bluuebunny/crossref_metadata_2025 huggingface dataset:
Root Nodules (Legume–RhizobiumSymbiosis)
Authors: Brewin Nicholas J
Published: November 2010

Root nodule symbiosis enables nitrogen‐fixing bacteria to convert atmospheric nitrogen into a form that is directly available for plant growth. Biological nitrogen fixation provides a built‐in supply of nitrogen fertiliser for many legume crops such as peas, beans and clover. Legumes (Fabales) interact with single‐celled Gram‐negative bacteria, collectively termed rhizobia, whereas members of three other Rosid orders (Fagales, Cucurbitales and Rosales) interact with Gram‐positive filamentous actinobacteria of the genusFrankia. In legumes, infection proceeds through intercellular and trans‐cellular channels termed infection threads. At the same time, cells in the root cortex are induced to divide and generate the tissues of the nodule. Nitrogen fixation normally takes place within specialised bacteroid cells enclosed within organelle‐like cytoplasmic compartments termed symbiosomes. The anatomy and physiology of root nodules both reflect a high degree of structural and metabolic integration between plant and microbial symbionts.

Key Concepts:

Legumes (family Fabales) develop root nodules that harbourRhizobiumbacteria (rhizobia).

Endosymbiotic bacteria (bacteroids) convert nitrogen to ammonia (biological nitrogen fixation).

Legume crops restore fertility to agricultural soils by capturing nitrogen from the atmosphere.

The legume–Rhizobiumsymbiosis provides one‐fifth of all nitrogen inputs into global agriculture.

Symbiosis is based on metabolic exchange for mutual benefit: exchanges of oxygen, carbon and nitrogen are tightly regulated.

Legumes only form a nitrogen‐fixing symbiosis with single‐celled bacteria collectively termedRhizobium. However, other (related) groups of flowering plants form a root nodule symbiosis with filamentous actinobacteria of the genusFrankia.

Some of the invasion processes adopted byRhizobiumandFrankiaare shared with a mineral‐scavenging symbiosis involving arbuscular mycorrhizal fungi that originated over 400 Ma.

Colonisation of host cells byRhizobiumusually involves specialised invasion structures termed ‘infection threads’ and specialised organelle‐like compartments termed ‘symbiosomes’.

During evolution, there has been horizontal transfer of the genes that specify the capability for nodulation and symbiotic nitrogen fixation between diverse groups of soil bacteria.
Pseudogenes and Their Evolution
Authors: Podlaha Ondrej , Zhang Jianzhi
Published: November 2010

Pseudogenes are relics of former genes that no longer possess biological functions. They are abundant in the genomes of complex organisms such as vertebrates and flowering plants and provide a useful resource for studying mutation rates and neutral evolutionary patterns. Processed pseudogenes can be regarded as fossilised footprints of past gene expression, permitting a peek into ancient transcriptomes. Occasionally adaptive, pseudogenisation is usually a neutral process. Yet, it can have a substantial impact on future evolution by limiting or opening certain evolutionary possibilities. Studies of pseudogenisation may help date key phenotypic changes in evolution and understand the genetic basis of phenotypic evolution. Recent studies found some pseudogenes to possess apparent functions in gene regulation, creating a difficulty in defining pseudogenes.

Key Concepts:

Pseudogenes are relatives of functional genes that have lost their functions.

Most pseudogenes arise from degenerated replicates of functional genes produced by either DNA‐mediated gene duplication or RNA‐mediated retroposition.

Processed pseudogenes arise from retroposition and their copy numbers are positively correlated with the germline expression levels of their parent genes. Thus, they may be regarded as fossilised footprints of past gene expression for studying ancient transcriptomes.

Most pseudogenes evolve neutrally and thus have been used to study the rates and patterns of mutations.

The human and mouse genomes contain nearly as many pseudogenes as functional genes.

The number of pseudogenes in a genome, compared to that of functional genes, varies substantially among organisms.

Pseudogenisation is usually a neutral process; yet, it can have significant impacts on future evolution by either limiting or opening certain evolutionary possibilities.

Pseudogenisation may occasionally be adaptive when the expression of a gene becomes deleterious, due to changes of the genetic background or environment.

Some apparent pseudogenes have been found to possess regulatory functions, causing a difficulty in defining pseudogenes.
DNA
Profiling in Ecology
Authors: Hamilton Matthew J , Sadowsky Michael J
Published: November 2010

Deoxyribonucleic acid
(DNA) profiling uses various molecular biological techniques to identify, classify, and study the ecology and evolution of organisms based on differences in DNA sequence. These differences in DNA sequence are known as polymorphisms, which may be as simple as a single nucleotide at a given nucleotide position within the genome or as complex as variant numbers of tandem repeat sequences or the presence of an interspersed repetitive element. Individuals, populations or species‐specific DNA polymorphisms are used as targets to generate fingerprint patterns suitable for the differentiation of individuals and populations. Data generated by DNA profiling methods are used to provide quantitative or qualitative information for population genetics, human diseases, diversity, phylogeny, epidemiological, forensics and conservation management purposes.

Key Concepts:

DNA profiling methodologies allow for the classification of organisms based on polymorphisms in DNA sequences at a given loci.

DNA profiling methods that can be used to detect single nucleotide and repetitive element polymorphisms include: amplified and restriction fragment length polymorphisms (AFLP/RFLP), multilocus fingerprinting using hybridisation, random amplified polymorphic DNA and denaturing gradient and pulse field gel electrophoresis (DGGE/PFGE).

DNA profiling patterns can be used to identify individuals, determine kinship and genealogy, examine inbreeding, and bottlenecks and differentiate populations.
Chromosomes during Cell Division
Authors: Liu Song‐Tao , Allison David C , Nestor‐Kalinoski Andrea L
Published: November 2010

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

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

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

James 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

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

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

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

peptide‐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

Objective

To 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.

Methods

People 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.

Results

Hallux 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.

Conclusion

There 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

Objective

There 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).

Methods

Patients 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.

Results

Normalization 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.

Conclusion

This 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

Objective

To 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.

Methods

After 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.

Results

Both 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.

Conclusion

Multidisciplinary 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

Objective

To compare the efficacy and safety of adalimumab versus infliximab in an open‐label prospective, comparative, multicenter cohort study of childhood noninfectious chronic uveitis.

Methods

Thirty‐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.

Results

Sixteen 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).

Conclusion

Even 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

Natural 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.
Site‐Selectively Coated, Densely‐Packed Microprojection Array Patches for Targeted Delivery of Vaccines to Skin
Authors: Chen Xianfeng , Corbett Holly J. , Yukiko Sally R. , Raphael Anthony P. , Fairmaid Emily J. , Prow Tarl W. , Brown Lorena E. , Fernando Germain J. P. , Kendall Mark A. F.
Published: November 2010

Densely packed dry‐coated microprojections are shown to deliver vaccines to targeted locations within the skin that are rich in immune cells, thus inducing protective immune responses against a lethal virus challenge. Selectively limiting the antigen coating to the tips of the projections, which penetrate the skin, would significantly reduce the amount of vaccine required in immunization. In this paper a simple technique, dip‐coating the microprojections, is introduced to meet this goal. By increasing the coating solution viscosity, an otherwise strong capillary action is mitigated and the desired controlled coating length on projections is achieved. Following application to the skin, most of the coated vaccine material is rapidly released from the projections (82.6% in mass within 2 min) to the target locations within the skin strata and a potent immune response is induced when a conventional influenza vaccine (Fluvax) is tested in a mouse model. The utility of this coating approach to a variety of molecules representative of vaccines (e.g., chicken egg ovalbumin (OVA) protein, DNA, and fluorescent dyes) is demonstrated. These collective attributes, together with the simplicity of the approach, position the dip‐coating method for practical utility in large vaccination campaigns.
Air/Liquid‐Pressure and Heartbeat‐Driven Flexible Fiber Nanogenerators as a Micro/Nano‐Power Source or Diagnostic Sensor
Authors: Li Zetang , Wang Zhong Lin
Published: November 2010

We present a new approach for fabricating flexible fiber nanogenerators (FNGs) that can be used for smart shirts, flexible electronics, and medical applications. These FNGs are based on carbon fibers that are covered cylindrically by textured zinc oxide (ZnO) thin films. Once subjected to uni‐compression by applying a pressure, the cylindrical ZnO thin film is under a compressive strain, resulting in a macroscopic piezopotential across its inner and exterior surfaces owing to the textured structure of the film, which is the driving force for generating an electric current in the external load. Using such a structure, an output peak voltage of 3.2 V and average current density of 0.15 μA cm−2 are demonstrated. The FNGs rely on air pressure, so that it can work in a non‐contact mode in cases of rotating tires, flowing air/liquid, and even in blood vessels. Pressure‐driven FNGs added to a syringe show potential to harvest energy in blood vessels, gas pipes, and oil pipes, as long as there is a fluctuation in pressure (or turbulence). Heart‐pulse driven FNGs can serve as ultrasensitive sensors for monitoring the behavior of the human heart, which may possibly be applied to medical diagnostics as sensors and measurement tools.
Thermoregulated ligand–palladium‐catalyzed Suzuki reaction in water
Authors: Liu Ning , Liu Chun , Yan Bo , Jin Zilin
Published: November 2010

An efficient and recyclable protocol for the Suzuki reaction in water has been developed based on the cloud point of thermoregulated ligand Ph2P(CH2CH2O)nCH3 (n = 22). This method allows the preparation of a variety of biaryls in high yields and the catalytic system can be recycled four times with high efficiency. Copyright © 2010 John Wiley & Sons, Ltd.
Comparative study on the molecular and electronic structure of MgCl2· 6 NH3 and MgCl2· 6H2O
Authors: Song Xingfu , Liu Gousheng , Sun Ze , Yu Jianguo
Published: November 2010

Anhydrous magnesium chloride is the preferred raw material for electrolytic production of magnesium metal; however, it is not possible to fully dehydrate magnesium chloride by heating in air because of hydrolytic decomposition. The dehydration should be carried out in hydrogen chloride gas atmosphere, or by a process where the intermediate hexammoniate magnesium chloride (MgCl2·6 NH3) is calcined at high temperature to remove the six crystal ammonia. The most popular process to prepare MgCl2·6 NH3 is an organic solvent process which is energy efficient and exhibits good quality control. Recently, we prepared high‐purity anhydrous MgCl2 by a coupling reactive crystallization (CRC) process. In this study, quantum chemistry calculations based on the method of density functional theory (DFT) were used to determine the molecular and electronic structure of MgCl2·6 NH3 and MgCl2·6H2O at the levels of B3LYP/6‐31G* and B3LYP/6‐311G*, respectively. These results were compared with available experimental results. The DFT results show that for model MgCl2·6H2O, the bond lengths of R[OMg] and O atom Mulliken charges can be classified into three levels, each level has two crystals of water. As a result, the six crystal water will be removed by three steps, two crystals of water in each step. However, for model MgCl2·6 NH3, the bond lengths of R[NMg] and N atom Mulliken charges are classified into two levels, four crystal ammonia will be removed in the first step and two crystal ammonia will be removed in the second step. The calculations are verified by TG and DTA data from the literature and by our experiments. This study is significant for better understanding the thermal decomposition mechanism and laboratory preparation of MgCl2·6 NH3 and anhydrous MgCl2. Copyright © 2010 Curtin University of Technology and John Wiley & Sons, Ltd.
Systemic lupus erythematosus serum deposits C4d on red blood cells, decreases red blood cell membrane deformability, and promotes nitric oxide production
Authors: Ghiran Ionita C. , Zeidel Mark L. , Shevkoplyas Sergey S. , Burns Jennie M. , Tsokos George C. , Kyttaris Vasileios C.
Published: November 2010

Objective

Systemic lupus erythematosus (SLE) is characterized by intravascular activation of the complement system and deposition of complement fragments (C3 and C4) on plasma membranes of circulating cells, including red blood cells (RBCs). The aim of this study was to address whether this process affects the biophysical properties of RBCs.

Methods

Serum and RBCs were isolated from patients with SLE and healthy controls. RBCs from healthy universal donors (type O, Rh negative) were incubated with SLE or control serum. We used flow cytometry to assess complement fragment deposition on RBCs. RBC membrane deformability was measured using 2‐dimensional microchannel arrays. Protein phosphorylation levels were quantified by Western blotting.

Results

Incubation of healthy universal donor RBCs with sera from patients with SLE, but not with control sera, led to deposition of C4d fragments on the RBCs. Complement‐decorated RBCs exhibited significant decreases in both membrane deformability and flickering. Sera from SLE patients triggered a transitory Ca++ influx in RBCs that was associated with decreased phosphorylation of β‐spectrin and with increased phosphorylation of band 3, two key proteins of RBC cytoskeleton. Finally, incubation with SLE sera led to the production of nitric oxide by RBCs, whereas this did not occur with control sera.

Conclusion

Our data suggest that complement activation in patients with SLE leads to calcium‐dependent cytosketeletal changes in RBCs that render them less deformable, probably impairing their flow through capillaries. This phenomenon may negatively affect the delivery of oxygen to the tissues.
The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case–control samples
Authors: Rodríguez‐Rodríguez Luis , Taib Wan Rohani Wan , Topless Ruth , Steer Sophia , González‐Escribano María F. , Balsa Alejandro , Pascual‐Salcedo Dora , González‐Gay Miguel A. , Raya Enrique , Fernandez‐Gutierrez Benjamín , González‐Álvaro Isidoro , Bottini Nunzio , Witte Torsten , Viken Marte K. , Coenen Marieke J. H. , van Riel Piet L. C. M. , Franke Barbara , den Heijer Martin , Radstake Timothy R. D. J. , Wordsworth Paul , Lie Benedicte A. , Merriman Tony R. , Martín Javier
Published: November 2010

Objective

Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA).

Methods

RA patients (n = 5,579) were recruited from outpatient clinics from 6 different countries (Spain, New Zealand, the UK, Norway, The Netherlands, and Germany). Healthy controls (n = 5,392) were recruited from the same areas. There was 100% power to detect an effect equivalent to that observed in SLE. Samples were genotyped for the PTPN22 R263Q (rs33996649) and PTPN22 R620W (rs2476601) polymorphisms using a TaqMan 5′‐allele discrimination assay. The effect of the R263Q variant was analyzed in isolation and in combination with the effect of R620W, using Unphased and Stata 10 software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined.

Results

The minor allele A of PTPN22 R263Q was significantly associated with a lower risk of RA in the pooled analysis of the 6 populations (P = 0.016, Mantel‐Haenszel pooled OR 0.80 [95% CI 0.67–0.96]), independent of the effect of the R620W polymorphism. Both polymorphisms had an additive effect. The more RA risk alleles carried (R263Q G allele, R620W T allele), the higher the RA risk (for 2 versus 1 risk allele P = 0.014, OR 1.28 [95% CI 1.05–1.55], for 3 versus 1 risk allele P = 6.67 × 10−11, OR 2.01 [1.63–2.48], and for 4 versus 1 risk allele P = 6.50 × 10−11, OR 3.55 [2.42–5.20]).

Conclusion

Our findings indicate that the minor allele of the PTPN22 R263Q polymorphism is associated with a lower risk of RA. This association is independent of the well‐established association between PTPN22 R620W and RA. Both polymorphisms have an additive effect on the risk of RA.
Octacalcium phosphate crystals induce inflammation in vivo through interleukin‐1 but independent of the NLRP3 inflammasome in mice
Authors: Narayan Sharmal , Pazar Borbola , Ea Hang‐Korng , Kolly Laeticia , Bagnoud Nathaliane , Chobaz Véronique , Lioté Frédéric , Vogl Thomas , Holzinger Dirk , Kai‐Lik So Alexander , Busso Nathalie
Published: November 2010

Objective

To determine the mechanisms involved in inflammatory responses to octacalcium phosphate (OCP) crystals in vivo.

Methods

OCP crystal–induced inflammation was monitored using a peritoneal model of inflammation in mice with different deficiencies affecting interleukin‐1 (IL‐1) secretion (IL‐1α–/–, IL‐1β–/–, ASC–/–, and NLRP3–/–mice) or in mice pretreated with IL‐1 inhibitors (anakinra [recombinant IL‐1 receptor antagonist] and anti–IL‐1β). The production of IL‐1α, IL‐1β, and myeloid‐related protein 8 (MRP‐8)–MRP‐14 complex was determined by enzyme‐linked immunosorbent assay. Peritoneal neutrophil recruitment and cell viability were determined by flow cytometry. Depletion of mast cells or resident macrophages was performed by pretreatment with compound 48/80 or clodronate liposomes, respectively.

Results

OCP crystals induced peritoneal inflammation, as demonstrated by neutrophil recruitment and up‐modulation of IL‐1α, IL‐1β, and MRP‐8–MRP‐14 complex, to levels comparable with those induced by monosodium urate monohydrate crystals. This OCP crystal–induced inflammation was both IL‐1α– and IL‐1β–dependent, as shown by the inhibitory effects of anakinra and anti–IL‐1β antibody treatment. Accordingly, OCP crystal stimulation resulted in milder inflammation in IL‐1α–/–and IL‐1β–/–mice. Interestingly, ASC–/–and NLRP3–/–mice did not show any alteration in their inflammation status in response to OCP crystals. Depletion of the resident macrophage population resulted in a significant decrease in crystal‐induced neutrophil infiltration and proinflammatory cytokine production in vivo, whereas mast cell depletion had no effect. Finally, OCP crystals induced apoptosis/necrosis of peritoneal cells in vivo.

Conclusion

These data indicate that macrophages, rather than mast cells, are important for initiating and driving OCP crystal–induced inflammation. Additionally, OCP crystals induce IL‐1–dependent peritoneal inflammation without requiring the NLRP3 inflammasome.
Precision Synthesis of Hybrid Block Copolymers by Organotellurium‐Mediated Successive Living Radical and Cationic Polymerizations
Authors: Mishima Eri , Yamada Takeshi , Watanabe Hiroshi , Yamago Shigeru
Published: November 2010

Living cationic polymerization reactions using organotellurium compounds as initiators are reported. Polymerization of vinyl ethers in the presence of an organotellurium initiator and a Lewis acid, such as In(OTf)3and BF3⋅OEt2, affords well‐controlled poly(vinyl ether)s with predetermined molecular weights and narrow molecular‐weight distributions. Poly(meth)acrylates possessing organotellurium group at the ω‐polymer end, which are prepared using organotellurium‐mediated controlled/living radical polymerization (TERP), are used as macroinitiators for living cationic polymerization. The one‐pot, two‐step reaction of the macroinitiator with vinyl ether under radical and cationic conditions gives well‐controlled AB diblock copolymers. ABA triblock copolymers with controlled structures are also synthesized from a bifunctional organotellurium initiator.
Solid‐phase Total Synthesis of (−)‐Apratoxin A and Its Analogues and Their Biological Evaluation
Authors: Doi Takayuki , Numajiri Yoshitaka , Takahashi Takashi , Takagi Motoki , Shin‐ya Kazuo
Published: November 2010

Two approaches for the solid‐phase total synthesis of apratoxin A and its derivatives were accomplished. In synthetic route A, the peptide was prepared by the sequential coupling of the corresponding amino acids on trityl chloride SynPhase Lanterns. After cleavage from the polymer‐support, macrolactamization of 10, followed by thiazoline formation, provided apratoxin A. This approach, however, resulted in low yield because the chemoselectivity was not sufficient for the formation of the thiazoline ring though its analogue 33 was obtained. However, in synthetic route B, a cyclization precursor was prepared by solid‐phase peptide synthesis by using amino acids 13–15 and 18. The final macrolactamization was performed in solution to provide apratoxin A in high overall yield. This method was then successfully applied to the synthesis of apratoxin analogues. The cytotoxic activity of the synthetic derivatives was then evaluated. The epimer 34 was as potent as apratoxin A, and O‐methyl tyrosine can be replaced by 7‐azidoheptyl tyrosine without loss of activity. The 1,3‐dipolar cycloaddition of 38 with phenylacetylene was performed in the presence of a copper catalyst without affecting the thiazoline ring.
Nonsyndromic cleft lip and palate: CRISPLD genes and the folate gene pathway connection
Authors: Chiquet Brett T. , Henry Robin , Burt Amber , Mulliken John B. , Stal Samuel , Blanton Susan H. , Hecht Jacqueline T.
Published: November 2010

BACKGROUND

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect that has a multifactorial etiology. Despite having substantial genetic liability, <15% of the genetic contribution to NSCLP has been delineated. In our efforts to dissect the genetics of NSCLP, we found that variation in the CRISPLD2 (cysteine‐rich secretory protein LCCL domain containing 2) gene is associated with NSCLP and that the protein is expressed in the developing murine craniofacies. In addition, we found suggestive linkage of NSCLP (LOD > 1.0) to the chromosomal region on 8q13.2–21.13 that contains the CRISPLD1 gene. The protein products of both CRISPLD1 and CRISPLD2 contain more cysteine residues than comparably sized proteins. Interestingly, the folic acid pathway produces endogenous cysteines, and variation in genes in this pathway is associated with NSCLP. Based on these observations, we hypothesized that variation in CRISPLD1 contributes to NSCLP and that both CRISPLD genes interact with each other and genes in the folic acid pathway.

METHODS

Single nucleotide polymorphisms (SNPs) in CRISPLD1 were genotyped in our non‐Hispanic white and Hispanic multiplex and simplex NSCLP families.

RESULTS

There was little evidence for a role of variation for CRISPLD1 alone in NSCLP. However, interactions were detected between CRISPLD1/CRISPLD2 SNPs and variation in folate pathway genes. Altered transmission of one CRISPLD1 SNP was detected in the NHW simplex families. Importantly, interactions were detected between SNPs in CRISPLD1 and CRISPLD2 (15 interactions, 0.0031 ≤p < 0.05).

CONCLUSION

These novel findings suggest that CRISPLD1 plays a role in NSCLP through the interaction with CRISPLD2 and folate pathway genes. Birth Defects Research (Part A), 2011. © 2010 Wiley‐Liss, Inc.
Maternal smoking, passive tobacco smoke, and neural tube defects
Authors: Suarez Lucina , Ramadhani Tunu , Felkner Marilyn , Canfield Mark A. , Brender Jean D. , Romitti Paul A. , Sun Lixian
Published: November 2010

BACKGROUND

Although cigarette smoke is a well‐established toxin and harmful to the developing embryo, the evidence for an independent effect on the occurrence of neural tube defects (NTDs) is mixed. In this study, we examined the relation between NTDs and maternal exposures to cigarette smoke, including passive smoke exposure.

METHODS

We used cases and controls from the large, multistate, population‐based National Birth Defects Prevention Study. A total of 1041 NTD cases and 5862 live birth controls, delivered during 1997 to 2004, were available for analyses. Mothers were interviewed by telephone between 6 weeks and 24 months after delivery. Participation rates were 71% for NTD case mothers and 69% for control mothers.

RESULTS

Compared with nonsmokers (and also not exposed to passive cigarette smoke), mothers exposed only to passive smoke had an increased NTD odds ratio (OR, 1.7; 95% confidence interval [CI], 1.4–2.0), adjusted for race–ethnicity, and study center. There was no increased OR for mothers who actively smoked 24 or fewer cigarettes per day. Mothers who smoked 25 or more cigarettes per day had an elevated OR (OR, 1.6; 95% CI, 0.9–3.0), but the OR adjusted for race–ethnicity, and center was compatible with the null.

CONCLUSION

Results suggest that maternal exposure to passive smoke is associated with NTDs. Women who plan on becoming pregnant should minimize their exposure to passive smoke and refrain from smoking. Birth Defects Research (Part A), 2011. © 2010 Wiley‐Liss, Inc.