bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomes during Cell Division
Authors: Liu Song‐Tao , Allison David C , Nestor‐Kalinoski Andrea L 
Published: November 2010

Abstract

In mitosis, duplicated
deoxyribonucleic acid
(DNA) goes through a condensation/decondensation cycle. This is followed by nuclear envelope dissolution, mitotic spindle assembly, migration of the sister chromatid pairs to the metaphase plate, division and segregation of identical sets of chromosomes into daughter nuclei and nuclear envelope reformation. This process results in the formation of two genetically identical daughter cells. Dynamic structural changes and the mitotic spindle‐mediated movement are two major features that occur to chromosomes during cell division. Both features are well coordinated with temporal progression of mitosis consisting of five distinct stages (prophase, prometaphase, metaphase, anaphase and telophase), which are regulated by checkpoint mechanisms to maintain genomic integrity. Defects in chromosome segregation are linked to cancer and several genetic diseases. Some enzymes involved in chromosome regulation during cell division have become attractive drug targets.

Key Concepts:

Mitosis is the process of cell division that results in two genetically identical daughter cells.

Mitosis consists of five stages: prophase, prometaphase, metaphase, anaphase and telophase.

Chromosomes are classified according to centromere location as metacentric, submetacentric or acrocentric.

Chromosome movement in mitosis is a dynamic process controlled by microtubule dynamics and microtubule‐associated motor or nonmotor proteins.

Sister chromatid cohesion is established in S phase and is dissolved in two steps in vertebrate mitoses.

A kinetochore complex forms at the centromere in mitosis to allow microtubule capture.

Mitosis is a coordinated process regulated by checkpoint mechanisms to maintain genomic integrity.

Chromosomal missegregation results in cell death or aneuploidy.
Behavioural Phenotypes: Goals and Methods
Authors: Lloyd Elisabeth A , Valles Sean 
Published: November 2010

Abstract

The field of behavioural phenotypes involves the study of the cognitive and behavioural characteristics associated with genetic syndromes, leading to a fuller understanding of people with syndromes, and permits advances in knowledge regarding both atypical and typical human development. However, behavioural phenotypes offer a number of practical challenges. Behavioural phenotypes can be difficult to measure or even to define. Efforts to study gene–behaviour correlations require researchers to synthesise techniques and data from diverse fields, ranging from statistics to clinical diagnostics. In the course of behavioural phenotype studies researchers must also contend with pervasive biases emerging from ascertainment methods, choice of statistical cohorts or control groups, and so on. In addition to these difficulties, researchers also contend with bioethical difficulties arising from tasks such as studying cognitively impaired subjects.

Key Concepts:

Behavioural phenotypes are essential to the study of many genetic syndromes.

There is often a range of behavioural phenotypes associated with a genetic syndrome.

Behavioural phenotype studies have made important contributions to developmental biology.

Research into behavioural phenotypes involves a range of methodological challenges, especially the need for interdisciplinary collaboration.

Research into behavioural phenotypes introduces a wide variety of ethical challenges, as gene–behaviour associations can have social repercussions.
Androgen Insensitivity
Authors: Brinkmann Albert O 
Published: November 2010

Abstract

Androgen insensitivity is an X‐linked disorder of defective or absent virilisation in 46, XY individuals due to complete or partial resistance to androgens in androgen‐dependent tissues and organs. The syndrome is part of a scala of disorders of sex development (DSD). The molecular cause of the syndrome is mutations in the androgen receptor gene (locus: Xq11.2–12), resulting either in absence of an androgen receptor protein or in production of a mutant androgen receptor protein with partial or complete loss of its activity. Androgen insensitivity displays a broad phenotypic and genotypic spectrum. The phenotype can vary from a complete form (CAIS, complete androgen insensitivity syndrome), partial form (PAIS, partial androgen insensitivity syndrome) to a mild form (MAIS, mild androgen insensitivity syndrome). More than 400 different mutations in the androgen receptor gene have been reported. The majority of mutations are single‐base substitutions. However, deletions (1–6 base pairs), partial or complete gene deletions (>10 base pairs), insertions or duplications are also found. Mutations are compiled in the androgen receptor database (
www.mcgill.ca/androgendb
).

Key Concepts:

Androgens and the androgen receptor are indispensable for expression of the male phenotype.

The androgen receptor is a ligand‐dependent transcription factor and belongs to the family of nuclear receptors.

Despite two different ligands (testosterone and 5α‐dihydrotestosterone), only one androgen receptor cDNA has been identified and cloned.

A highly polymorphic (CAG)

n

‐CAA repeat, encoding a polyglutamine stretch, in exon 1 of the androgen receptor gene is used for identification of X‐chromosomes for carrier detection in pedigree analyses.

Variations in the polyglutamine stretch modulate androgen receptor transcriptional activity.

End‐organ resistance to androgens has been designated as androgen insensitivity syndrome (AIS) and is distinct from other XY disorders of sex development.

Defects in the androgen receptor gene can prevent normal development of both internal and external male structures in 46, XY individuals.

End‐organ resistance to androgens is X‐linked and only 46, XY individuals are affected.

AR gene mutations are transmitted in an X‐linked manner, but in 30% of the cases, mutations arise
de novo
.

Androgen insensitivity can be routinely analysed and differential diagnosis is possible with other syndromes presenting with almost similar phenotypes.
Crow, James
Authors: Plutynski Anya 
Published: November 2010

AbstractJames Crow has not only been a central figure in the history of twentieth century evolutionary genetics, but also has done a great deal of service for the sciences, as a teacher and mentor to some of the most influential biologists today, and as a leader in professional and public scientific societies. His research covered speciation, genetic load, the theory of random drift, the effects of inbreeding, the evolution of sex and effects of atomic radiation in human populations. Crow served as President of the Genetics Society of America and the American Society of Human Genetics, and is a member of the National Academy of Sciences, the National Academy of Medicine and the American Academy of Arts and Sciences. His work has shaped the thinking of generations of evolutionary biologists and geneticists.
Rhizobium
and Other
N
‐fixing Symbioses
Authors: Lindström Kristina , Mousavi Seyed Abdollah 
Published: November 2010

Abstract

Nitrogen‐fixing symbioses between bacteria and plants are major nitrogen contributors to the terrestrial biosphere. The

Rhizobium

–legume interaction is the best known and is agronomically the most important one. Several alpha‐ and betaproteobacterial species (rhizobia) can infect legume roots via root hair or crack invasion, preceded by signal exchange in the rhizosphere and followed by signal transduction in the root, resulting in the construction of a nitrogen‐fixing root nodule. Actinorhizal nodule formation by members of the actinobacterial genus

Frankia

follows the same pattern but is less known in detail. The nitrogen‐fixing root symbioses have the same evolutionary origin as mycorrhizal symbioses. Cyanobacterial nitrogen‐fixing symbioses are more diversified and formed mainly with representatives of genus

Nostoc

, and occur in diverse plant groups, the best known being

Azolla

,

Cycas

and

Gunnera

. Whole‐genome sequencing of the microbial symbionts has revealed interesting features related to the genetics of signalling, genome architecture and biogeography.

Key Concepts:

Symbiotic nitrogen fixation in plants contributes significantly to terrestrial ecosystems and sustainable agriculture.

Symbiotic nitrogen‐fixing interactions arose several times during evolution.

The
Rhizobium
–legume symbiosis serves as a model and paradigm for other symbiotic interactions between bacteria and plants.

Nitrogen‐fixing root symbioses have an origin common with mycorrhizal symbioses.

Most rhizobia have well‐conserved nodulation genes which encode signals, nodulation factors, which are perceived by the plant.

Cyanobacterial symbioses with plants are diversified, but involve mainly one microbial genus,
Nostoc
.
Origins of Human Aneuploidy
Authors: Delhanty Joy DA 
Published: November 2010

Abstract

At birth, at least 1% of humans have a clinically significant chromosomal abnormality. However, this represents a small fraction of those originally conceived since by the time of birth, natural selection has eliminated the vast majority of abnormal embryos and fetuses. This article describes the origin of these anomalies and their incidence at various stages of development.

There are three stages in development when aneuploidy may arise; during gamete formation, at fertilisation or during the early stages of embryo development. Gamete formation differs significantly between males and females, affecting the incidence of aneuploid gametes, which is 4‐fold higher in females than in males. Molecular cytogenetic techniques have revealed the extent of full and mosaic aneuploidy in embryos created by

in vitro

fertilisation (IVF), explaining the high level of arrested development affecting these embryos. Maternal age is the most significant factor affecting the incidence of aneuploidy but genetic anomalies in the parents are also important.

Key Concepts:

Chromosomally abnormal conceptions are very high in humans but the effects are lethal in almost all cases.

Aneuploidy may arise at three developmental stages; during gamete formation; at fertilisation or during embryogenesis.

Gamete formation (oogenesis or spermatogenesis) differs considerably between the sexes since males produce sperm throughout adult life whereas females are born with a finite set of oogonia.

These differences are reflected in the 4‐fold higher aneuploidy rate in females versus males.

Maternal age is the most significant factor affecting the incidence of aneuploidy but genetic variation in a parent is also an important factor.
The Winner's Curse
Authors: Nakaoka Hirofumi , Inoue Ituro 
Published: November 2010

Abstract

Winners in competitive bidding are losers in that they frequently pay too high a price. This phenomenon has recently been noted in genetic association studies of common diseases. The winner's curse in genetic association studies appears as upward bias in the estimated effect of a newly identified allele on disease risk when the study design lacks sufficient statistical power. The winner's curse manifests mostly in genome‐wide association (GWA) studies in which 300 000–1 000 000 single‐nucleotide polymorphisms are tested. The winner's curse also occurs in meta‐analysis of several GWA data sets. To counter this effect, construction of a large‐scale GWA study or a consortium‐based meta‐analysis of GWA studies that is sufficiently powered to account for the presence of between‐study heterogeneity is required.

Key Concepts:

‘Winner's curse’ is named for the phenomenon whereby winners at competitive auctions are likely to pay in excess of the value of the item.

Genetic association studies have been conducted to identify susceptibility genes underlying common diseases such as diabetes, schizophrenia and coronary artery disease. In genetic association studies, the winner's curse is the phenomenon whereby the disease risk of a newly identified genetic association is overestimated when the statistical power of original study is not sufficient.

The winner's curse implies that the sample size required for confirmatory study will be underestimated, resulting in failure of replication study to corroborate the association.

The winner's curse is common in genome‐wide association (GWA) studies because most single‐GWA studies are underpowered to detect small genetic effects at a stringent genome‐wide significance level.

In consortium‐based meta‐analyses of several GWA studies having high between‐study heterogeneity, there is an increased probability of the winner's curse.

In the discovery phase, construction of a larger scale GWA study or a consortium‐based meta‐analysis of GWA studies that evaluates between‐study heterogeneity is required to reduce probability of occurrence of the winner's curse.

In the replication phase, methodologies for reducing bias in the estimates of genetic effect are helpful to calculate the sample sizes required to replicate the discovered associations.
N‐Hydroxylamines for Peptide Synthesis
Authors: Subirós‐Funosas Ramon , Albericio Fernando , El‐Faham Ayman 
Published: November 2010

Abstractpeptide‐coupling reactions have significantly advanced in accord with the development of new N‐hydroxylamines as additives used in peptide synthsis, which has been covered in a number of valuable reviews. In this Chapter we focus on the development of theN‐hydroxylamines as additives for peptide synthesis, properties, synthesis, general comparison between differentN‐hydroxylamines, their uses in the synthesis of phosphonium, uronium/iminium salts , active esters, phosphate and sulfonate coupling reagents, polymer bondN‐hydroxylamines, as well as their applications in peptide synthesis.
Impact of hallux valgus severity on general and foot‐specific health‐related quality of life
Authors: Menz Hylton B. , Roddy Edward , Thomas Elaine , Croft Peter R. 
Published: November 2010

AbstractObjectiveTo explore the prevalence of and factors associated with hallux valgus and to assess the impact of hallux valgus severity on general and foot‐specific health‐related quality of life (HRQOL) in older people.MethodsPeople age ≥56 years who participated in the 6‐year followup of the North Staffordshire Osteoarthritis Project (n = 2,831) completed a survey that included the Medical Outcomes Study Short Form 36 (SF‐36) health survey and the Manchester Foot Pain and Disability Index (FPDI). Self‐reported hallux valgus severity was assessed using a validated instrument. Comparisons of SF‐36 and FPDI scores were made across 5 severity grades of hallux valgus.ResultsHallux valgus was present in 36.3% of the study population and was associated with female sex, older age, and pain in other bodily regions. There was a progressive reduction in all SF‐36 component scores as the severity of hallux valgus increased; this association remained after adjusting for age, sex, education, and body mass index. The strength of these associations diminished after also adjusting for pain in the back, hip, knee, and foot, but hallux valgus severity remained significantly associated with reduced physical function, bodily pain, general health, social function, and mental health subscale scores. Among participants with foot pain, increasing hallux valgus severity was also significantly associated with greater impairment on the pain and function subscales of the FPDI after adjusting for age, sex, and body mass index.ConclusionThere is a progressive reduction in both general and foot‐specific HRQOL with increasing severity of hallux valgus deformity.
Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide
Authors: Dall'Era Maria , Stone David , Levesque Victoria , Cisternas Miriam , Wofsy David 
Published: November 2010

AbstractObjectiveThere is a need to identify clinical characteristics and/or biomarkers that can predict treatment outcome in lupus nephritis. To this end, we utilized data from the Aspreva Lupus Management Study to identify possible baseline and early predictors of renal response to mycophenolate mofetil (MMF) or intravenous (IV) cyclophosphamide (CYC).MethodsPatients with class III–V lupus nephritis were randomized to MMF or IV CYC. We assessed predictors of renal response, including baseline demographic, clinical, laboratory, and histologic characteristics, as well as early clinical and laboratory data, obtained within the first 2 months of therapy. Odds ratios (ORs) and 95% confidence intervals for renal response were calculated for each putative predictor.ResultsNormalization of C3, C4, or both by week 8 was strongly predictive of renal response at week 24 (ORs 2.5, 2.6, and 2.9, respectively; P < 0.05). Reduction in proteinuria by ≥25% by week 8 was predictive of renal response at week 24 (OR 3.2, P < 0.05). Reduction in anti–double‐stranded DNA (anti‐dsDNA) by week 8 was not predictive of renal response. Only 3 baseline characteristics (C4 level, time since diagnosis of lupus nephritis, and estimated glomerular filtration rate [GFR]) were predictive of renal response; the remaining characteristics (age, age at lupus nephritis onset, time since diagnosis of systemic lupus erythematosus, sex, histopathologic class, anti‐dsDNA antibody level, C3 level, level of proteinuria, and use of angiotensin‐converting enzyme inhibitors, statins, or hydroxychloroquine) were not.ConclusionThis study demonstrates that baseline C4 level, time since diagnosis of lupus nephritis, baseline estimated GFR, early normalization of complement, and reduction in proteinuria independently predict renal response to therapy at 6 months.
Economic evaluation of multidisciplinary rehabilitation after primary total knee arthroplasty based on a randomized controlled trial
Authors: Kauppila Anna‐Maija , Sintonen Harri , Aronen Pasi , Ohtonen Pasi , Kyllönen Eero , Arokoski Jari P. A. 
Published: November 2010

AbstractObjectiveTo conduct an economic evaluation of a multidisciplinary, biopsychosocial outpatient rehabilitation program implemented 2–4 months after total knee arthroplasty (TKA), compared with conventional orthopedic care.MethodsAfter surgery, 86 patients were randomized to a multidisciplinary rehabilitation group (n = 44) or a conventional orthopedic care group (n = 42). Alongside the randomized controlled trial, we estimated the costs of rehabilitation, health care resource use, and community support. Information about resource use was collected by means of a questionnaire together with data from hospital records. The primary outcome (effectiveness) measure was change in self‐reported functional capacity and the secondary measure was quality‐adjusted life years (QALYs) gained during the 12‐month followup. Cost‐effectiveness was assessed from between‐group differences in costs, change in functional capacity, and QALYs gained.ResultsBoth protocols of providing rehabilitation services turned out to be equally effective, but the conventional orthopedic care protocol was unequivocally cost saving: the saving was €1,830 per patient (95% confidence interval −548, 3,623) using the available direct cost data.ConclusionMultidisciplinary rehabilitation for unselected osteoarthritis patients in the subacute period of recovery after TKA is not a cost‐effective use of health care resources. Similar rehabilitation protocols cannot be recommended for clinical pathways of TKA in the future.
Prevention of flare recurrences in childhood‐refractory chronic uveitis: An open‐label comparative study of adalimumab versus infliximab
Authors: Simonini Gabriele , Taddio Andrea , Cattalini Marco , Caputo Roberto , De Libero Cinzia , Naviglio Samuele , Bresci Cecilia , Lorusso Monica , Lepore Loredana , Cimaz Rolando 
Published: November 2010

AbstractObjectiveTo compare the efficacy and safety of adalimumab versus infliximab in an open‐label prospective, comparative, multicenter cohort study of childhood noninfectious chronic uveitis.MethodsThirty‐three patients (22 females, 11 males, median age 9.17 years) with refractory, vision‐threatening, noninfectious active uveitis were enrolled, and received for at least 1 year infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 6–8 weeks) or adalimumab (24 mg/m2 every 2 weeks). The primary outcome was to assess, once remission was achieved, the time of a first relapse. Time to remission, time to steroid discontinuation, and the number of relapses were also considered.ResultsSixteen children (12 with juvenile idiopathic arthritis [JIA], 3 with idiopathic uveitis, and 1 with Behçet's disease) were recruited in the adalimumab cohort and 17 children (10 with JIA, 5 with idiopathic uveitis, 1 with early‐onset sarcoidosis, and 1 with Behçet's disease) were recruited in the infliximab group. Cox regression analysis did not show statistically significant differences between the two groups with regard to time to achieve remission and time to steroid discontinuation, whereas a higher probability of uveitis remission on adalimumab during the time of treatment was shown (Mantel‐Cox χ2 = 6.83, P < 0.001). At 40 months of followup, 9 (60%) of 15 children receiving adalimumab compared to 3 (18.8%) of 16 children receiving infliximab were still in remission on therapy (P < 0.02).ConclusionEven if limited to a relatively small group, our study suggests that over 3 years of treatment, adalimumab is more efficacious than infliximab in maintaining remission of chronic childhood uveitis.
Pummelos as Concept Generators for Biomimetically Inspired Low Weight Structures with Excellent Damping Properties
Authors: Fischer Sebastian F. , Thielen Marc , Loprang Ruth R. , Seidel Robin , Fleck Claudia , Speck Thomas , Bührig‐Polaczek Andreas 
Published: November 2010

AbstractNatural materials often exhibit excellent mechanical properties. An example of outstanding impact resistance is the pummelo fruit (Citrus maxima) which can drop from heights of 10 m and more without showing significant outer damage. Our data suggest that this impact resistance is due to the hierarchical organization of the fruit peel, called pericarp. The project presented in the current paper aims at transferring structural features from the pummelo pericarp to engineering materials, in our case metal foams, produced by the investment casting process. The transfer necessitates a detailed structural and mechanical analysis of the biological model on the one hand, and the identification and development of adequate materials and processes on the other hand. Based on this analysis, engineering composite foam structures are developed and processed which show enhanced damping and impact properties. The modified investment casting process and the model alloy Bi57Sn43 proved to be excellent candidates to make these bio‐inspired structures. Mechanical testing of both the natural and the engineering structures has to consider the necessity to evaluate the impact of the different hierarchical features. Therefore, specimens of largely varying sizes have to be tested and size effects cannot be ignored, especially as the engineering structures might be upscaled in comparison with the natural role model. All in all, the present results are very promising: the basis for a transfer of bio‐inspired structural hierarchical levels has been set.