bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic dilatation in Cockayne syndrome
Authors: Ovaert Caroline , Cano Aline , Chabrol Brigitte
Published: October 2007

Cockayne syndrome is a rare growth failure and premature aging disorder featuring abnormal ultraviolet sensitivity and impaired transcription‐coupled DNA repair. Cardiac involvement has not been described in Cockayne patients except for one recently described case of dilated cardiomyopathy. We describe one patient in whom marked ascending aorta dilatation was observed together with mild aortic regurgitation. Ascending aorta dilatation might be another feature of premature aging in Cockayne syndrome and may require cardiovascular investigation and monitoring. © 2007 Wiley‐Liss, Inc.
Syndrome of congenital cataracts, sensorineural deafness, Down syndrome‐like facial appearance, short stature, and mental retardation: Two additional cases
Authors: Keppler‐Noreuil Kim , Welch Judy , Baker‐Lange Katherine
Published: October 2007

An apparently new syndrome of congenital cataracts, sensorineural deafness, Down syndrome‐like facial appearance, short stature, and mental retardation was described by Gripp et al.1996. The authors reported on two unrelated patients with congenital cataracts, sensorineural deafness, distinctive facial appearance, mental retardation, postnatal short stature, and skeletal changes. We report on two additional patients with findings most similar to the reported patients by Gripp et al.1996, including bilateral congenital cataracts, hearing loss, craniofacial abnormalities, short stature, skeletal abnormalities, and developmental delay. Both of the patients reported herein had chromosome microarray analysis, which showed normal results in Patient 2 but abnormal results in Patient 1 and his mother who both had a chromosome 11q25 subtelomere deletion. Patient 1 and his mother's findings are atypical for the common findings reported in Jacobsen syndrome (11q terminal deletion syndrome), and consistent with the patients reported by Gripp et al.1996. The etiology for these cases has been unknown. The microarray results on Patient 1 suggest that the other patients with findings of developmental delay, short stature, congenital cataracts, sensorineural hearing loss, and similar craniofacial features may have either a microdeletion of chromosome 11q terminal region or haploinsufficiency of a gene localized to this region. © 2007 Wiley‐Liss, Inc.
LEOPARD syndrome with partly normal skin and sex chromosome mosaicism
Authors: Writzl Karin , Hoovers Jan , Sistermans Erik A. , Hennekam Raoul C.M.
Published: October 2007

We report on a family with LEOPARD syndrome which was molecularly proven (p.Thr468Met in PTPN11) in a father and his adult son. The father had multiple lentigines dispersed equally over his body; the son was similarly affected except for the left part of thorax, back and left arm, which were completely devoid of lentigines and only showed a few nevi. In addition, the son was found to have a mosaic karyotype, 47,XYY/46,XY, in lymphocytes. Skin biopsies from the pigmented and unpigmented forearm showed that mainly a 47,XYY karyotype was present in the pigmented skin and mainly a 46,XY karyotype in the unpigmented skin. In both fibroblast cultures the PTPN11 mutation was present, and no additional mutation could be detected. We discuss the various possible explanations for this phenotype, which include the possibility of coincidence; revertant mosaicism; silencing of a second PTPN11 mutation; gene(s) located on a sex chromosome influencing the phenotype; and epigenetic influences. We favor that the co‐occurrence of a sex chromosome mosaicism and mosaicism for skin symptoms in a single patient with LEOPARD syndrome is coincidence, but that mosaicism for LEOPARD skin symptoms in itself may well be more frequent and needs additional studies. Each of the above‐hypothesized mechanisms may then remain possible. © 2007 Wiley‐Liss, Inc.
Molecular characterization of a novel X‐linked syndrome involving developmental delay and deafness
Authors: Hildebrand Michael S. , de Silva Michelle G. , Tan Tiong Yang , Rose Elizabeth , Nishimura Carla , Tolmachova Tanya , Hulett Joanne M. , White Susan M. , Silver Jeremy , Bahlo Melanie , Smith Richard J.H. , Dahl Hans‐Henrik M.
Published: October 2007

X‐linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr‐Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X‐linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X‐linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X‐chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3–q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP‐1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP‐1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP‐1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. © 2007 Wiley‐Liss, Inc.
Complete sex reversal in a WAGR syndrome patient
Authors: Le Caignec Cedric , Delnatte Capucine , Vermeesch Joris R. , Boceno Michelle , Joubert Madeleine , Lavenant Francoise , David Albert , Rival Jean‐Marie
Published: October 2007

The WAGR contiguous gene deletion syndrome is a combination of Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation. Children with WAGR syndrome invariably have a constitutional chromosomal deletion at 11p13. WT1 haploinsufficiency is associated with a significant risk of Wilms tumor while PAX6 haploinsufficiency lead to aniridia, both genes located in the deleted region. The 46,XY patients with WAGR syndrome are often born with genital abnormalities such as cryptorchidism or hypospadias but more rarely ambiguous genitalia. To our knowledge, complete sex reversal has never been observed in WAGR syndrome patients. Here, we report on the clinical, cytogenetic, and molecular characterization of a child with WAGR syndrome and complete sex reversal. The young girl had female external and internal genitalia with normal uterus and fallopian tubes while the ovaries were not observed. Chromosomal analysis showed a 46,XY,del(11)(p12p14.1) karyotype. A 1‐Mb resolution array CGH experiment estimated the size of the interstitial deletion at ≈10 Mb encompassing WT1 and PAX6. The entire coding regions of WT1 and SRY have been sequenced and no mutation has been identified. Frasier syndrome (FS) and Denys‐Drash syndrome (DDS) are two disorders associated with mutations in the WT1 gene. Complete sex reversal is a feature usually present in FS and sometimes in DDS, but until now never observed in WAGR syndrome. The present report suggests that these conditions may be considered as part of the spectrum of disease due to WT1 gene alterations. © 2007 Wiley‐Liss, Inc.
Third case of paternal isodisomy for chromosome 7 with cystic fibrosis: A new patient presenting with normal growth
Authors: Le Caignec Cedric , Isidor Bertrand , de Pontbriand Ulrika , David Valerie , Audrezet Marie‐Pierre , Ferec Claude , David Albert
Published: October 2007

Many patients with maternal uniparental disomy of chromosome 7 (UPD7) have been described, mainly with intrauterine and postnatal growth retardation or with Silver–Russell syndrome. In contrast, only three cases of paternal UPD7 have been reported, all associated with recessive disorders. Here, we report on the clinical and molecular data of the third patient with paternal UPD7 and cystic fibrosis. Pre‐ and postnatal growth were normal. These findings support the hypothesis that paternal isodisomy for human chromosome 7 may have no phenotypic effect on growth. © 2007 Wiley‐Liss, Inc.
Variation of the degree of sacral vertebral body fusion in adulthood in two European modern skeletal collections
Authors: Belcastro Maria Giovanna , Rastelli Elisa , Mariotti Valentina
Published: October 2007

A new standardized scoring method was used to study age variation of the degree of fusion of the ventral face of the sacral vertebral bodies (SVF) in 904 adult skeletons of both sexes from two identified modern samples (20th c.): Frassetto collections (Museum of Anthropology, University of Bologna, Italy) and Colecção de Esqueletos Identificados (Museum of Anthropology, University of Coimbra, Portugal). SVF was scored for each fusion site (between S1 and S2, etc.) on a four‐stage scale, from nonfusion (Degree 0) to complete fusion (Degree 3). Inter‐observer error of 1.2% suggested good reproducibility. The data were analyzed according to age, sex, and population. There were sex and population differences only in young adults (20–34 years). Sex differences in SVF were present in both collections, with females displaying earlier fusion than males. The differences occurred until 35 years, after which there was a generalized prevalence of completely fused sacra. Population differences were observed for males, with the Sassari men showing later sacral vertebral fusion than the Coimbra men. Our study suggests that incompletely fused sacra can help in distinguishing young adults from old adults regardless of sex and population. Am J Phys Anthropol 135:149–160, 2008. © 2007 Wiley‐Liss, Inc.
Getting the best possible deal by helping—not pleasing—the neutral
Authors: Goldberg Stephen B.
Published: October 2007

There's more that parties can do to help themselves in mediation. Veteran Evanston, Ill., neutral Stephen B. Goldberg describes how parties can work more effectively with the neutrals they hire to help them close cases and deals
Bildung von Peptidfibrillen
Authors: Hamley Ian W.
Published: October 2007

Die Bildung von Peptidfibrillen spielt eine bedeutende Rolle bei vielen Krankheiten, die durch Amyloidablagerungen verursacht werden. Intensiv erforscht wird die Bildung von Fibrillen aber auch wegen ihres großen Anwendungspotenzials in der Bionanotechnologie, wo Hydrogele aus Peptidfibrillen als Zellgerüste und als Substrate für funktionelle und responsive Biomaterialien, Biosensoren und Nanodrähte Anwendung finden können. In diesem Aufsatz werden die grundlegenden Aspekte der Selbstorganisation von Peptiden zu Fibrillen behandelt. Sowohl natürliche amyloidbildende Peptide als auch synthetische Verbindungen, z. B. Peptidfragmente, Copolymere und Amphiphile, werden diskutiert.
Organic Transformations on σ‐Aryl Organometallic Complexes
Authors: Gagliardo Marcella , Snelders Dennis J. M. , Chase Preston A. , Klein Gebbink Robertus J. M. , van Klink Gerard P. M. , van Koten Gerard
Published: October 2007

This work reviews recent developments in the field of organic transformations on σ‐aryl organometallic complexes. The general notion that MC σ bonds are kinetically labile, highly reactive, and incompatible with typical reaction conditions met in organic synthesis has limited the use of these synthetic strategies thus far. However, organic transformations on metal‐bound σ‐aryl fragments are being used more and more by chemists in both industry and academia. In this Review, emphasis is put on the synthetic methods applied in this field up to now. The simplicity and generally good yields of these methods are very attractive for the construction of functionalized organometallic building blocks that are potentially useful as photochemical molecular devices, biosensors and ‐conjugates, or molecular switches. Thus, this Review has been tailored for a broader audience with the aim of encouraging the application of these strategies.
Peptide Fibrillization
Authors: Hamley Ian W.
Published: October 2007

The fibrillization of peptides is relevant to many diseases based on the deposition of amyloids. The formation of fibrils is being intensively studied, especially in terms of nanotechnology applications, where fibrillar peptide hydrogels are used for cell scaffolds, as supports for functional and responsive biomaterials, biosensors, and nanowires. This Review is concerned with fundamental aspects of the self‐assembly of peptides into fibrils, and discusses both natural amyloid‐forming peptides and synthetic materials, including peptide fragments, copolymers, and amphiphiles.
Influence of post‐treatments on the properties of porous poly(vinyl alcohol) membranes
Authors: Wang Yan‐Li , Yang Hu , Xu Zhen‐Liang
Published: October 2007

Porous poly(vinyl alcohol) (PVA) membranes were prepared by a phase‐inversion method. The influence of chemical crosslinking and heat treatments on the swelling degree, resistance to compaction, mechanical strength, and morphology of porous PVA membranes was extensively studied. The crosslinking degree and crystallinity of the membranes, calculated from IR spectra, increased with the treatment time. The porosity, calculated on the basis of swelling experiments, showed a decreasing trend for heat‐treated membranes but remained almost at a constant value for crosslinked membranes. Such a change was further proved with scanning electron microscopy pictures. The behavior was explained by the rearrangement of PVA chains during the heat‐treatment process, which led to morphological changes in the membranes. The mechanical properties of the porous membranes in dry and wet states were measured, and a great difference was observed between crosslinked and heat‐treated membranes in the dry and wet states. The crosslinked membranes showed good mechanical properties in the dry state but became fragile in the wet state. On the contrary, the heat‐treated membranes were more flexible in the wet state than in the dry state. This change was explained by the turnaround of inner stress in the systems during the swelling process. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Development of high‐absorbent light‐weight sanitary napkin
Authors: Das A. , Kothari V. K. , Makhija S. , Avyaya K.
Published: October 2007

This article presents a method of preparing the absorbent core for an ultrathin sanitary napkin using super absorbent fiber (SAF) and viscose fiber blends with varying SAF percentages and mass per unit area (g/m2). The SAF/viscose blended carded webs were sandwiched between two layers of nonwoven fabric to integrate and encapsulate it. The prepared napkin samples showed significantly better rates of absorption for saline solution even though the glass tube wicking (gravimetric) test gave only comparable results. The saturation absorption of the core also follows a definite trend, dependent on two variables, i.e., mass per unit area (g/m2) of the core web and proportion of SAF in the core web. Based on the results, the absorption of the core has been optimized and equations have been developed for prediction of the absorption of the core from mass per unit area and the proportion of SAF in the core web. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Preparation of isotacticity‐rich poly(tert‐butyl vinyl ether) by the cationic polymerization of tert‐butyl vinyl ether with dimethyl[rac‐ethylenebis(indenyl)]zirconium and tri(pentafluorophenyl)borane
Authors: Kwon Oh Wook , Noh Seok Kyun , Lyoo Won Seok
Published: October 2007

tert‐Butyl vinyl ether (tBVE) was polymerized with the catalyst dimethyl[rac‐ethylenebis(indenyl)] zirconium (ansa‐zirconocene) with tri(pentafluorophenyl) borane [B(C6F5)3] as a cocatalyst. The effects of various polymerization conditions, such as the polymerization time, type of polymerization solvent, polymerization temperature, and catalyst concentration, on the conversion of tBVE into poly(tBVE), its molecular weight and molecular weight distribution, and its stereoregularity were investigated. The maximum conversion of tBVE into poly(tBVE) was over 90% at a polymerization temperature of −30°C with an ansa‐zirconocene and B(C6F5)3 concentration of 3.0 × 10−7 mol/mol of tBVE, respectively. The number‐average molecular weights of poly(tBVE) ranged from approximately 14,000 to 20,000, with a lower polydispersity index (weight‐average molecular weight/number‐average molecular weight) ranging from 1.48 to 1.77, at all polymerization temperatures. The number‐average molecular weight of poly(tBVE) increased with decreases in the polymerization temperature and catalyst concentration. The mm triad sequence fraction of poly(tBVE) polymerized with ansa‐zirconocene/B(C6F5)3 at −30°C was much higher than that of poly(tBVE) polymerized with the B(C6F5)3 catalyst at −30°C, and this indicated that the ansa‐zirconocene/B(C6F5)3 catalyst system affected the isospecific polymerization of tBVE. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Influence of amino group pKa on the properties of stimuli‐responsive piperazine‐based polymers and hydrogels
Authors: Roshan Deen G. , Gan L. H.
Published: October 2007

Linear homopolymers of N‐acryloyl‐N′‐alkyl piperazine (N′‐alkyl: methyl, ethyl, or propyl) and their corresponding crosslinked hydrogels were prepared. The polymers showed good responses to changes in the pH of the medium due to the presence of tertiary amine functions that could be protonated at a low pH. The nature of the N′‐alkyl group attached to the piperazine amino nitrogen greatly affected the pKa of the amino group. This in turn influenced the solution behavior of the polymers and was studied with light scattering, potentiometry, and viscosity measurements. The basicity of the polymers increased with an increase in the chain length of the N′‐alkyl substituent. The intrinsic viscosity of the polymers in a good polar organic solvent such as dimethylformamide decreased slightly with increasing temperature because of decreased thermodynamic affinity (interaction) at high temperatures. The viscosity behavior of the polymers in sodium chloride solutions was similar to that of classical polyelectrolytes. The swelling property of the hydrogels was studied with water sorption measurements, and the swelling was by anomalous (non‐Fickian) transport. The diffusion coefficient of the gels in solutions of pH 2.6 increased with increasing N′‐alkyl chain length, whereas at neutral pH, the effect was reversed. This behavior was attributed to the increase in both the basicity and hydrophobicity of the gels with an increase in the chain length of the N′‐alkyl groups. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Styrene‐assisted grafting of maleic anhydride onto polypropylene by reactive processing
Authors: Bettini S. H. P. , Ruvolo Filho A. C.
Published: October 2007

The grafting of maleic anhydride (MA) onto polypropylene (PP) was performed in the presence of the electron‐donating monomer styrene (ST) according to a central composite experimental design, in which the initial MA and ST concentrations were varied. The grafting of MA onto PP in the absence of ST was also performed. All reactions were carried out in the molten state in a Haake rheometer. The amount of reacted MA and the extent of degradation in PP were determined by means of Fourier transform infrared spectroscopy and melt flow index (MFI) measurements, respectively. The results showed that the presence of ST in the reactive processing caused a reduction in MFI and an increase in the level of reacted MA when the initial MA concentration equaled the initial ST concentration. An increase in the initial MA concentration presented distinct behavior that depended on the ST content. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Yttria–polystyrene–polypropylene composite for fine dyeable fibers
Authors: Yu Chengbing , Jiang Chong , Chen Yanmo
Published: October 2007

Fine polypropylene fiber has many excellent properties, but it is difficult to dye because of the absence of dye sites in the molecular chain and high crystallinity. Fine polypropylene/hybrid polystyrene (yttria) fiber melt‐spun from blends of polypropylene and a small amount of nanohybrid polystyrene with modified yttria incorporated was prepared to improve the dyeing properties. The dyeability, orientation, degree of crystallinity, phase morphology, and mechanical properties of pure polypropylene and the blend fibers were investigated. It was found that the crystallinity and morphology of these phases in the blend systems were different. With the existence of nanohybrid polystyrene, the fine modified polypropylene filaments had practical mechanical properties, the amorphous region of the polypropylene/hybrid polystyrene (yttria) fiber increased, and the modified polypropylene fiber dyed easily and had good fastness to soaping because of the complexation of the disperse dye and yttrium in the blend system. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Integrated Micro Flow Synthesis Based on Sequential Br–Li Exchange Reactions of p‐, m‐, and o‐Dibromobenzenes
Authors: Nagaki Aiichiro , Tomida Yutaka , Usutani Hirotsugu , Kim Heejin , Takabayashi Naofumi , Nokami Toshiki , Okamoto Hideho , Yoshida Jun‐ichi
Published: October 2007

A micro flow system consisting of micromixers and microtube reactors provides an effective method for the introduction of two electrophiles onto p‐, m‐, and o‐dibromobenzenes. The Br–Li exchange reaction of p‐dibromobenzene with nBuLi can be conducted by using the micro flow system at 20 °C, although much lower temperatures (<−48 °C) are needed for a batch reaction. The resulting p‐bromophenyllithium was allowed to react with an electrophile in the micro flow system at 20 °C. The p‐substituted bromobenzene thus obtained was subjected to a second Br–Li exchange reaction followed by reaction with a second electrophile at 20 °C in one flow. A similar transformation can be carried out with m‐dibromobenzene by using the micro flow system. However, the Br–Li exchange reaction of o‐dibromobenzene followed by reaction with an electrophile should be conducted at −78 °C to avoid benzyne formation. The second Br–Li exchange reaction followed by reaction with an electrophile can be carried out at 0 °C. By using the present method, a variety of p‐, m‐, and o‐disubstituted benzenes were synthesized in one flow at much higher temperatures than are required for conventional batch reactions.
Why circumcision is a biomedical imperative for the 21stcentury
Authors: Morris Brian J.
Published: October 2007

Circumcision of males represents a surgical “vaccine“ against a wide variety of infections, adverse medical conditions and potentially fatal diseases over their lifetime, and also protects their sexual partners. In experienced hands, this common, inexpensive procedure is very safe, can be pain‐free and can be performed at any age. The benefits vastly outweigh risks. The enormous public health benefits include protection from urinary tract infections, sexually transmitted HIV, HPV, syphilis and chancroid, penile and prostate cancer, phimosis, thrush, and inflammatory dermatoses. In women circumcision of the male partner provides substantial protection from cervical cancer and chlamydia. Circumcision has socio‐sexual benefits and reduces sexual problems with age. It has no adverse effect on penile sensitivity, function, or sensation during sexual arousal. Most women prefer the circumcised penis for appearance, hygiene and sex. Given the convincing epidemiological evidence and biological support, routine circumcision should be highly recommended by all health professionals. BioEssays 29:1147–1158, 2007. © 2007 Wiley Periodicals, Inc.
Playing only one instrument may be not enough: Limitations and future of the antiangiogenic treatment of cancer
Authors: Quesada Ana R. , Medina Miguel Ángel , Alba Emilio
Published: October 2007

Angiogenesis plays an essential role in tumor growth, invasion and metastasis. After initial pessimism about the usefulness of the antiangiogenic therapeutic approach for cancer, interest has increased in the development of antiangiogenic compounds after the first clinical approval of an antiangiogenic therapy. The anti‐vascular endothelial growth factor (VEGF) antibody bevacizumab has recently been approved for use in combination with chemotherapy for the treatment of metastatic colorectal and non‐small cell lung cancer patients. However, no survival benefit has been demonstrated in anti‐VEGF monotherapy trials, probably due to the high complexity of tumor angiogenesis regulation. Experimental and clinical data, including the approval of the multitargeted drugs sunitinib and sorafenib, indicate that exciting results, including tumor regression, can be expected from the combined targeting of different pathways in the tumor angiogenesis scenario. Several obstacles, including the high cost of new molecular targeted drugs make this therapeutic approach difficult. BioEssays 29:1159–1168, 2007. © 2007 Wiley Periodicals, Inc.
Bioelectricity and epimorphic regeneration
Authors: Stewart Scott , Rojas‐Muñoz Agustin , Belmonte Juan Carlos Izpisúa
Published: October 2007

All cells have electric potentials across their membranes, but is there really compelling evidence to think that such potentials are used as instructional cues in developmental biology? Numerous reports indicate that, in fact, steady, weak bioelectric fields are observed throughout biology and function during diverse biological processes, including development. Bioelectric fields, generated upon amputation, are also likely to play a key role during vertebrate regeneration by providing the instructive cues needed to direct migrating cells to form a wound epithelium, a structure unique to regenerating animals. However, mechanistic insight is still sorely lacking in the field. What are the genes required for bioelectric‐dependent cell migration during regeneration? The power of genetics combined with the use of zebrafish offers the best opportunity for unbiased identification of the molecular players in bioelectricity. BioEssays 29:1133–1137, 2007. © 2007 Wiley Periodicals, Inc.
Control of male germ‐cell development in flowering plants
Authors: Singh Mohan B. , Bhalla Prem L.
Published: October 2007

Plant reproduction is vital for species survival, and is also central to the production of food for human consumption. Seeds result from the successful fertilization of male and female gametes, but our understanding of the development, differentiation of gamete lineages and fertilization processes in higher plants is limited. Germ cells in animals diverge from somatic cells early in embryo development, whereas plants have distinct vegetative and reproductive phases in which gametes are formed from somatic cells after the plant has made the transition to flowering and the formation of the reproductive organs. Recently, novel insights into the molecular mechanisms underlying male germ‐line initiation and male gamete development in plants have been obtained. Transcriptional repression of male germ‐line genes in non‐male germ‐line cells have been identified as a key mechanism for spatial and temporal control of male germ‐line development. This review focuses on molecular events controlling male germ‐line development especially, on the nature and regulation of gene expression programs operating in male gametes of flowering plants. BioEssays 29:1124–1132, 2007. © 2007 Wiley Periodicals, Inc.
A biological cosmos of parallel universes: Does protein structural plasticity facilitate evolution?
Authors: Meier Sebastian , Özbek Suat
Published: October 2007

While Darwin pictured organismal evolution as “descent with modification” more than 150 years ago, a detailed reconstruction of the basic evolutionary transitions at the molecular level is only emerging now. In particular, the evolution of today's protein structures and their concurrent functions has remained largely mysterious, as the destruction of these structures by mutation seems far easier than their construction. While the accumulation of genomic and structural data has indicated that proteins are related via common ancestors, naturally occurring protein structures are often considered to be evolutionarily robust, thus leaving open the question of how protein structures can be remodelled while selective pressure forces them to function. New information on the proteome, however, increasingly explains the nature of local and global conformational diversity in protein evolution, which allows the acquisition of novel functions via molecular transition forms containing ancestral and novel structures in dynamic equilibrium. Such structural plasticity may permit the evolution of new protein folds and help account for both the origins of new biological functions and the nature of molecular defects. BioEssays 29:1095–1104, 2007. © 2007 Wiley Periodicals, Inc.
The long and the short of RNA maps
Authors: Ponjavic Jasmina , Ponting Chris P.
Published: October 2007

The landscapes of mammalian genomes are characterized by complex patterns of intersecting and overlapping sense and antisense transcription, giving rise to large numbers of coding and non‐protein‐coding RNAs (ncRNAs). A recent report by Kapranov and colleagues1 describes three potentially novel classes of RNAs located at the very edges of protein‐coding genes. The presence of RNAs from one of these classes appears to be correlated with the expression levels of their associated genes. These results suggest that a proportion of these RNAs might have roles in the cis‐regulation of neighbouring protein‐coding genes' expression. BioEssays 29:1077–1080, 2007. © 2007 Wiley Periodicals, Inc.
Strength in numbers: High phenotypic variance in early Cambrian trilobites and its evolutionary implications
Authors: Hughes Nigel C.
Published: October 2007

Analysis of the degree of intraspecific morphological polymorphism during the evolutionary history of trilobites using an informatic approach1 provides striking evidence of a long‐suspected but previously unsubstantiated pattern: degrees of polymorphism are markedly higher in phylogenetically basal, stratigraphically early species. This unequivocal pattern prompts further exploration of the relationship between microevolutionary variance and macroevolutionary history. It demonstrates that the ‘traditional’ fossil record of skeletonized organisms can provide unique insight into questions of major evolutionary interest. BioEssays 29:1081–1084, 2007. © 2007 Wiley Periodicals, Inc.
Biotechnology of flavonoids and other phenylpropanoid‐derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes
Authors: Ververidis Filippos , Trantas Emmanouil , Douglas Carl , Vollmer Guenter , Kretzschmar Georg , Panopoulos Nickolas
Published: October 2007

Plant natural products derived from phenylalanine and the phenylpropanoid pathways are impressive in their chemical diversity and are the result of plant evolution, which has selected for the acquisition of large repertoires of pigments, structural and defensive compounds, all derived from a phenylpropanoid backboneviathe plant‐specific phenylpropanoid pathway. These compounds are important in plant growth, development and responses to environmental stresses and thus can have large impacts on agricultural productivity. While plant‐based medicines containing phenylpropanoid‐derived active components have long been used by humans, the benefits of specific flavonoids and other phenylpropanoid‐derived compounds to human health and their potential for long‐term health benefits have only been recognized more recently. In this part of the review, we discuss in detail the recent strategies and achievements used in the reconstruction of multienzyme pathways in plants and microbes in an effort to be able to attain higher amounts of the desired flavonoids and stilbenoids exploiting their beneficial properties as analyzed extensively in Part I of this review.
4‐Chloroprolines: Synthesis, conformational analysis, and effect on the collagen triple helix
Authors: Shoulders Matthew D. , Guzei Ilia A. , Raines Ronald T.
Published: October 2007

Collagen is an abundant, triple‐helical protein comprising three strands of the repeating sequence: Xaa–Yaa–Gly. (2S)‐Proline and (2S,4R)‐4‐hydroxyproline (Hyp) are common in the primary structure of collagen. Here, we use nonnatural proline derivatives to reveal determinants of collagen stability. Specifically, we report high‐yielding syntheses of (2S,4S)‐4‐chloroproline (clp) and (2S,4R)‐4‐chloroproline (Clp). We find that the molecular structure of Ac‐Clp‐OMe in the solid state is virtually identical to that of Ac‐Hyp‐OMe. In contrast, the conformational properties of Ac‐clp‐OMe are similar to those of Ac‐Pro‐OMe. Ac‐Clp‐OMe has a stronger preference for a trans amide bond than does Ac‐Pro‐OMe, whereas Ac‐clp‐OMe has a weaker preference. (Pro–Clp–Gly)10 forms triple helices that are significantly more stable than those of (Pro–Pro–Gly)10. Triple helices of (clp–Pro–Gly)10 have stability similar to those of (Pro–Pro–Gly)10. Unlike (Pro–Clp–Gly)10 and (clp–Pro–Gly)10, (clp–Clp–Gly)10 does not form a stable triple helix, presumably due to a deleterious steric interaction between proximal chlorines on different strands. These data, which are consistent with previous work on 4‐fluoroprolines and 4‐methylprolines, support the importance of stereoelectronic and steric effects in the stability of the collagen triple helix and provide another means to modulate that stability. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 443–454, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Biomembranen – Wächter des zellulären Grenzverkehrs. Von Pumpen, Carriern und Kanälen
Authors: Bernhardt Ingolf
Published: October 2007

Für das Verständnis der Funktion einer biologischen Membran ist die Kenntnis der Struktur sowie der Dynamik der Membranbestandteile (Lipide, Proteine) eine essenzielle Voraussetzung. Der Transport von biologisch relevanten Substanzen und Ionen über die Barriere einer biologischen Membran erfolgt durch spezifische Transportmechanismen, die man in verschiedene Kategorien einteilen kann (Pumpen, Carrier, Kanäle). Werden alle spezifischen Transporter blockiert oder gehemmt, kann man einen Rest‐(“Leak”)‐Transport messen, für den es verschiedene Gründe gibt.
Kalt, kälter, am kältesten
Authors: Hille‐Rehfeld Annette
Published: October 2007

Um schädlichen Umwelteinflüssen zu entgehen, enthält unsere Haut eine Vielfalt von Schmerzsinneszellen, deren Erregung unter anderem motorische Funktionen steuert und so Ausweichreaktionen auslöst. Dazu gehören thermosensitive Zellen, durch die wir beispielsweise unangenehm kühle Temperaturen von schädlicher Kälte unterscheiden können. Dass einige Thermosensoren gleichzeitig auch Chemosensoren darstellen, ist die Grundlage für bekannte Sinnestäuschungen.
Assoziation zwischen Herzerkrankungen und Depressionen
Authors: Baghai Thomas C. , Binder Elisabeth , Schüle Cornelius , Lucae Susanne , Eser Daniela , Müller‐Myhsok Bertram , Möller Hans‐Jürgen , Holsboer Florian , Rupprecht Rainer , Bondy Brigitta
Published: October 2007

Veränderungen im ACE‐Gen erhöhen möglicherweise das Risiko für Depressionen und kardiovaskuläre Erkrankungen. Forschungen der vergangenen Jahre zeigten bereits, dass zwischen diesen Krankheiten eine unheilvolle Allianz besteht: Koronare Herzerkrankungen steigern das Risiko für Depressionen, diese wiederum verschlechtern die Prognose bei koronaren Herzerkrankungen. Eine Schlüsselrolle spielt dabei offensichtlich das Gen für das Angiotensin‐Converting‐Enzym (ACE‐Gen), das die Entstehung von koronaren Herzerkrankungen beeinflusst.
Die Rolle des fetalen Kälberserums in Zellkulturmedien
Authors: Schrödel Andrea
Published: October 2007

Zellkulturexperimente können die Anzahl von Tierversuchen in der Grundlagenforschung drastisch reduzieren und finden daher eine breite Anwendung. Um Zellen in Kultur zu halten, muss eine Umgebung geschaffen werden, die das Wachstum und die Teilung der Zellen erlaubt. Hierzu sind seit Beginn des 20. Jahrhunderts diverse Medien entwickelt worden. Üblicherweise wird auch heute noch ein gewisser Anteil an Fetalem Kälberserum dem Kulturmedium zugemengt.
Nonlinear calibrations on the assay of dilitiazem and two of its metabolites from plasma samples by means of liquid chromatography and ESI/MS2 detection: application to a bioequivalence study
Authors: Georgita Cristina , Albu Florin , David Victor , Medvedovici Andrei
Published: October 2007

The assay of diltiazem (DLTZ) and its active metabolites desacetyldiltiazem (DAcD) and desmethyldiltiazem (DMeD) in plasma samples was achieved by means of an HPLC/(ESI)MS2 method. The diastereoisomer of diltiazem, namely {(2R,3S)‐5‐[2‐(dimethylamino)ethyl]‐2‐(4‐methoxyphenyl)‐4‐oxo‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepin‐3‐yl acetate} was used as internal standard (IS). Sample preparation was based on protein precipitation by means of organic solvent addition (acetonitrile). The isocratic elution based on a reversed‐phase mechanism allows good separation of the analytes within 15 min. Atmospheric pressure electrospray ionization was used. All analytes were monitored in the MS2‐MRM mode. A fragmentation schema is proposed for the target compounds. As the method was designed for bioequivalence purposes, a full validation procedure was considered. On validation, nonlinear calibrations were observed. Consequently, concentration intervals requiring nonlinear calibrations are discussed. Low limits of quantification in the 0.6–1 ng/mL concentration range were obtained. The analytical method was successfully applied to a single dose (120 mg), open‐label, randomized, two‐period, two‐sequence, crossover bioequivalence study of two commercially available solid oral dosage pharmaceutical formulations (tablets). Copyright © 2007 John Wiley & Sons, Ltd.
Clenbuterol marketed as dietary supplement
Authors: Parr Maria K. , Koehler Karsten , Geyer Hans , Guddat Sven , Schänzer Wilhelm
Published: October 2007

In several studies it has been demonstrated that products containing pharmaceutically active ingredients are marketed as dietary supplements. Most of these products contain anabolic steroids. Recently products for weight loss containing active drugs have also appeared on the market. In the present case a healthy male ordered the product ‘Anabolic burner’ via the Internet. The product was received from a German dispatcher and paid by bank transfer to a German bank account. After ingesting one tablet he reported tremor and delivered a urine sample. This urine was found to contain 2 ng/mL of clenbuterol utilizing LC‐MS/MS analysis. Additionally the product itself was analyzed with GC‐MS for clenbuterol, yielding a content of about 30 µg per tablet. The beta‐2 agonist clenbuterol is only legally available on prescription and is classified as prohibited doping substance in sports. The present case for the first time confirms the presence of clenbuterol in a dietary supplement. It again demonstrates the common problem with products on the supplement market, where non‐licensed pharmaceuticals and doping substances are easily available. The ingestion of these products containing additions of therapeutic drugs can lead to side effects and/or interactions with conventional medicines. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of huperzine A in human plasma by liquid chromatography–electrospray tandem mass spectrometry: application to a bioequivalence study on Chinese volunteers
Authors: Li Wei , Li Jianhua , Hu Qin
Published: October 2007

A simple, sensitive and selective LC‐MS‐MS method has been developed for the quantification of huperzine A in human plasma. Huperzine A and pseudoephedrine hydrochloride (internal standard) were isolated from human plasma by extraction with ethyl acetate, chromatographed on a C18 column with a mobile phase consisting of 0.2% formic acid–methanol (15:85, v/v) and detected using a tandem mass spectrometer with an electrospray ionization interface. The lower limit of quantification was 0.0508 ng/mL, and the assay exhibited a linear range of 0.0508–5.08 ng/mL (r = 0.9998). The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test vs reference product) in 18 healthy male Chinese volunteers. After a single 0.2 mg dose for the test and reference product, the resulting means of major pharmacokinetic parameters such as AUC0−24, AUC0−∞, Cmax, Tmax and t1/2 of huperzine A were 16.35 ± 3.42 vs 16.38 ± 3.61 ng h/mL, 17.53 ± 3.80 vs 17.70 ± 3.97 ng h/mL, 2.47 ± 0.49 vs 2.51 ± 0.51 ng/mL, 1.3 ± 0.4 vs 1.2 ± 0.3 h and 5.92 ± 0.75 vs 6.18 ± 0.66 h, respectively, indicating that these two kinds of tablets were bioequivalent. Copyright © 2007 John Wiley & Sons, Ltd.
Insight Into the Kinetic of Amyloid β (1–42) Peptide Self‐Aggregation: Elucidation of Inhibitors’ Mechanism of Action
Authors: Bartolini Manuela , Bertucci Carlo , Bolognesi Maria Laura , Cavalli Andrea , Melchiorre Carlo , Andrisano Vincenza
Published: October 2007

The initial transition of amyloid β (1–42) (Aβ42) soluble monomers/small oligomers from unordered/α‐helix to a β‐sheet‐rich conformation represents a suitable target to design new potent inhibitors and to obtain effective therapeutics for Alzheimer's disease. Under optimized conditions, this reliable and reproducible CD kinetic study showed a three‐step sigmoid profile that was characterized by a lag phase (prevailing unordered/α‐helix conformation), an exponential growth phase (increasing β‐sheet secondary structure) and a plateau phase (prevailing β‐sheet secondary structure). This kinetic analysis brought insight into the inhibitors' mechanism of action. In fact, an increase in the duration of the lag phase can be related to the formation of an inhibitor–Aβ complex, in which the non‐amyloidogenic conformation is stabilized. When the exponential rate is affected exclusively, such as in the case of Congo red and tetracycline, then the inhibitor affinity might be higher for the pleated β‐sheet structure. Finally, by adding the inhibitor at the end of the exponential phase, the soluble protofibrils can be disrupted and the Aβ amyloidogenic structure can revert into monomers/small oligomers. Congo red and tetracycline preferentially bind to amyloid in the β‐sheet conformation because both decreased the slope of the exponential growth, even if to a different extent, whereas no effect was observed for tacrine and galantamine. Some very preliminary indications can be derived about the structural requirements for binding to nonamyloidogenic or β‐sheet amyloid secondary structure for the development of potent antiaggregating agents. On these premises, memoquin, a multifunctional molecule that was designed to become a drug candidate for the treatment of Alzheimer's disease, was investigated under the reported circular dichroism assay and its anti‐amyloidogenic mechanism of action was elucidated.
Integrated, Electrically Contacted NAD(P)+‐Dependent Enzyme–Carbon Nanotube Electrodes for Biosensors and Biofuel Cell Applications
Authors: Yan Yi‐Ming , Yehezkeli Omer , Willner Itamar
Published: October 2007

Integrated, electrically contacted β‐nicotinamide adenine dinucleotide‐ (NAD+) or β‐nicotinamide adenine dinucleotide phosphate‐ (NADP+) dependent enzyme electrodes were prepared on single‐walled carbon nanotube (SWCNT) supports. The SWCNTs were functionalized with Nile Blue (1), and the cofactors NADP+ and NAD+ were linked to 1 through a phenyl boronic acid ligand. The affinity complexes of glucose dehydrogenase (GDH) with the NADP+ cofactor or alcohol dehydrogenase (AlcDH) with the NAD+ cofactor were crosslinked with glutaric dialdehyde and the biomolecule‐functionalized SWCNT materials were deposited on glassy carbon electrodes. The integrated enzyme electrodes revealed bioelectrocatalytic activities, and they acted as amperometric electrodes for the analysis of glucose or ethanol. The bioelectrocatalytic response of the systems originated from the biocatalyzed oxidation of the respective substrates by the enzyme with the concomitant generation of NAD(P)H cofactors. The electrocatalytically mediated oxidation of NAD(P)H by 1 led to amperometric responses in the system. Similarly, an electrically contacted bilirubin oxidase (BOD)–SWCNT electrode was prepared by the deposition of BOD onto the SWCNTs and the subsequent crosslinking of the BOD units using glutaric dialdehyde. The BOD–SWCNT electrode revealed bioelectrocatalytic functions for the reduction of O2 to H2O. The different electrically contacted SWCNT‐based enzyme electrodes were used to construct biofuel cell elements. The electrically contacted GDH–SWCNT electrode was used as the anode for the oxidation of the glucose fuel in conjunction with the BOD–SWCNT electrode in the presence of O2, which acted as an oxidizer in the system. The power output of the cell was 23 μW cm−2. Similarly, the AlcDH–SWCNT electrode was used as the anode for the oxidation of ethanol, which was acting as the fuel, with the BOD–SWCNT electrode as the cathode for the reduction of O2. The power output of the system was 48 μW cm−2.
Water‐Soluble, Electroactive, and Photoluminescent Quaterthiophene–Dinucleotide Conjugates
Authors: Alesi Silvia , Brancolini Giorgia , Melucci Manuela , Capobianco Massimo Luigi , Venturini Alessandro , Camaioni Nadia , Barbarella Giovanna
Published: October 2007

Quaterthiophene–dinucleotide conjugates 5′TA3′‐t4‐3′AT5′, 5′AA3′‐t4‐3′AA5′, and 5′TT3′‐t4‐3′TT5′ (TA: thymidine–adenosine, AA: adenosine–adenosine, TT: thymidine–thymidine) were synthesized and analyzed by a combination of spectroscopy and microscopy, electrical characterization, and theoretical calculations. Circular dichroism (CD) experiments demonstrated a transfer of chirality from the dinucleotides to quaterthiophene at high ionic strength and in cast films. The films were photoluminescent and electroactive. CD and photoluminescence spectra and current density/voltage plots (measured under dynamic vacuum) displayed significant variation on changing the dinucleotide scaffold. Molecular mechanics and molecular dynamics calculations indicated that the conformation and packing modes of the conjugates are the result of a balance between intra‐ and intermolecular nucleobase–thiophene stacking interactions and intramolecular hydrogen bonding between the nucleobases.