bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular analysis of Fanconi anaemia
Authors: Digweed Martin , Sperling Karl
Published: February 2005

The autosomal recessive genetic disease, Fanconi anaemia, is perceived as another manifestation of defective cellular DNA repair, just as in the autosomal recessive disease Xeroderma pigmentosum. The biochemistry and cellular biology of Xeroderma pigmentosum have been convincingly elucidated, but the same has not been true for Fanconi anaemia. In this review we consider the pleiotropic nature of Fanconi anaemia, its clinical and cellular variability and its genetic heterogeneity. We take into account the wealth of experimental findings available and offer a novel hypothesis involving feedback control of DNA replication during S phase of the cell cycle to explain the basic defect in the disease.
Retinoic acid, HOX genes and the anterior‐posterior axis in chordates
Authors: Shimeld Sebastian M.
Published: February 2005

In vertebrate development, the HOX genes act to specify cell identity along much of the anterior‐posterior axis of the embryonic central nervous system. In all vertebrates examined to date, the vitamin A metabolite retinoic acid is implicated in the patterning of the anterior posterior axis and the induction of HOX gene expression. Two recent papers have extended the study of retinoic acid induction of HOX genes to the closest relatives of the vertebrates, amphioxus and tunicates(1,2). In both these species, exogenous retinoic acid is able to induce ectopic expression of HOX 1 genes in the anterior central nervous system. This suggests that retinoic acid control of anterior‐posterior axis formation and HOX induction is not specific to vertebrates. However, in the more distantly related echinoderms and arthropods, retinoic acid does not seem to act in the same way. Thus the role of retinoic acid in anterior‐posterior axis specification may be a chordate innovation, perhaps linked to the evolution of another chordate character, the dorsal neural tube.
Epithelial integrins
Authors: Sheppard Dean
Published: February 2005

The integrin family was originally described as a family of adhesion receptors, utilized by cells for attachment to and migration across components of the extracellular matrix. Epithelial cells in adult tissues are generally stationary cells, but these cells nevertheless express several different integrins. This review will discuss the evidence that integrins on epithelial cells are also likely to function as signaling molecules, allowing these cells to detect attachment or detachment, and changes in the local composition of ligands. Signals initiated by integrins appear to modulate epithelial cell differentiation, proliferation, survival, and gene expression. Because the local concentration of integrin ligands is altered by injury, inflammation, and remodeling, signals initiated through integrins are likely to play important roles in the responses of epithelial cells to each of these processes.
Chromatin architectural proteins and transcription factors: A structural connection
Authors: van Holde Kensal , Zlatanova Jordanka
Published: February 2005

It has long been assumed that the architectural proteins of chromatin (the histones, for example) are unrelated to their functional proteins (transcription factors, polymerases, etc). New studies(1,2)drastically change this perspective. It appears that a portion of the general transcription initiation complex TFIID is made up of proteins that not only carry marked sequence and structural resemblances to the core histones of the nucleosome, but also form an octameric complex similar to the histone octamer. This can now be seen as part of a general pattern of continuity among structural and functional chromatin proteins.
Two is company: The complex travel arrangements of floral homeotic factors
Authors: Davies Brendan
Published: February 2005

The control of floral organ identity has received much attention since the first homeotic genes were isolated five years ago. The homeotic factors may be subject to a bewildering variety of control mechanisms including spatial and temporal transcriptional regulation, autoregulation, mutual protein stabilization, specific heterodimerization, post‐transcriptional modification and interaction with accessory factors. Now another level of complexity has been added by the recent discovery that the ‘B function factors’ depend on each other for nuclear localization(1) and can act non‐cell‐autonomously in a polar fashion(2).
Chloride channels: An emerging molecular picture
Authors: Jentsch Thomas J. , Günther Willy
Published: February 2005

Chloride channels are probably found in every cell, from bacteria to mammals. Their physiological tasks range from cell volume regulation to stabilization of the membrane potential, signal transduction, transepithelial transport and acidification of intracellular organelles. These different functions require the presence of many distinct chloride channels, which are differentially expressed and regulated by various stimuli. These include various intracellular messengers (like calcium and cyclic AMP), pH, extracellular ligands and transmembrane voltage. Three major structural classes of chloride channels are known to date, but there may be others not yet identified. After an overview of the general functions of chloride channels, this review will focus on these cloned chloride channels: the CLC chloride channel family, which includes voltage‐gated chloride channels, and the cystic fibrosis transmembrane regulator (CFTR), which performs other functions in addition to being a chloride channel. Finally, a short section deals with GABA and glycine receptors. Diseases resulting from chloride channel defects will be specially emphasized, together with the somewhat limited information about how these proteins work at the molecular level.
Transcription factors and head formation in vertebrates
Authors: Bally‐Cuif Laure , Boncinelli Edoardo
Published: February 2005

Evidence from Drosophila and also vertebrates predicts that two different sets of instructions may determine the development of the rostral and caudal parts of the body. This implies different cellular and inductive processes during gastrulation, whose genetic requirements remain to be understood. To date, four genes encoding transcription factors expressed in the presumptive vertebrate head during gastrulation have been studied at the functional level: Lim‐1, Otx‐2, HNF‐3β and goosecoid. We discuss here the potential functions of these genes in the formation of rostral head as compared to posterior head and trunk, and in the light of recent fate map and expression analyses in mouse, chick, Xenopus and zebrafish. These data indicate that Lim‐1, Otx‐2 and HNF‐3β may be involved in the same genetic pathway controlling the formation of the prechordal mesendoderm, which is subsequently required for rostral head development. goosecoid may act in a parallel pathway, possibly in conjunction with other, yet unidentified, factors.
The genetics of phototransduction and circadian rhythms in arabidopsis
Authors: Millar Andrew J. , Kay Steve A.
Published: February 2005

A wide range of biological processes, in all eukaryotes and in some prokaryotes, are controlled by rhythms with a period close to 24 hours. The circadian oscillator, which is responsible for generating these rhythms, is controlled by light signals that maintain its synchrony with the environmental day/night cycle. Higher plants exhibit many circadian rhythms, including rhythms in the transcription of specific genes. Molecular tools derived from such clock‐controlled genes have led to the identification of several circadian rhythm mutants in the genetic model, Arabidopsis thaliana. The extensive understanding of photoperception in this species will make it a powerful system with which to investigate the light regulation of circadian rhythms. We compare Arabidopsis rhythms to the results from other systems, and discuss these data with respect to the current phototransduction models.
Butterflies in the spotlight
Authors: Pigliucci Massimo
Published: February 2005

Recent advances in our understanding of developmental phenomena has come from highly interdisciplinary studies where molecular biology, ecology and evolution converge to elucidate fundamental mechanisms, how they change through time, and what function they actually have in the context of the niche of the organism. A recent study on butterfly eyespots(1) pinpoints the surprisingly simple regulatory cascade controlling such an apparently complex phenotype. The implications go beyond the elucidation of a fascinating developmental pathway, into the mechanisms and tempo of speciation and macroevolution.
DNA turnover and mutation in resting cells
Authors: Bridges Bryn A.
Published: February 2005

There is growing evidence that mutations can arise in non‐dividing cells (both bacterial and mammalian) in the absence of chromosomal replication. The processes that are involved are still largely unknown but may include two separate mechanisms. In the first, DNA lesions resulting from the action of endogenous mutagens may give rise to RNA transcripts with miscoded bases. If these confer the ability to initiate DNA replication, the DNA lesions may have an opportunity to miscode during replication and thus could give rise to apparently ‘adaptive’ mutations. A second mechanism is suggested by recent work in starved bacteria, showing that there is much more turnover of chromosomal DNA than has been previously thought. This could permit polymerase errors to lead to mutations in non‐dividing cells. Such cryptic DNA synthesis, which may essentially replace existing DNA rather than duplicating it, could, in principle, act as an additional source of variability on which selection may act, initially in the absence of cell division. In mammals such processes would undoubtedly have implications for germ cell mutagenesis and carcinogenesis.
Schistosomiasis vaccine development — the current picture
Authors: Waine Gary J. , McManus Donald P.
Published: February 2005

Development of a vaccine for schistosomiasis, a parasitic disease currently affecting over 200 million people worldwide, has been targeted as a priority by the World Health Organisation. Research demonstrating the ability of humans to acquire natural immunity to schistosome infection, together with the successful use of attenuated vaccines in animals both under laboratory and field conditions, suggest that development of a human vaccine is feasible. Attenuated vaccines for schistosomiasis are considered neither safe nor practicable for human use, however, and therefore other approaches must be considered. This review examines progress currently being undertaken in a number of different areas towards achieving the goal of a safe and effective human vaccine for schistosomiasis.
Genetic analysis of craniofacial development in the vertebrate embryo
Authors: Schilling Thomas F.
Published: February 2005

Every cartilage and bone in the vertebrate skeleton has a precise shape and position. The head skeleton develops in the embryo from the neural crest, which emigrates from the neural ectoderm and forms the skull and pharyngeal arches. Recent genetic data from mice and zebrafish suggest that cells in the pharyngeal segments are specified by positional information in at least two dimensions, Hox genes along the anterior‐posterior axis and other homeobox genes along the dorsal‐ventral axis within a segment. Many zebrafish and human mutant phenotypes indicate that additional genes are required for the development of groups of adjacent pharyngeal arches and for patterning along the mediolateral axis of the skull. The complementary genetic approaches in humans, mice and fish reveal networks of genes that specify the complex morphology of the head skeleton along a relatively simple set of coordinates.
PDZ Domains: Targeting signalling molecules to sub‐membranous sites
Authors: Ponting Christopher P. , Phillips Christopher , Davies Kay E. , Blake Derek J.
Published: February 2005

PDZ (also called DHR or GLGF) domains are found in diverse membraneassociated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin‐associated proteins, collectively known as syntrophins. Many PDZ domain‐containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C‐terminal polypeptides of a subset of NMDA receptor subunits and/or with Shaker‐type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand‐binding and the structural bases for sequence conservation among diverse PDZ domains.
Ordering microtubules
Authors: Haimo Leah T.
Published: February 2005

How do cells order their cytoplasm? While microtubule organizing centers have long been considered essential to conferring order by virtue of their microtubule nucleating activity, attention has currently refocused on the role that microtubule motors play in organizing microtubules. An intriguing set of recent findings(1) reveals that cell fragments, lacking microtubule organizing centers, rapidly organize microtubules into a radial array during organelle transport driven by the microtubule motor, cytoplasmic dynein. Further, interaction of radial microtubules with the cell surface centers the array, revealing that centering information resides not with centrosomes but with organized microtubules.
Looking into the sea urchin embryo you can see local cell interactions regulate morphogenesis
Authors: Wilt Fred H.
Published: February 2005

The transparent sea urchin embryo provides a laboratory for study of morphogenesis. The calcareous endoskeleton is formed by a syncytium of mesenchyme cells in the blastocoel. The locations of mesenchyme in the blastocoel, the size of the skeleton, and even the branching pattern of the skeletal rods, are governed by interactions with the blastula wall. Now Guss and Ettensohn(1) show that the rate of deposition of CaCO3 in the skeleton is locally controlled in the mesenchymal syncytium, as is the pattern of expression of three genes involved in skeleton formation. They propose that short range signals emanating from the blastula wall regulate many aspects of the biomineralization process.
Molecular aspects of the epithelial phenotype
Authors: Davies Jamie A. , Garrod David R.
Published: February 2005

Epithelia can be defined morphologically as tissues that line surfaces, and ultrastructurally with reference to their cells' apico‐basal polarity and possession of specific cell‐cell junctions. Defining the epithelial phenotype at a molecular level is more problematic ‐ while it is easy to name proteins (e.g. keratins) expressed by a “typical” epithelium, no known molecules are expressed by every epithelium but by no other tissues. Cells can differentiate to and from the epithelial state as part of normal development, as a response to disease or when manipulated in culture. Many factors (matrix components, adhesion molecules, growth factors, transcription factors) have been identified that can trigger these transitions of phenotype in specific cases, but to date no general master regulators of the epithelial state have been found. The epithelial state may therefore be controlled by multiple regulatory genes so that there is no single molecule responsible for all of the diverse types of epithelium that exist in higher animals.
Duchenne muscular dystrophy and the neuromuscular junction: The utrophin link
Authors: Gramolini Anthony O. , Jasmin Bernard J.
Published: February 2005

Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic ‘knockout’ experiments(1,2), a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology(3). In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the neuromuscular synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse‐specific expression to the utrophin gene(4,5). Identification of the events culminating in the transaction of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy for DMD.
Transmission of mitochondrial DNA ‐ playing favorites?
Authors: Boore Jeffrey L.
Published: February 2005

Mitochondria are essential subcellular organelles containing an extranuclear genome (mtDNA). Mutations in mtDNA have recently been identified as causing a variety of human hereditary diseases. In most of these cases, the tissues of the affected individual contain a mixture of mutant and normal mtDNA, with this ratio determining the severity of symptoms. Stochastic factors alone have generally been believed to determine this ratio. Jenuth et al.(1), however, examining mice that contain a mixture of mtDNA types, show evidence of strong selective forces at work in favoring one mtDNA variant over another in some tissues.
The molecular genetics of male infertility
Authors: Elliott David J. , Cooke Howard J.
Published: February 2005

Spermatogenesis is an elaborate process involving both cell division and differentiation, and cell‐cell interactions. Defects in any of these processes can result in infertility, and in some cases these can be genetic in cause. Mapping experiments have defined at least three regions of the human Y chromosome that are required for normal spermatogenesis. Two of these contain the genes encoding the RNA binding proteins RBM and DAZ, suggesting that the control of RNA metabolism is likely to be an important control point for human spermatogenesis. A similar analysis in mice has shown that at least two regions of the mouse Y chromosome are essential for spermatogenesis. Both genetic and reverse genetic approaches have been used to identify mouse autosomal genes required for spermatogenesis. These studies have shown that genes in a number of different pathways are essential for normal spermatogenesis, and also provide putative models of human infertility.
The chromosomal signal for sex determination in Caenorhabditis elegans
Authors: Meneely Philip M.
Published: February 2005

In Caenorhabditis elegans, sex is determined by the number of X chromosomes which, in turn, determines the expression of the X‐linked gene xol‐1. Recent work(1) has shown that xol‐1 expression is controlled by least two distinct regulatory mechanisms, one transcriptional and another post‐transcriptional. The transcriptional regulator is a repressor acting in XX embryos; although the specific gene has not been identified, the chromosome region has been defined. A previously defined regulator of xol‐1, known as fox‐1, maps to a different region of the X chromosome and works post‐transcriptionally, consistent with the identification of the fox‐1 gene product as a putative RNA binding protein(2).
Root development: Signaling down and around
Authors: Wysocka‐Diller Joanna W. , Benfey Philip N.
Published: February 2005

Because of its elegant simplicity, the Arabidopsis root has become a model for studying plant organogenesis. In this review we focus on recent results indicating the importance of signaling in root development. A role for positional information in root cell specification has been demonstrated by ablation analyses. Through mutational analysis, genes have been identified that play a role in radial pattern formation. The embryonic phenotypes of these mutants raised the possibility that division patterns in post‐embryonic roots are dependent on signaling that originates during embryonic development. Analysis of expression of the SCARECROW gene indicates that it may play a role in this ‘top‐down’ signaling process. Characterization of root epidermis development has led to the identification of negative regulators of root‐hair formation. These appear to set up a prepattern which is reinforced by signaling by plant hormones.
Budding of enveloped viruses from the plasma membrane
Authors: Cadd Tamarra L. , Skoging Ulrica , Liljeström Peter
Published: February 2005

Many enveloped viruses are released from infected cells by maturing and budding at the plasma membrane. During this process, viral core components are incorporated into membrane vesicles that contain viral transmembrane proteins, termed ‘spike’ proteins. For many years these spike proteins, which are required for infectivity, were believed to be incorporated into virions via a direct interaction between their cytoplasmic domains and viral core components. More recent evidence shows that, while such direct interactions drive budding of alphaviruses, this may not be the case for negative strand RNA viruses and retroviruses. These viruses can bud particles in the absence of spike proteins, using only viral core components to drive the process. In some cases the spike proteins, without the viral core, can be released as virus‐like particles. Optimal budding and release may, therefore, depend on a ‘push‐and‐pull’ concerted action of core and spike, where oligomerization of both components plays a crucial role.
Antimicrobial peptide defense in Drosophila
Authors: Meister Marie , Lemaitre Bruno , Hoffmann Jules A.
Published: February 2005

Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides. These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 μM. Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned. The induction of the gene encoding the antifungal peptide relies on the spätzle/Toll/cactus gene cassette, which is involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine‐induced activation of NF‐ϰB in mammalian cells. An additional pathway, dependent on the as yet unidentified imd (for immune‐deficiency) gene, is required for the full induction of the antibacterial peptide genes. Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively. Recent data on the molecular mechanisms underlying recognition of non‐self are also discussed in this review.
Relationship between hormone receptor status and tumour size, grade and comedo necrosis in ductal carcinoma in situ
Authors: Barnes N L P , Boland G P , Davenport A , Knox W F , Bundred N J
Published: February 2005

Background

Results of the National Surgical Adjuvant Breast Project B-24 trial indicate that adjuvant tamoxifen therapy is of benefit only in oestrogen receptor (ER)- positive ductal carcinoma in situ (DCIS). In the UK, ER status is not routinely determined in DCIS. The aim of this study was to assess the ER status in women with DCIS to determine whether any clinicopathological factors could predict positivity instead of immunohistochemical assessment.

Methods

The ER and progesterone receptor (PR) status of consecutive women diagnosed with DCIS during 2001 and 2002 was determined by immunohistochemistry.

Results

One hundred and nineteen tumours diagnosed between 2001 and 2002 were analysed; 73·0 per cent were ER positive and 61·1 per cent were PR positive. PR positivity was associated with ER positivity (P < 0·001). Increasing tumour grade correlated with a decrease in ER and PR positivity (both P = 0·002). Comedo necrosis was associated with ER negativity (P = 0·026), PR negativity (P = 0·033) and a lower percentage of ER expression in ER-positive tumours (mean(s.d.) 82(27) versus 93(10) per cent; P = 0·021).

Conclusion

Tumour grade and comedo necrosis were not strong enough predictors to be used as surrogates for immunohistochemical assessment. ER status should be determined before commencing endocrine therapy.
Analysis of antioxidant compounds in sweet orange peel by HPLC–diode array detection–electrospray ionization mass spectrometry
Authors: Anagnostopoulou Maria A. , Kefalas Panagiotis , Kokkalou Eugenios , Assimopoulou Andreana N. , Papageorgiou Vassilios P.
Published: February 2005

HPLC–diode array detection–electrospray ionization mass spectrometry was used to determine qualitatively and quantitatively the ﬂavonoid content of several fractions and residues of extracts of Greek navel sweet orange peel (Citrus sinensis) from the region of southern Greece (Leonidi‐Tripoli). The main groups of ﬂavonoids found according to HPLC retention times, spectral data and literature references were polymethoxylated ﬂavones, C‐glycosylated ﬂavones, O‐glycosylated ﬂavones, O‐glycosylated ﬂavanones, ﬂavonols and phenolic acids and their derivatives. The ethyl acetate fraction which has been shown in previous work to possess the best radical scavenging activity among the others was found to contain C‐glycosylated ﬂavones, polymethoxylated ﬂavones, O‐glycosylated ﬂavones, O‐glycosylated ﬂavanones, two phenolic acid derivatives and two unknown compounds, all in low concentrations. The group of C‐glycosylated ﬂavones was reported for the ﬁrst time in the peel of Navel sweet orange. The C‐glycosylated ﬂavones found according to their spectral characteristics and literature were 6‐C‐β‐glucosyldiosmin, 6,8‐di‐C‐glucopyranosylapigenin, 6,8‐di‐C‐β‐glucosyldiosmin and two unknown. The results suggest that the ethyl acetate fraction of navel Citrus sinensis peel consists of signiﬁcant antioxidant compounds and can be used as a food additive of natural origin or a pharmaceutical supplement using as a source of peel the byproducts of the orange juice industry. Copyright © 2004 John Wiley & Sons, Ltd.
Closure devices and vascular complications among percutaneous coronary intervention patients receiving enoxaparin, glycoprotein IIb/IIIa inhibitors, and clopidogrel
Authors: Exaire J. Emilio , Tcheng James E. , Kereiakes Dean J. , Kleiman Neal S. , Applegate Robert J. , Moliterno David J.
Published: February 2005

The objectives of this study were to explore the rate of vascular complications using closure devices (CDs) vs. manual compression (MC) among percutaneous coronary intervention (PCI) patients receiving enoxaparin, clopidogrel, aspirin, and GP IIb/IIIa inhibitors. The Evaluating Enoxaparin Clotting Times (ELECT) study enrolled patients receiving enoxaparin, clopidogrel, and GP IIb/IIIa inhibitors when necessary. Any approved CD or MC was allowed post‐PCI, and clinical outcome data were prospectively collected. Four hundred forty‐five patients had anti‐Xa levels measured by a core laboratory and by a novel point‐of‐care device that reports ENOX® times. All received enoxaparin, aspirin, and clopidogrel, and 75% received a concomitant GP IIb/IIIa inhibitor. Major and minor bleeding were defined according to TIMI criteria. “Any bleeding” included the occurrence of access site complications including hematoma, significant rebleeding, or bleeding delaying hospital discharge. TIMI major plus minor bleeding occurred in 1.5% of the patients who received CD vs. 1.8% of patients with MC (P = 0.83). Any bleeding occurred in 12.2% of CD vs. 5.7% MC (P = 0.02), and in 9.5% of patients receiving GP IIb/IIIa inhibitor vs. 2.8% (P = 0.01) among those who did not. For patients receiving both a GP IIb/IIIa inhibitor and CD, any bleeding was observed in 13.7% vs. 3.4% (P = 0.006) among patients who received neither. While minor and major TIMI bleeding remained very low in both groups, CD was associated with a twofold increase in risk of any‐bleeding event when compared to MC, especially when using GP IIb/IIIa inhibitors. Catheter Cardiovasc Interv 2005;64:369–372. © 2005 Wiley‐Liss, Inc.
Randomized comparison between Inoue balloon and metallic commissurotome in the treatment of rheumatic mitral stenosis: Immediate results and 6‐month and 3‐year follow‐up
Authors: Guérios Ênio E. , Bueno Ronaldo R.L. , Nercolini Deborah C. , Tarastchuk José C.E. , Andrade Paulo M.P. , Pacheco Álvaro L.A. , Perreto Sônia
Published: February 2005

The metallic commissurotome (MC) technique is a cheaper alternative to the Inoue balloon (IB) technique for percutaneous mitral valvuloplasty (PMV). There are no randomized trials comparing these techniques with longer follow‐up of the patients. The objective of this study was to compare the immediate results and short‐ and medium‐term follow‐up of PMV using either the IB or the MC technique. Fifty patients with rheumatic mitral stenosis were randomly assigned to PMV using the IB (n = 27) or the MC (n = 23) technique. There were no significant differences between the groups regarding baseline clinical, echocardiographic, and hemodynamic data. Clinical and echocardiographic follow‐up were done 6 months and 3 years after the procedure. The success rate was 100% in the IB group and 91.3% in the MC group (P = 0.15); two patients in the latter group developed mitral regurgitation grade 3/4, requiring elective surgery. The mean final mitral valve area was bigger in the MC group (2.17 ± 0.13 vs. 2.00 ± 0.36 cm2; P = 0.04), but after 6‐month and 3‐year follow‐up, this difference was no longer significant (2.06 ± 0.27 vs. 1.98 ± 0.38 cm2, P = 0.22, and 1.86 ± 0.32 vs. 1.87 ± 0.34 cm2, P = 0.89, respectively). This finding suggests valve stretching as an important mechanism of valve dilation with the MC. Three patients in the MC group and two patients in the IB group (P = 0.65) developed mitral valve restenosis; one of them underwent repeat PMV and the other four, all asymptomatic, were clinically followed. PMV performed either with the IB or the MC technique is effective and provides excellent short‐ and medium‐term outcomes regardless of the technique employed. Catheter Cardiovasc Interv 2005;64:301–311. © 2005 Wiley‐Liss, Inc.
Starc II, a multicenter randomized placebo‐controlled double‐blind clinical trial of trapidil for 1‐year clinical events and angiographic restenosis reduction after coronary angioplasty and stenting
Authors: Maresta Aleardo , Balducelli M. , Latini R. , Bernardi G. , Moccetti T. , Sosa C. , Barlera S. , Varani E. , Ribeiro da Silva E.E. , Monici Preti A. , Maggioni A.P.
Published: February 2005

The objective of this study was to investigate the effect of trapidil 200 mg t.i.d. in preventing the occurrence of death, of myocardial infarction and the need for repeat revascularization at 12 months after balloon PTCA with or without stenting. Coronary restenosis after stenting is still a major drawback of percutaneous coronary interventions (PCI) for 30–40% of patients. Trapidil has been shown to prevent restenosis after PTCA. Eligible patients were randomized to placebo or oral trapidil 200 mg t.i.d. at least 48 hr before PCI and continuing 6 months after a successful balloon angioplasty or stent implantation. Aspirin was given to all patients, and ticlopidine 250 mg b.i.d. to those who received a stent for 4 weeks. In a randomized subgroup of 216 patients, quantitative coronary angiography was performed also at 6‐month follow‐up. Out of the 933 patients enrolled, primary endpoint incidence was 20.3% in trapidil and 18.0% in placebo (P = 0.37). When recurrence or deterioration of angina was added to the combined endpoint, incidence was 27.4% in trapidil and 23.0% in placebo (P = 0.12). Restenosis rate in patients with 6‐month angiography was 25.0% in trapidil arm vs. 30.1% in placebo (P = 0.43). Stent restenosis rate was similar in patients randomized to trapidil or placebo (30.2% vs. 23.8%, respectively; P = 0.44), while in patients treated with balloon angioplasty, it was lower in trapidil (17.1%) than in placebo (40.0%; P = 0.03). Oral trapidil 200 mg t.i.d. for 6 months in addition to aspirin did not influence the occurrence of major cardiac events after coronary angioplasty with or without stenting. In a prespecified subgroup of 191 patients treated with balloon angioplasty only, trapidil reduced angiographic restenosis. Catheter Cardiovasc Interv 2005;64:375–382. © 2005 Wiley‐Liss, Inc.
Prediction of Heterofullerene Stabilities: A Combined DFT and Chemometric Study of C56Pt2, C57Pt2and C81Pt2
Authors: Campanera Josep M. , Bo Carles , Balch Alan L. , Ferré Joan , Poblet Josep M.
Published: February 2005

A systematic search of the regioisomers of the heterofullerenes, C57Pt2and C56Pt2, has been carried out by means of density functional calculations to find the most stable structures. Both heterofullerenes incorporate two metal atoms into the fullerene surface. In the case of C57Pt2, one platinum atom substitutes one carbon atom of C60and the other platinum atom replaces a CC bond, whereas in C56Pt2each platinum atom replaces one CC bond. Several geometric factors were studied, three of which have particularly important effects on the relative stabilities of the regioisomers: the PtPt separation, the number of CC bonds remaining after substitution, and the type of CC bond that is substituted. All these factors indicate that the deformation of the carbon framework is a general factor that governs the relative stabilities of the regioisomers. Because a high number of factors affect the stability of the heterofullerenes we also used chemometric techniques in this study. Partial least‐squares (PLS) regression was used to establish the structure–energy relationships of C57Pt2and C56Pt2heterofullerenes. The understanding gained of the factors that affect the relative isomers stabilities has allowed us to predict the stabilities of larger disubstituted carbon cages, for example, C81Pt2heterofullerene.
Structural Analysis of Chiral Complexes of Palladium(0) with 15‐Membered Triolefinic Macrocyclic Ligands
Authors: Pla‐Quintana Anna , Roglans Anna , de Julián‐Ortiz J. Vicente , Moreno‐Mañas Marcial , Parella Teodor , Benet‐Buchholz Jordi , Solans Xavier
Published: February 2005

The complete structural analysis of the palladium complexes of the triolefinic macrocycles (E,E,E)‐1,6,11‐tris(arylsulfonyl)‐1,6,11‐triazacyclopentadeca‐3,8,13‐trienes, which featured from three identical to three different aryl groups, was achieved by performing X‐ray diffraction studies, NMR spectroscopy, and other calculations. The stereochemical complexity is determined by the different isomers formed through complexation of the metal to one or other face of each of the three olefins involved. The palladacyclopropane formulation of the palladium–olefin interaction offers a clear picture of the stereogenicity of the olefin carbon atoms that are complexed to the metal. The energetically favorable isomers were identified in the solid‐state and in solution by performing X‐ray diffraction and NMR spectroscopic analysis, respectively.
An Experimental and Computational Study on the Effect of Al(OiPr)3 on Atom‐Transfer Radical Polymerization and on the Catalyst—Dormant‐Chain Halogen Exchange
Authors: Poli Rinaldo , Stoffelbach François , Maria Sébastien , Mata José
Published: February 2005

Compound Al(OiPr)3 is shown to catalyze the halide‐exchange process leading from [Mo(Cp)Cl2(iPrNCHCHNiPr)] and CH3CH(X)COOEt (X=Br, I) to the mixed‐halide complexes [Mo(Cp)ClX(iPrNCHCHNiPr)]. On the other hand, no significant acceleration is observed for the related exchange between [MoX3(PMe3)3] (X=Cl, I) and PhCH(Br)CH3, by analogy to a previous report dealing with the RuII complex [RuCl2(PPh3)3]. A DFT computation study, carried out on the model complexes [Mo(Cp)Cl2(PH3)2], [MoCl3(PH3)3], and [RuCl2(PH3)3], and on the model initiators CH3CH(Cl)COOCH3, CH3Cl, and CH3Br, reveals that the 16‐electron RuII complex is able to coordinate the organic halide RX in a slightly exothermic process to yield saturated, diamagnetic [RuCl2(PH3)3(RX)] adducts. The 15‐electron [MoCl3(PH3)3] complex is equally capable of forming an adduct, that is, the 17‐electron [MoCl3(PH3)3(CH3Cl)] complex with a spin doublet configuration, although the process is endothermic, because it requires an energetically costly electron‐pairing process. The interaction between the 17‐electron [Mo(Cp)Cl2(PH3)2] complex and CH3Cl, on the other hand, is repulsive and does not lead to a stable 19‐electron adduct. The [RuCl2(PH3)3(CH3X)] system leads to an isomeric complex [RuClX(PH3)3(CH3Cl)] by internal nucleophilic substitution at the carbon atom. The transition state of this process for X=Cl (degenerate exchange) is located at lower energy than the transition state required for halogen‐atom transfer leading to [RuCl3(PH3)3] and the free radical CH3. On the basis of these results, the uncatalyzed halide exchange is interpreted as the result of a competitive SNi process, whose feasibility depends on the electronic configuration of the transition‐metal complex. The catalytic action of Al(OiPr)3 on atom‐transfer radical polymerization (and on halide exchange for the 17‐electron half‐sandwich MoIII complex) results from a more favorable Lewis acid–base interaction with the oxidized metal complex, in which the transferred halogen atom is bound to a more electropositive element. This conclusion derives from DFT studies of the model [Al(OCH3)3]n (n=1,2,3,4) compounds, and on the interaction of Al(OCH3)3 with CH3Cl and with the [Mo(Cp)Cl3(PH3)2] and [RuCl3(PH3)3] complexes.
Axonal development in the cerebral white matter of the human fetus and infant
Authors: Haynes Robin L. , Borenstein Natalia S. , Desilva Tara M. , Folkerth Rebecca D. , Liu Lena G. , Volpe Joseph J. , Kinney Hannah C.
Published: February 2005

After completion of neuronal migration to form the cerebral cortex, axons undergo rapid elongation to their intra‐ and subcortical targets, from midgestation through infancy. We define axonal development in the human parietal white matter in this critical period. Immunocytochemistry and Western blot analysis were performed on 46 normative cases from 20–183 postconceptional (PC) weeks. Anti‐SMI 312, a pan‐marker of neurofilaments, stained axons as early as 23 weeks. Anti‐SMI 32, a marker for nonphosphorylated neurofilament high molecular weight (NFH), primarily stained neuronal cell bodies (cortical, subcortical, and Cajal‐Retzius). Anti‐SMI 31, which stains phosphorylated NFH, was used as a marker of axonal maturity, and showed relatively low levels of staining (approximately one‐fourth of adult levels) from 24–34 PC weeks. GAP‐43, a marker of axonal growth and elongation, showed high levels of expression in the white matter from 21–64 PC weeks and lower, adult‐like levels beyond 17 postnatal months. The onset of myelination, as seen by myelin basic protein expression, was ∼54 weeks, with progression to “adult‐like” staining by 72–92 PC weeks. This study provides major insight into axonal maturation during a critical period of growth, over an age range not previously examined and one coinciding with the peak period of periventricular leukomalacia (PVL), the major disorder underlying cerebral palsy in premature infants. These data suggest that immature axons are susceptible to damage in PVL and that the timing of axonal maturation must be considered toward establishing its pathology relative to the oligodendrocyte/myelin/axonal unit. J. Comp. Neurol. 484:156–167, 2005. © 2005 Wiley‐Liss, Inc.
Synaptogenesis on mature hippocampal dendrites occurs via filopodia and immature spines during blocked synaptic transmission
Authors: Petrak Lara J. , Harris Kristen M. , Kirov Sergei A.
Published: February 2005

During development, dendritic spines emerge as stubby protrusions from single synapses on dendritic shafts or from retracting filopodia, many of which have more than one synapse. These structures are rarely encountered in the mature brain. Recently, confocal and two‐photon microscopy have revealed a proliferation of new filopodia‐like protrusions in mature hippocampal slices, especially when synaptic transmission was blocked. It was not known whether these protrusions have synapses nor whether they are accompanied by the other immature spine forms. Here, reconstruction from serial section electron microscopy (ssEM) was used to answer these questions. Acute hippocampal slices from mature male rats, ages 56 and 63 days, were maintained in vitro in control medium or in a nominally calcium‐free medium with high magnesium, glutamate receptor antagonists, and sodium and calcium channel blockers. At the end of each 8‐hour experiment, all slices were fixed, coded, and processed for ssEM. In agreement with light microscopy, there were more filopodia along dendrites in slices with blocked synaptic transmission. These filopodia were identified by their pointy tips and either the absence of synapses or presence of multiple synapses along them. There was also a proliferation of stubby spines. Filopodia along mature dendrites were typically shorter than developmental filopodia, with outgrowth likely being constrained by reduced extracellular space and compact neuropil, providing numerous candidate presynaptic partners in the vicinity of the mature dendrites. These findings suggest that synaptogenesis and spine formation are readily initiated under conditions of reduced activity in the mature brain. J. Comp. Neurol. 484:183–190, 2005. © 2005 Wiley‐Liss, Inc.
TGF‐β induces novel Lef‐1 splice variants through a Smad‐independent signaling pathway
Authors: Cordray Pauline , Satterwhite Daniel J.
Published: February 2005

The lymphoid enhancer‐binding factor (Lef‐1) transcription factor is best known for the ability to transduce Wnt signals during development and to mediate excessive Wnt signaling in certain types of cancer. We recently identified and characterized a novel Wnt‐like effect of transforming growth factor‐beta (TGF‐β) on β‐catenin, the binding partner of Lef‐1. Therefore, we sought to determine the effect of TGF‐β on expression of the Lef/T‐cell–specific transcription factor (TCF) components of the Wnt pathway. We found that TGF‐β markedly induced Lef‐1 mRNA expression in cell lines originating from fetal lung (Mv1Lu) and newborn skin (Balb/MK), tissues that normally express Lef‐1 during development. Lef‐1 induction was temporally related to but independent of TGF‐β–induced G1 cell cycle arrest. Furthermore, the induction of Lef‐1 was independent of both new protein synthesis and Smad‐mediated signaling. Using TGF‐β–treated Mv1Lu cells, we identified multiple splice forms of Lef‐1, including novel variants that lack both exons 2 and 3. We conclude that the induction of Lef‐1 has permissive effects on the well‐characterized TGF‐β signal that inhibits c‐myc expression and induces a G1 arrest. Developmental Dynamics 232:969–978, 2005. © 2005 Wiley‐Liss, Inc.
Metal‐Directed Stereoselective Syntheses of Homochiral Complexes of exo‐Bidentate Binaphthol Derivatives
Authors: Wang Ruihu , Xu Lijin , Ji Jianxin , Shi Qian , Li Yueming , Zhou Zhongyuan , Hong Maochun , Chan Albert S. C.
Published: February 2005

The homochiral exo‐bidentate ligands (S)‐2,2′‐bis(pyridylmethyleneoxy)‐1,1′‐binaphthyl [(S)‐L] and (R)‐2,2′‐bis(pyridylmethyleneoxy)‐1,1′‐binaphthyl [(R)‐L] were synthesized and employed for the preparation of coordination complexes with the aim of investigating the effect of an axially chiral 1,1′‐binaphthyl connector on self‐assembly process. Five homochiral complexes, [Ag{(S)‐L}(ClO4)]n (1), [Ag{(R)‐L}(ClO4)]n (2), [{Cd{(S)‐L}(H2O)Cl2}(H2O)0.5]n (3), [(Zn{(S)‐L}Cl2)(DMF)0.5(H2O)0.5]n (4), and [(Pd2{(S)‐L}2Cl4)(H2O)1.5]n (5), have been prepared and characterized by single‐crystal X‐ray diffraction analyses. The enantiomeric complexes 1 and 2 are isomorphous and are formed through interconnection of ligands and two‐coordinate AgI centers. Complex 3 possesses a similar structural framework to 1 and is formed with two nitrogen atoms from (S)‐L coordinating to six‐coordinate CdII in a trans mode. The interlocking in part of the adjacent, one‐dimensional helix‐like chains stabilizes its structure. Complex 4 is a one‐dimensional zigzag chain and is formed through interconnection of (S)‐L and ZnCl2 units. The exo‐bidentate (S)‐L ligand in 5 links square‐planar PdII into a homochiral dinuclear metallomacrocycle. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Editors' notes
Authors: Patton Michael Quinn , Patrizi Patricia
Published: February 2005

Editors' notes
Evaluating home visitation: A case study of evaluation at the David and Lucile Packard Foundation
Authors: Sherwood Kay E.
Published: February 2005

The David and Lucile Packard Foundation employed an evaluation‐focused grant‐making strategy over more than a decade in a particular child development service area, the home visitation approach, that illustrates, among other lessons, the management of disappointing evaluation results.
Diverse and creative uses of cases for teaching
Authors: Patton Michael Quinn
Published: February 2005

The three cases in this volume were developed so that each could be taught unto itself. This chapter suggests other uses for the broader context of evaluation teaching and training.
Stability and effectiveness against bacterial adhesion of poly(ethylene oxide) coatings in biological fluids
Authors: Roosjen Astrid , de Vries Joop , van der Mei Henny C. , Norde Willem , Busscher Henk J.
Published: February 2005

Poly(ethylene oxide) (PEO) coatings have been shown to reduce the adhesion of different microbial strains and species and thus are promising as coatings to prevent biomaterial‐centered infection of medical implants. Clinically, however, PEO coatings are not yet applied, as little is known about their stability and effectiveness in biological fluids. In this study, PEO coatings coupled to a glass substratum through silyl ether bonds were exposed for different time intervals to saliva, urine, or phosphate‐buffered saline (PBS) as a reference at 37°C. After exposure, the effectiveness of the coatings against bacterial adhesion was assessed in a parallel plate flow chamber. The coatings appeared effective against Staphylococcus epidermidis adhesion for 24, 48, and 0.5 h in PBS, urine, and saliva, respectively. Using XPS and contact‐angle measurements, the variations in effectiveness could be attributed to conditioning film formation. The overall short stability results from hydrolysis of the coupling of the PEO chains to the substratum. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater
Nitrogen metabolism during synchronous growth of Chlorella pyrenoidosa. I. Protein amino acid distribution
Authors: Hare T. A. , Schmidt R. R.
Published: February 2005

Total cellular‐N, acid soluble‐N, lipid plus chlorophyll‐N, and the levels of the individual amino acids were measured during synchronous growth of a high temperature strain, 7‐11‐05, of Chlorella pyrenoidosa. Total cellular‐N increased exponentially except for a small but reproducible deviation from log‐linearity which occurred at approximately the middle of the 14 hour synchronous growth cycle. Although the level of acid soluble‐N (as % of total cellular‐N) exhibited definite periodism during synchronous growth, the amount of nitrogen in this pool was small (approximately 4–8%). Lipid‐ plus chlorophyll‐N showed only slight fluctuations during cellular development; however, the trend followed that previously observed for phospholipid‐P. The levels of the protein amino acids were expressed on a mole‐percentage basis of the total protein amino acids. The level of most of the protein amino acids remained essentially constant during the course of synchronous growth. The levels of the basic and acidic amino acids as well as alanine exhibited more significant periodism than the other protein amino acids. The total protein amino acid‐N level comprised approximately 63% of the total cellular‐N throughout cellular development.