an axis of pseudosymmetry.

Nicotinic acetylcholine receptors are key players in nicotine addiction and the primary target for this natural alkaloid that is contained in tobacco leaves.

Nicotinic acetylcholine receptors at the neuromuscular junction play a determinant role in mediating transmission from the motor nerve to the muscle cell. Impairment of these receptor function leads to myasthenia gravis, which can be decomposed in its most common form to an autoimmune disease and in rarer forms in mutations of one or more genes.

Dysfunction of the cholinergic system is associated with cognitive impairment and with neurological diseases such as schizophrenia, autism, genetically transmissible epilepsies and neurodegenerative diseases such as Alzheimer's.

The development of small chemical molecules such as the partial agonist varenicline is shown to help in smoking cessation programmes and, more recently, for α7 EVP‐6124 in the treatment of Alzheimer disease.
Evolution of Human Gene Expression Control
Authors: Boyd J Lomax , Wray Gregory A 
Published: February 2014

Abstract

The evolutionary history of our species is associated with the emergence of numerous phenotypic traits thought to be unique to humans. Comparative analysis of gene expression between human and nonhuman primates has revealed thousands of genes differentially expressed across multiple tissues. Comparative and functional genomic studies have implicated variation in
cis
‐regulatory regions, or enhancer elements, as a major component of species‐specific expression differences. Additionally, adaptive evolution between modern human populations has also been attributed to variation in
cis
‐regulatory regions of the genome. Despite these advances, the genetic basis of most derived human traits, population‐specific differences and heritable variation in gene expression remains unidentified. Gene regulation is known to proceed through the combinatorial interaction of multiple loci, acting cooperatively or redundantly, to regulate contextual gene expression in different tissues or at different times during development. The role of epistasis, the genetic interaction between loci, may, therefore, have a significant influence on the evolution of regulatory elements underlying trait difference between primate species and human populations.

Key Concepts:

Numerous highly conserved noncoding elements are rapidly evolving in humans and many function as tissue‐specific developmental enhancers.

Variation in phenotypic traits, including disease susceptibility, has been mapped to noncoding,
cis
‐regulatory loci.

Comparison of multiple primate genomes has enabled the identification of loci under both adaptive evolution (positive selection) and evolutionary constraint (negative selection).

Natural selection within protein‐coding and noncoding regions of genome is not uniform but more preferentially targets certain biological categories of genes.

The role of epistasis in the evolution of human gene expression control is unknown for most traits but may be significant.
Pseudogene Evolution in the Human Genome
Authors: Zhang Zhaolei , Zheng Deyou 
Published: February 2014

Abstract

Pseudogenes are those regions in a genome that have sequence similarity to functional genes but have decayed and have no obvious functions. It is estimated that the human genome contains more than 10 000 easily recognisable pseudogenes and many more fragmented sequences, that arose mainly through one of the following three mechanisms: duplication, retrotranposition and spontaneous loss of function. The majority of the human retrotransposed (i.e. processed) pseudogenes are primate specific, arising from a burst of retrotransposition activities approximately 45 Ma. Although most of the human pseudogenes are most likely too degenerated to perform a biological function, ∼20% of them exhibit evidence of transcriptional activity based on data from multiple genomic studies. Furthermore, a handful of pseudogene transcripts have been demonstrated experimentally to gain novel functions as noncoding
ribonucleic acids (RNAs)
, indicating that pseudogenes could be a reservoir for evolution innovation.

Key Concepts:

Pseudogenes are prevalent in the human genome and other mammalian genomes.

Most human pseudogenes are from past retrotranspositions occurring before the split of primate from other lineages.

Pseudogenes are a good source of DNA sequences for studying genome evolution.

Most human pseudogenes are most likely ‘dead’ but many of them can be transcribed.

Some human pseudogenes have adopted functions as noncoding RNAs.
Plant Pathogen Dispersal
Authors: West Jonathan S 
Published: February 2014

Abstract

Plant disease epidemics require plant pathogens to be dispersed to infect new hosts. Understanding dispersal is important for devising methods to improve detection and control of plant pathogens. This is not straightforward, as plant pathogens can be dispersed by air, rain, water or soil, and by vectors such as animals, pollen, various microbes, people and machinery and on infected plant material including seeds. Epidemics vary in time and space as a result of complex processes affecting inoculum availability and production, dispersal and survival processes, and also the coincidence of susceptible crop plants, which each interact with the weather. To reduce disease, exposure of crops to inoculum is often limited by separating crops in time and space, using crop rotation, including different varieties. A wide range of diagnostic methods are increasingly used to help with this by detecting plant pathogens before infection occurs to prevent introduction of exotic inoculum, or to improve applications of crop protection products.

Key Concepts:

Plant pathogens include fungi, protists (such as oomycetes and plasmodiophorids), bacteria, phytoplasmas, viruses and viroids. For plant disease epidemics to occur, these plant pathogens must be dispersed to infect new hosts.

Plant pathogens can be dispersed by air, rain, water, soil, by animals, people and machinery and through infected plant material including pollen and seeds.

A key method for crop protection is to limit dispersal by separating susceptible crops in time and space by crop rotation, use of different varieties, hygiene or management of inoculum and use of crop protection products (biologicals and pesticides) at key growth stages or when infection conditions are suitable.

Some pathogens that are dispersed by air are adapted to survive freezing temperatures, high UV light levels and desiccation, whereas others only remain viable for short periods or in certain less extreme conditions. Some may even induce ice nucleation to promote rainfall to return them to the ground.

Some plant pathogens are dispersed in rain‐splash, usually short distances but occasionally longer when combined with strong winds. Pathogens can be dispersed in water films and groundwater or rivers.

Insects and other invertebrates, pollen and protists may vector some pathogens, mainly viruses, viroids and phytoplasmas.

One of the main reasons for new introductions of plant pathogens to a territory is introduction by people, as infected plant material, infected seeds or as contamination on clothing, machinery, food or other imported materials. Various statutory quarantine regulations and inspections by plant health professionals aim to reduce introductions.

Climate change may help pathogens to establish in new territories where they were previously absent.
Gain‐of‐Function Mutants of p53 and Their Role in Tumourigenesis
Authors: Vaughan Catherine A , Deb Swati P , Deb Sumitra 
Published: February 2014

AbstractThe p53 gene is a tumour suppressor that is widely mutated in human cancers. Wild‐type p53 plays a pivotal role in preventingdeoxyribonucleic acid (DNA)damage and maintaining the integrity of the cell. Cells that contain mutant p53, however, are unable to prevent this damage and, in fact, become more oncogenic. Gain‐of‐function (GOF) mutant p53 has been shown to transactivate a number of genes that are part of cell growth and survival pathways and cause an increase in tumourigenicity. Knockin and transgenic mouse models have been utilised to explore the GOF phenotype of mutant p53. Currently, p53 cannot be targeted for cancer therapy, but recent studies have demonstrated the ability to reduce tumourigenicity in lung cancer cells addicted to their endogenous GOF mutant p53.Key Concepts:The p53 gene is the most frequently mutated tumour suppressor gene in cancer.WT p53 plays an active role in the cell cycle, DNA repair, apoptosis, and can function as a transcriptional activator.A wide array of functions of WT p53 are dependent on its transcriptional ability.Gain‐of‐function mutations are characterised by loss of the wild‐type tumour suppressor functions of p53 as well as gain of new oncogenic functions.Several groups have utilized mouse models to study mutant p53 gain of function in cancer.
B1‐ and CD5‐Positive B Cells
Authors: Renaudineau Yves , Bariller Edwige , Olivier Pers Jacques 
Published: February 2014

AbstractB1 (B1a/B1b) cells represent a population distinct from conventional B2 cells, which predominates the coelomic cavities. In contrast to B2 cells, B1 cells are selected by self‐antigens, and are chronically active in an autonomous B cell receptor pathway. B1 cells produce circulating IgM natural antibodies that provide ‘innate‐like’ protection against pathogens, contribute to the elimination of apoptotic cells and prevent B1 cell expansion. Furthermore, B1 cells are effective both in presenting autoantigens to T cells, and in inducing T cell activation and differentiation. The vast majority of B1 cells express CD5 and the new findings suggest that part of the B1 cell properties, as well as the capacity of B1 cells to contribute to the development of autoimmune diseases and chronic lymphocytic leukaemia, is related to the expression of the CD5 molecule.Key Concepts:B1 cells are a subclass of B cells.B1 cells are involved in the innate protection.B1 cells are first produced in the foetus.B1 cells predominate in the coelomic cavities in adults.B1 cells overlap incompletely with CD5+B cells in humans.
Incidental Findings in Genetic Research and Genetic Testing
Authors: Jackson Leigh 
Published: February 2014

Abstract

Incidental findings arise when clinically relevant genetic information about a research participant or patient is identified outside the scope of the original research objective or diagnostic test being performed. These findings can relate to carrier status for a heritable condition, misattributed paternity or increased susceptibility to a medical condition. The decision whether to disclose these findings to the research subject or patient is underpinned by many ethical, moral and potentially legal considerations. There is an urgent need for definitive guidelines for researchers and healthcare professionals. Major themes surrounding this issue include patient autonomy, patient welfare, harmful secrets and genetic literacy. The lack of relevant studies emphasises the urgent need for empirical investigations into the disclosure or nondisclosure of genetic incidental findings and the provision of guidelines to assist healthcare professionals and researchers.

Key Concepts:

Incidental findings are most likely to become more frequent due to advances in genome‐wide technology and decreases in the cost of testing.

Patient and participant autonomy must be considered in any strategy designed to manage incidental findings.

Patient and participant welfare should be a driving factor in decisions regarding disclosure of incidental findings.

Genetic secrets can be harmful to both the patient/participant and the healthcare professional.

The genetic literacy of healthcare professionals and public alike need to be considered when discussing genome‐wide testing technologies and attempts need to be made to increase knowledge across the board.

There is a lack of primary research data concerning patient and participant preferences regarding the management of incidental findings in research and the clinic.

Many clinician researchers have difficulty in separating their clinical and research obligations when genomic testing straddles the research–clinic interface.

There is an urgent need for coherent and ethical guidelines to address the management of incidental findings and assist researchers and clinicians in defining their legal, professional and ethical obligations.
Correlation analysis of genetic admixture and social identification with body mass index in a Native American Community
Authors: Norden‐Krichmar Trina M. , Gizer Ian R. , Libiger Ondrej , Wilhelmsen Kirk C. , Ehlers Cindy L. , Schork Nicholas J. 
Published: February 2014

ObjectivesBody mass index (BMI) is a well‐known measure of obesity with a multitude of genetic and non‐genetic determinants. Identifying the underlying factors associated with BMI is difficult because of its multifactorial etiology that varies as a function of geoethnic background and socioeconomic setting. Thus, we pursued a study exploring the influence of the degree of Native American admixture on BMI (as well as weight and height individually) in a community sample of Native Americans (n = 846) while accommodating a variety of socioeconomic and cultural factors.MethodsParticipants' degree of Native American (NA) ancestry was estimated using a genome‐wide panel of markers. The participants also completed an extensive survey of cultural and social identity measures: the Indian Culture Scale (ICS) and the Orthogonal Cultural Identification Scale (OCIS). Multiple linear regression was used to examine the relation between these measures and BMI.ResultsOur results suggest that BMI is correlated positively with the proportion of NA ancestry. Age was also significantly associated with BMI, while gender and socioeconomic measures (education and income) were not. For the two cultural identity measures, the ICS showed a positive correlation with BMI, while OCIS was not associated with BMI.ConclusionsTaken together, these results suggest that genetic and cultural environmental factors, rather than socioeconomic factors, account for a substantial proportion of variation in BMI in this population. Further, significant correlations between degree of NA ancestry and BMI suggest that admixture mapping may be appropriate to identify loci associated with BMI in this population. Am. J. Hum. Biol. 26:347–360, 2014. © 2014 Wiley Periodicals, Inc.
Engaging bodies in the public imagination: Bioarchaeology as social science, science, and humanities
Authors: Stojanowski Christopher M. , Duncan William N. 
Published: February 2014

ABSTRACTBioarchaeology is the contextual analysis of biological remains from past societies. It is a young and growing discipline born during the latter half of the twentieth century from its roots in physical anthropology and archaeology. Although often associated with the study of ancient diet and disease, bioarchaeology leverages variable temporal scales and its global scope to provide a uniquely comparative perspective on human life that transcends traditional boundaries of the natural sciences, social sciences, and humanities. Here, we explore the public face of bioarchaeology and consider the trends in publication practices that reflect diversifying research strategies.Bioarchaeology is a popular topic on web‐based science news aggregators. However, we identify a disconnect between bioarchaeology's traditional research emphases, emerging research foci, and findings that actually spark the public imagination. A majority of popular news articles emphasize basic discovery or “natural curiosities.” Publication data indicate the field also remains regionally focused with relatively little emphasis on nomothetic goals. Nevertheless, bioarchaeology can do more to leverage its historical perspective and corporeal emphasis to engage a number of topics with importance across traditional academic boundaries. Big data, comparative, multi‐investigator, interdisciplinary projects on violence, colonialism, and health offer the most obvious potential for driving research narratives in the biological and social sciences. Humanistic approaches that explore emotional connections to the past can also have merit. The diversity of research outlets and products indicates the field must embrace the importance of nontraditional activities in its value structure to maximize our potential in public arenas. Am. J. Hum. Biol. 27:51–60, 2015. © 2014 Wiley Periodicals, Inc.
Food and nutrition policy: A biological anthropologist's experiences from an academic platform
Authors: Pelletier David 
Published: February 2014

ObjectivesBiological anthropologists within academia and in other sectors are increasingly engaged in a variety of problem‐oriented research and in the design, implementation, or evaluation of policies and programs, domestically and abroad. Such work can have distinctive requirements in terms of disciplinary background, professional orientation, and professional development. This article explores these issues through the author's autobiographical account of a career in food and nutrition policy from within an academic nutrition department.MethodsThe article is guided by an analytical framework that compares eight projects in terms of their mode of knowledge production, academic impact, public impacts, and personal rewards. The projects range from village‐based surveys in Samoa and Malawi to food security planning in upstate New York communities, US policies on genetically engineered (GE) foods, and participant–observer research on nutrition policy development in low‐income countries.Results and ConclusionsThe cumulative experience reveals the importance of a commitment to problem‐solving, a transdisciplinary orientation, intellectual and methodological dexterity, ongoing engagement with policy actors and openness to emergent research questions, new research settings, and nontraditional funding sources. Am. J. Hum. Biol. 27:16–26, 2015. © 2014 Wiley Periodicals, Inc.
Overexpression of angiomotin in sinonasal inverted papilloma
Authors: Byun Jang Yul , Lee Sang Hag , Shin Jae Min , Baek Byoung Joon , Lee Jae Yong 
Published: February 2014

BackgroundAlthough inverted papilloma (IP) is one of the most common sinonasal tumors, its etiology and factors associated with tumor progression have not been fully determined. Generally, tumorigenesis or tumor growth requires angiogenesis to feed tumor cells. Angiomotin is a recently discovered protein that regulates migration and tubule formation in endothelial cells. It has been reported that angiomotin affects angiostatin (circulating inhibitor of angiogenesis), resulting in promotion of angiogenesis. Thus, we evaluated the expression and distribution of angiomotin in sinonasal IP, compared to normal control tissue.MethodsThe study included 10 subjects with sinonasal IP and 5 normal controls. Ethmoid sinus mucosa obtained during reduction of blowout fractures was used as a normal control. Reverse transcriptase–polymerase chain reaction (RT‐PCR), real‐time PCR, immunohistochemistry, and Western blot analysis were used to assess the expression, intensity, and distribution of angiomotin in tissues.ResultsPositive bands for angiomotin were seen in all specimens by RT‐PCR. The expression level of angiomotin was significantly upregulated in IP tissues versus normal sinus mucosa by real‐time PCR. Immunohistochemistry revealed positive reactions on endothelial cells of capillaries and small vessels within the tumor and normal tissues, but the positivity was significantly stronger in IP. Western blot analysis showed that expression levels of angiomotin were increased in IP compared to normal sinus mucosa.ConclusionAngiomotin, a novel protein in angiogenesis, was overexpressed in IP. Although it is not an etiological or initiating factor in tumor development, it seems to be associated with progression and growth of IP via promoting angiogenesis.