bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase: Structure and Function
Authors: Shay Jerry W 
Published: October 2013

Abstract

In contrast to normal cells, tumour cells generally have short telomere lengths and show no continuing loss of telomere length with successive cell divisions, suggesting that telomere stability may be required for cells to escape from replicative senescence and proliferate indefinitely. Most, but not necessarily all, malignant tumours are immortal to sustain their growth, thus, the cellular ribonucleoprotein (reverse transcriptase) enzyme complex termed telomerase may be a rate‐limiting step required for the continuing proliferation of advanced cancers. Telomerase, the enzyme that completes
deoxyribonucleic acid (DNA)
replication at the termini of eukaryotic chromosomes, is an important factor in DNA replication, chromosomal stability and tumorigenesis.

In human tumours, telomere length is maintained by a balance between processes that lengthen telomeres (telomerase) and processes that shorten telomeres (lack of complete lagging DNA strand synthesis ‘end replication problem’ and other end processing events). Telomerase stabilises telomere length by adding TTAGGG repeats onto the telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres that occurs in its absence. As telomerase is expressed in almost all human cancers, approaches for inhibiting telomerase as a target for cancer therapeutics are currently progressing through clinical trials.

Key Concepts:

Telomeres, the ends of human chromosomes progressively shorten throughout life in all dividing human cells and when critically shortened become ‘uncapped’ leading to a DNA damage signal and then undergo growth arrest termed replicative senescence (cell ageing).

A hallmark of cancer cells is unlimited cell growth.

Advanced cancer cells accomplish immortality almost universally by activating or upregulating the ribonucleoprotein complex termed telomerase.

Telomerase is composed of two essential components, TERT (reverse transcriptase component) and TERC (functional or template RNA that recognises the ends of chromosomes).

Telomerase is expressed during early human development and remains silent in almost all human tissues except transiently amplified stem cells throughout life.

Approximately 90% of all human cancers express telomerase activity.

A small fraction of human tumours do not express telomerase and some of these may engage a DNA recombination mechanism to maintain telomeres termed ALT, alternative lengthening of telomeres.

Introduction of hTERT into normal telomerase silent cells is sufficient to immortalise cells in appropriate culture conditions without the cells becoming cancerous.

As telomerase is almost a universal oncology target, inhibiting telomerase should be a potent anticancer therapeutic target.
Comparing the Human and Sea Urchin Genomes
Authors: Cameron R Andrew 
Published: October 2013

Abstract

To compare the genomes of humans and sea urchins seems, at first glance, awkward. The human body is bilaterally symmetrical with a complex head containing many sensory structures, whereas the sea urchin has radial symmetry and a globose form with no suggestion of a head. However, sea urchins belong to a group of animals (the echinoderms) that lies on the same major branch of the tree of life (the deuterostomes) to which humans belong. As echinoderms diverged very early from the major lineage of the deuterostomes, their genomes reflect the basic qualities of this lineage and inform to a deep reach of time the evolutionary changes leading to the human genome. Even though the sea urchin form differs radically from that of vertebrates, they share many of the same gene families. Indeed, the invention of new genes in this evolutionary path is subordinate to the diverse changes in the abundance of genes in existing families.

Key Concepts:

The relative proximity of sea urchins to humans on the deuterostome branch of the evolutionary tree renders them a good comparison to humans for gene and genome evolution.

The sea urchin genome is one‐quarter the size of the human but has about the same number of genes.

Gene comparisons between these distantly related species show that differences in body plans result from spatial and temporal differences in gene activity rather than the possession of different genes.

The sea urchin HOX gene cluster is modified from the linear arrangement found in humans.

Without an adaptive immune system, the sea urchin appears to use a huge expansion in innate immune genes.
Speciation Genes
Authors: Mensch Julián , Frankel Nicolás , Hasson Esteban 
Published: October 2013

Abstract

Even though there is no universal criterion for species definition, the key event in speciation research is the advent of reproductive isolation or barriers that prevent gene flow between populations. The search for genetic factors underlying isolating barriers is the field of speciation genetics. The development of sophisticated methods of genetic analysis coupled with statistical advances allowed a finer dissection of the genetic factors underlying the origins of species down to the level of the individual loci and even at the
deoxyribonucleic acid (DNA)
‐sequence level. Traditionally, speciation geneticists concentrated, almost exclusively, on genes causing hybrid incompatibilities (especially intrinsic postzygotic barriers). However, barriers to gene flow caused by speciation genes can arise at multiple prezygotic and postzygotic life‐history stages. Thus, a general definition of speciation genes should refer to those genes that contributed to the splitting of two lineages by reducing the amount of gene flow between them.

Key Concepts:

The evolution of barriers to genetic exchange between groups is the crucial event for the origin of new sexually reproducing species.

Barriers to gene flow can be divided in two main categories: (i) prezygotic that preclude the formation of hybrid offspring and (ii) postzygotic that later prevent the success and propagation of hybrid offspring.

The identification and characterisation of genes that contribute to the interruption of gene flow between populations is currently one of the main focuses in the field of speciation.

Speciation genes are the genes that contributed to the splitting of two lineages by reducing the amount of gene flow between them.

The most solid evidence that a gene causes reproductive isolation combines fine mapping studies with genetic manipulation experiments (such as positional cloning, gene replacement or knockout, gene expression assays and transgenic manipulations).

Alleles underlying hybrid incompatibilities between species may arise by neutral or nearly neutral processes or may be a direct consequence of positive selection or a byproduct of adaptive evolution.
Ras Mutations in Cancer
Authors: Barault Ludovic , Lamba Simona , Di Nicolantonio Federica 
Published: October 2013

Abstract

Mutations affecting the three isoforms of the RAS gene – KRAS, HRAS and NRAS – represent the most common oncogenic event in several cancer types. RAS mutations lead to constitutive activation of the corresponding protein and contribute to different hallmarks of cancers, including increased proliferation and resistance to apoptosis. Activating mutations in
KRAS
are currently used in the clinic to exclude colorectal cancer patients from treatment with ineffective epidermal growth factor receptor targeted‐based therapies. Future studies are needed to fully elucidate the role of all
RAS
oncogenic variants in cancer biology, as well as to assess the potential prognostic and predictive value of individual
RAS
genetic alterations in clinical settings other than colorectal cancer.

Key Concepts:

RAS in human consists in 4 isoforms (KRAS4A, KRAS4B, NRAS, and HRAS) encoded by 3 genes (
KRAS
,
NRAS
, and
HRAS
).

Isoforms of the
RAS
gene (
KRAS
,
NRAS
,
HRAS
) are the major oncogenes mutated in several cancer types.

Mutations in
RAS
family genes lead to constitutive protein activation by inhibition of the catalytic reaction which converts active RAS–GTP to inactive RAS–GDP.

Different types of mutations occur in different cancers.

Mutations in
RAS
family genes may differ in terms of biochemical effectors, biological activities and prognostic or predictive value.
Signalling via Single‐Pass Transmembrane Proteins
Authors: Pahl Matthew C , Askinazi Olga L , Hamilton Catherine , Cheng Irene , Cichewicz Karol , Kuhn Jason , Manohar Sumanth , Deppmann Christopher D 
Published: October 2013

Abstract

Single‐pass transmembrane proteins (TM1) are a diverse group of proteins characterised by a single transmembrane domain. In total, the authors found approximately 1300 TM1 proteins in the human genome, most of which have characterised functions. The extracellular domains of these proteins range up to 22 000 amino acids with an average size being six times larger than intracellular domains. This suggests that these proteins have evolved the capacity to bind a wide array of ligands and substrates. Consequently, these proteins are involved in many processes, such as adhesion, migration, growth and cell death, among others. Although many act as receptors for first messengers (extracellular signalling molecules), they can also serve as ligands, adaptors, proteases and coreceptors. Herein, the authors provide a broad overview of these different roles along with examples of their involvement in pathological and physiological situations.

Key Concepts:

Single‐pass transmembrane proteins participate in signalling in a variety of ways, either as ligands, receptors, enzymes coreceptors and/or adaptors.

TM1 proteins appear to have undergone evolutionary expansion as a function of body plan complexity.

The extracellular domains of TM1 proteins cluster well based on family, whereas the intracellular domains do not.

TM1 proteins are adapted to bind very large substrates/ligands compared with other receptor families (ion channels and GPCRs).

TM1 have roles in every organ system and are particularly important in the immune and nervous systems.
Molecular Genetic Analysis of Ménière's Disease
Authors: Hietikko Elina , Kotimäki Jouko , Männikkö Minna 
Published: October 2013

AbstractMénière's disease (MD) is an inner ear disease characterised by tinnitus, vertigo and sensorineural hearing loss. The exact aetiology of MD is unknown but it is generally considered as a multifactorial disease. The role of genetic factors in the development of MD has been well documented. Familial clustering of MD has been observed in several studies and the proportion of familial cases is estimated to be 5–23.5%. Single locus on chromosome 12p12.3 has been reported in Swedish MD families. In addition, several inconclusive candidate‐gene analyses have been performed. At the moment, knowledge of genetic factors associated with MD is modest. Molecular genetic study of MD is complicated by genetic and clinical heterogeneity and diagnostic challenges. However, modern genetics may be useful in discovering new pathways associated with the pathophysiology of MD in the future.Key Concepts:The knowledge of genetic factors associated with MD is currently modest.Genetic and clinical heterogeneity, diagnostic challenges, multifactorial origin and late onset of MD create challenges to the molecular genetic analysis of the disease.Family‐based studies may assist to reduce genetic and phenotypic heterogeneity to identify molecular mechanisms or pathways involved in the pathogenesis of MD.Candidate‐gene analysis is an ineffective way to study the genetics of MD and future genetic studies should emphasise the usage of linkage analyses and next‐generation sequencing as well as studying epigenetic pathways.A strong interdisciplinary research environment is needed to successfully study molecular genetics of MD. Combined efforts of highly skilled otologists, geneticists and statisticians are needed to overcome the difficulties in the molecular genetic analyses of MD. To achieve power for genetic studies, a greater number of subjects are needed. This shortcoming may be corrected by an international cooperation between study groups.
Studying Wound Repair in the Mouse
Authors: Tan Nguan S. , Wahli Walter 
Published: October 2013

AbstractAnimal models of wound healing provide vital insights into the mechanisms and pathophysiology of cutaneous wound repair and are a crucial part of clinical research into the development of new strategies and approaches to rational wound therapy. Although considerable biological variation in the wound healing response exists even among inbred animal strains, consistent surgical procedure and wound analysis can yield significant conclusions. Many different aspects of the healing process can be characterized and quantified in a reproducible, controlled environment. Here, we detail methods for full‐thickness excisional and incisional wounding and for analysis of wound biopsies. Curr. Protoc. Mouse Biol. 3:171‐185 © 2013 by John Wiley & Sons, Inc.
Critical Literacy and Critical Discourse Analysis
Authors: Valdez Paolo Nino 
Published: October 2013

Abstract

Critical discourse analysis is an area of scholarly inquiry that attempts to unravel manifestations of power, ideology, and control embedded within texts. Its socially oriented focus in the analysis of language has established the importance of reflexivity in accounting for the non‐neutrality of language in real‐life contexts. Typical investigations of
CDA
fall under the rubric of political discourses concerning government on issues of difference (race, sex, and age), media discourse's influence in representing individuals and different sectors of society, and influence of other domains in colonizing institutional discourses.

On the other hand, critical literacy (
CL
) is an approach to life and learning. Specifically,
CL
's actualization is the empowerment of the learners as active agents of change through meaningful inquiry and dialogue to achieve true progress. Scholars who espouse
CL
firmly believe that practitioners need to engage in a politics in their work in order to achieve authentic change—one that benefits all members of the community.
The Dictionary as a Tool in Language Learning
Authors: East Martin 
Published: October 2013

Abstract

The dictionary, according to Kirkness, is

an essential source, if not indeed the principal source, of information on language for all members of literate societies who might have questions on any aspect of the form, meaning, and/or use of a word or words in their own or in another language. (p. 54)

Seen from this perspective, dictionaries are vital tools invoked by language users in a range of situations when they are seeking clear and definitive answers on problems they encounter with language in use.
Portfolio Assessment
Authors: Hung Shao‐Ting Alan , Huang Heng‐Tsung Danny 
Published: October 2013

Abstract
Portfolio assessment represents a form of alternative assessment and, as its name reveals, assesses learning performance via evaluating portfolios. As defined by Genesee and Upshur, a portfolio refers to “a purposeful collection of students' work that demonstrates . . . their efforts, progress and achievement in given areas”(p. 99) and might include such artifacts as writing samples, reading logs, drawings, journals, personal reflections, and teacher and student comments on students' progress, among others.

Portfolio assessment came into prominence largely as a response to the need to transcend standardized testing and, more importantly, the need to integrate instruction and assessment. As Hamp‐Lyons and Condon asserted, a portfolio

provides an instrument that incorporates the products of instruction and that can, if the assessment is designed carefully, provide an evaluation that feeds back into the process of instruction . . . Perhaps the greatest theoretical and practical strength of a portfolio, used as an assessment instrument, is the way it reveals and informs teaching and learning (pp. 3–4).
Vocabulary and Listening
Authors: van Zeeland Hilde 
Published: October 2013

Abstract

Second language (
L2
) listening has received relatively little research attention, and this is also the case in the field of vocabulary. Considerably fewer vocabulary studies have been conducted in the context of listening than reading. However, the existing research has emphasized the reciprocal importance of listening and vocabulary: vocabulary knowledge is a prerequisite for listening comprehension, and listening can serve as a useful source for vocabulary acquisition. This entry provides an overview of the existing research by considering both points in turn: (a) the role of vocabulary knowledge in listening (their relationship, the vocabulary requirements for listening, and vocabulary recognition in listening); and (b) the acquisition of vocabulary from listening.
Independent associations between cardiorespiratory fitness, waist circumference, BMI, and clustered cardiometabolic risk in adolescents
Authors: Buchan Duncan S. , Young John D. , Boddy Lynne M. , Baker Julien S. 
Published: October 2013

ABSTRACTObjectivesThe purpose of this study was to examine the independent associations between measures of adiposity and cardiorespiratory fitness (CRF) with clustered cardiometabolic risk in adolescents.Methods209 adolescents (139 boys), aged 15–17.5 years participated. Participants completed anthropometric measurements [height, weight, waist circumference (WC)] whilst the 20 m fitness test was used to assess CRF. Additional measures included systolic blood pressure, triglycerides, ratio total cholesterol/high‐density lipoprotein cholesterol, insulin resistance (HOMA), interleukin‐6, C‐reactive protein (CRP), and adiponectin.ResultsPartial correlations revealed weak to moderate negative associations for body mass index (BMI) and WC with CRF (r = −0.295 and –0.292, P < 0.001) and adiponectin (r = −0.227 and −0.262, P < 0.05). Weak to moderate positive associations were evident for BMI with CRP, and cardiometabolic risk (r = 0.274, and 0.283, P < 0.05, respectively). Weak to moderate positive associations were apparent for WC with CRP and triglycerides (r = 0.240 and 0.254, P < 0.05), whilst moderate to large associations were evident for WC with clustered cardiometabolic risk (r = 0.317, P < 0.05). Regression analyses revealed that BMI was positively associated with cardiometabolic risk (β = 0.243, P < 0.001). Further analysis whilst additionally controlling for WC and CRF strengthened this association (β = 0.352, P < 0.001). Finally, participants in the least‐fit quartile for CRF had significantly poorer cardiometabolic risk scores than those in the other quartiles.ConclusionBMI and not CRF was independently associated with cardiometabolic risk. Reducing BMI appears essential to minimize cardiometabolic risk during adolescence. Am. J. Hum. Biol. 26:29–35, 2014. © 2013 Wiley Periodicals, Inc.
Associations between insulin and heart rate variability in police officers
Authors: Charles Luenda E. , Andrew Michael E. , Sarkisian Khachatur , Shengqiao Li , Mnatsakanova Anna , Violanti John M. , Wilson Mark , Gu Ja K. , Miller Diane B. , Burchfiel Cecil M. 
Published: October 2013

ABSTRACTObjectiveLow heart rate variability (HRV) has been linked to cardiovascular disease. Our objective was to examine the cross‐sectional association between insulin and HRV.MethodsInsulin levels were measured in 355 nondiabetic officers from the BCOPS study, following a 12 h fast. HRV was performed according to methods published by the task force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology for measurement and analysis of HRV. Mean values of high (HF) and low frequency (LF) HRV were compared across tertiles of insulin using ANOVA and ANCOVA; p‐values were obtained from linear regression models.ResultsHigher mean levels of insulin were significantly associated with lower (i.e., worse) mean levels of HRV before and after risk‐factor adjustment. The results for HF HRV (ms2) were as follows: 1st insulin (µU/ml) tertile (156.3; 95% confidence interval (CI) = 128.6–189.9); 2nd tertile (154.3; 95% CI = 124.3–191.5); 3rd tertile (127.9; 95% CI = 105.0–155.8), p for trend = 0.017. Results with LF HRV were similar to HF HRV. Insulin was also inversely and significantly associated with HRV among officers with BMI ≥25 kg/m2, with ≥25.5% body fat, and among those who reported low (<median) physical activity scores.ConclusionsIn this cohort, insulin levels were inversely and significantly associated with both HF and LF HRV, especially among those with higher levels of obesity and lower levels of physical activity, suggesting associations with autonomic nervous system function. Prospective studies of this association in other populations are warranted. Am. J. Hum. Biol. 26:56–63, 2014. © 2013 Wiley Periodicals, Inc.
Technical note: False catastrophic age‐at‐death profiles in commingled bone deposits
Authors: Sołtysiak Arkadiusz 
Published: October 2013

ABSTRACTAge‐at‐death profiles obtained using the minimum number of individuals (MNI) for mass deposits of commingled human remains may be biased by over‐representation of subadult individuals. A computer simulation designed in the R environment has shown that this effect may lead to misinterpretation of such samples even in cases where the completeness rate is relatively high. The simulation demonstrates that the use of the Most Likely Number of Individuals (MLNI) substantially reduces this bias. Am J Phys Anthropol 152:554–557, 2013. © 2013 Wiley Periodicals, Inc.
Body size and premolar evolution in the early‐middle eocene euprimates of Wyoming
Authors: Jones Katrina E. , Rose Kenneth D. , Perry Jonathan M.G. 
Published: October 2013

ABSTRACTThe earliest euprimates to arrive in North America were larger‐bodied notharctids and smaller‐bodied omomyids. Through the Eocene, notharctids generally continued to increase in body size, whereas omomyids generally radiated within small‐ and increasingly mid‐sized niches in the middle Eocene. This study examines the influence of changing body size and diet on the evolution of the lower fourth premolar in Eocene euprimates. The P4 displays considerable morphological variability in these taxa. Despite the fact that most studies of primate dental morphology have focused on the molars, P4 can also provide important paleoecological insights. We analyzed the P4 from 177 euprimate specimens, representing 35 species (11 notharctids and 24 omomyids), in three time bins of approximately equal duration: early Wasatchian, late Wasatchian, and Bridgerian. Two‐dimensional surface landmarks were collected from lingual photographs, capturing important variation in cusp position and tooth shape. Disparity metrics were calculated and compared for the three time bins. In the early Eocene, notharctids have a more molarized P4 than omomyids. During the Bridgerian, expanding body size range of omomyids was accompanied by a significant increase in P4 disparity and convergent evolution of the semimolariform condition in the largest omomyines. P4 morphology relates to diet in early euprimates, although patterns vary between families. Am J Phys Anthropol 153:15–28, 2014. © 2013 Wiley Periodicals, Inc.