bluuebunny/crossref_metadata_2025 huggingface dataset:
MAXIMUM OCCUPATION NUMBER FOR COMPOSITE BOSON STATES
Authors: ROMBOUTS S. , VAN NECK D. , PEIRS K. , POLLET L.
Published: October 2002

One of the major differences between fermions and bosons is that fermionic states have a maximum occupation number of one, whereas the occupation number for bosonic states is in principle unlimited. For bosons that are made up of fermions, one could ask the question to what extent the Pauli principle for the constituent fermions would limit the boson occupation number. Intuitively one can expect the maximum occupation number to be proportional to the available volume for the bosons divided by the volume occupied by the fermions inside one boson, though a rigorous derivation of this result has not been given before. In this letter we show how the maximum occupation number can be calculated from the ground-state energy of a fermionic generalized pairing problem. A very accurate analytical estimate of this eigenvalue is derived. From that a general expression is obtained for the maximum occupation number of a composite boson state, based solely on the intrinsic fermionic structure of the bosons. The consequences for Bose–Einstein condensates of excitons in semiconductors and ultra cold trapped atoms are discussed.
fushi tarazu: A Hox gene changes its role
Authors: Damen Wim G.M.
Published: October 2002

The Hox genes play a role in anteroposterior axis specification of bilaterian animals that has been conserved for more than 600 million years. However, some of these genes have occasionally changed their roles in evolution. For example, the insect gene fushi tarazu (ftz), although localised in the Hox cluster, no longer acts as a Hox gene, but is involved in segmentation and nervous system development. Recent data of Mouchel‐Vielh et al.,1 and Hughes and Kaufman2 on ftz homologues in a crustacean and a myriapod, respectively, shed new light onto the evolution of this gene. BioEssays 24:992–995, 2002. © 2002 Wiley‐Periodicals, Inc.
Widespread organisation of C. elegans genes into operons: Fact or function?
Authors: Nimmo Rachael , Woollard Alison
Published: October 2002

A recent report by Blumenthal et al.1 provides convincing evidence that at least 15% of Caenorhabditis elegans genes are co‐transcribed within over a thousand operons. Polycistronic transcription of gene clusters is very rare in eukaryotes. The widespread occurrence of operons in C. elegans thus raises some interesting questions about the origin and function of these multigenic transcriptional units. BioEssays 24:983–987, 2002. © 2002 Wiley‐Periodicals, Inc.
TOPOLOGICAL DEFECTS AND THE TRIAL ORBIT METHOD
Authors: BAZEIA D. , FREIRE W. , LOSANO L. , RIBEIRO R. F.
Published: October 2002

We deal with the presence of topological defects in models for two real scalar fields. We comment on defects hosting topological defects and search for explicit defect solutions using the trial orbit method. As we know, under certain circumstances the second-order equations of motion can be solved by solutions of first-order differential equations. In this case we show that the trial orbit method can be used very efficiently to obtain explicit solutions.
ENUMERATION OF WHITEHEAD GROUPS OF LOW ORDER
Authors: ALP MURAT
Published: October 2002

In this paper we describe a share package of functions for computing with finite, permutation crossed modules, cat1-groups and their morphisms, written using the [Formula: see text] group theory programming language. The category XMod of crossed modules is equivalent to the category Cat1 of cat1-groups and we include functions emulating the functors between these categories. The monoid of derivations of a crossed module [Formula: see text], and the corresponding monoid of sections of a cat1-group [Formula: see text], are constructed using the Whitehead multiplication. The Whitehead group of invertible derivations, together with the group of automorphisms of X, are used to construct the actor crossed module of X which is the automorphism object in XMod. We include a table of the 350 isomorphism classes of cat1-structures on groups of order at most 30 in [2].
A Drosophila melanogaster cell line (S2) facilitates post‐genome functional analysis of receptors and ion channels
Authors: Towers Paula R. , Sattelle David B.
Published: October 2002

The complete sequencing of the genome of the fruit fly Drosophila melanogaster offers the prospect of detailed functional analysis of the extensive gene families in this genetic model organism. Comprehensive functional analysis of family members is facilitated by access to a robust, stable and inducible expression system in a fly cell line. Here we show how the Schneider S2 cell line, derived from the Drosophila embryo, provides such an expression system, with the bonus that radioligand binding studies, second messenger assays, ion imaging, patch‐clamp electrophysiology and gene silencing can readily be applied. Drosophila is also ideal for the study of new control strategies for insect pests since the receptors and ion channels that many new animal health drugs and crop protection chemicals target can be expressed in this cell line. In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. BioEssays 24:1066–1073, 2002. © 2002 Wiley‐Periodicals, Inc.
A preliminary report on the use of a Web site www.meatandhealth. com dedicated to health professionals
Authors: Strong Maureen
Published: October 2002

This paper briefly details the preliminary findings on the usage of the Web site launched by the British Meat Nutrition Education Service which is dedicated to health care professions. The way in which the Web site has been launched to state‐registered dietitians in the first instance is discussed. The uptake of the nutrition education tool entitled “Getting the balance right” available both as a poster and leaflet is briefly quantified. This tool acts as a food selection guide, which can be used by those involved in nutrition education. Details of how to obtain copies of “Getting the balance right” are included.
Nutrition and the elderly in residential care
Authors: Blades Mabel
Published: October 2002

A summary of the definitions of the age at which people are regarded as elderly and relevant demographics is given. Details of the nutritional standards for elderly people in residential care are provided. The National Minimum Standards for Care Homes for Older People published by the Department of Health in 2002 are highlighted. Information on the professional groups involved in catering for those in residential care are detailed. A discussion and recommendations are included.
New Insights into Neuron-Glia Communication
Authors: Fields R. Douglas , Stevens-Graham Beth
Published: October 2002

Two-way communication between neurons and nonneural cells called glia is essential for axonal conduction, synaptic transmission, and information processing and thus is required for normal functioning of the nervous system during development and throughout adult life. The signals between neurons and glia include ion fluxes, neurotransmitters, cell adhesion molecules, and specialized signaling molecules released from synaptic and nonsynaptic regions of the neuron. In contrast to the serial flow of information along chains of neurons, glia communicate with other glial cells through intracellular waves of calcium and via intercellular diffusion of chemical messengers. By releasing neurotransmitters and other extracellular signaling molecules, glia can affect neuronal excitability and synaptic transmission and perhaps coordinate activity across networks of neurons.
Developmental paradigms in terminal lung development
Authors: Prodhan Parthak , Kinane T. Bernard
Published: October 2002

Late lung development comprises the formation of the terminal sac followed by the subdivision of the terminal sac by septa into alveoli and results in the formation of the gas‐exchange surface of the lung. This developmentally regulated process involves a complex epithelium–mesenchyme interaction via evolutionarily conserved molecular signaling pathways. In addition, there is a continuous process of vascular growth and development. Currently there are large gaps in our understanding of the molecular mechanisms involved in the formation of the gas‐exchange surface. In this review, we attempt to integrate and reconcile the morphologic features in late lung development with what is known about the molecular basis for these processes. We describe the formation of the terminal sac and the subsequent formation of the septa, which divide the terminal sac into alveoli, in terms of the classically described developmental stages of induction, morphogenesis and differentiation. We believe that evolutionarily conserved pathways regulate this process and that morphogen gradients are likely to be a central mechanism. In addition, we highlight the importance of the molecular mechanisms involved in the simultaneous development of the vascular bed and its importance in the late development of the lungs. BioEssays 24:1052–1059, 2002. © 2002 Wiley‐Periodicals, Inc.
Bulimia nervosa following psychological and multiple child abuse: Support for the self‐medication hypothesis in a population‐based cohort study
Authors: Schoemaker Casper , Smit Filip , Bijl Rob V. , Vollebergh Wilma A. M.
Published: October 2002

Objective

To unravel the complex role of child abuse as a risk factor for bulima nervosa (BN), from the perspective of the self‐medication hypothesis which asserts that in abused BN cases binge eating is primarily a way of coping with the anxiety or mood disorders that stem from the abuse.

Method

In a population‐based study (N = 1987) DSM‐III‐R diagnoses were assessed with the CIDI. Differences in exposure rates to child abuse between BN cases versus healthy, psychiatric, substance use, and dual diagnosis controls were employed to test the self‐medication hypothesis.

Results

A history of psychological or multiple abuse was found to be a specific risk factor for dual diagnosis disorder (cases with psychiatric and substance use disorders) and for BN. Nearly all BN cases that experienced multiple or psychological child abuse, showed such comorbid anxiety or mood disorders.

Discussion

We found tentative support for the self‐medication hypothesis. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 32: 381–388, 2002.
Comparative observations on corneas, with special reference to bowman's layer and descemet's membrane in mammals and amphibians
Authors: Hayashi Shuichiro , Osawa Tokuji , Tohyama Koujiro
Published: October 2002

Corneas of tadpole, mouse, rat, guinea pig, rabbit, cat, cattle, and human were examined by TEM and SEM in a comparative study. The differences between species were noted mainly by using TEM. Bowman's layer showed a tendency to be well developed in higher mammals. Tadpoles lack a Bowman's layer, lower mammals have a thin Bowman's layer, and higher mammals have a thick Bowman's layer. The boundary between the substantia propria and Descemet's membrane was distinct in higher mammals. On the other hand, there are no differences in thickness of the collagen fibrils that constitute Bowman's layer and those of the substantia propria. NaOH digestion was utilized for SEM preparation. SEM imaging revealed a textured appearance of the epithelial side of Bowman's layer. In Descemet's membrane, fibrous long spacing (FLS) fiber‐like structures, which are arranged in parallel to the endothelium, were observed by both TEM and SEM. To our knowledge, this is the first report of SEM observations of FLS fiber‐like structures on the endothelial surface of Descemet's membrane. SEM at a plane normal to the plane of the cornea showed that Descemet's membrane has a piled laminar structure. Descemet's membrane is closely associated with the collagen layer of the substantia propria. Collagen fibrils invading from the substantia propria into Descemet's membrane were observed with both TEM and SEM. J. Morphol. 254:247–258, 2002. © 2002 Wiley‐Liss, Inc.
Organization of the male gonad in a protogynous fish, Thalassoma bifasciatum (Teleostei: Labridae)
Authors: Koulish Sasha , Kramer Charles R. , Grier Harry J.
Published: October 2002

Although the testis in teleosts has been investigated for many years, little attention has been paid to the structure of the outer layers that enclose the testis and to their possible contributions to its organization. The present study in a protogynous male labrid, Thalassoma bifasciatum (bluehead wrasse), describes the arrangement and cytology of these tissues (for convenience, referred to collectively as the outer wall, OW) which include: the outer peritoneal layer and subjacent collagen fibers, myoid cells and diverse other cells and tissues, e.g., fibrocytes, presumptive mesenchyme, macrophages, granulocytes, nerves, and blood vessels. Beneath the OW are two compartments; one is the gamete‐laden spermatocysts, the other the interstitium, which is composed of cells and tissues that lie between the spermatocysts. Both OW and interstitium contain similar kinds of tissues and cells. Moreover, the layers of the OW immediately subjacent to the peritoneum are continuous with that in the interstitium. It is suggested that the continuity between these two areas provides opportunities for the exchange of cells that could aid in the maintenance and reorganization of the testis and with the myoid and neural tissue to establish an extensive, coordinated motile system that aids movement of sperm from spermatocysts to the ducts. A recent report on the reexamination of the germinal epithelium concept and its identification in the common snook, Centropomus undecimalis, stimulated us to examine the feasibility of applying this concept to gonad organization and gamete development in T. bifasciatum. In addition, the ultrastructure of the Sertoli cell and formation of spermatocysts are described. Spermatocysts increase in size during the development of gametes. Observations and discussion are presented suggesting how Sertoli cells may accommodate this growth and how new populations of these cells may arise in the mature adult. Finally, ultrastructural characteristics for each stage of spermatogenesis are presented and, using (3H)thymidine and autoradiography, data on the chronology of spermatogonia–sperm cycle are included. J. Morphol. 254:292–311, 2002. © 2002 Wiley‐Liss, Inc.
Sequence variants in the human 25‐hydroxyvitamin D3 1‐α‐hydroxylase (CYP27B1) gene are not associated with prostate cancer risk
Authors: Hawkins Gregory A. , Cramer Scott D. , Zheng Siqun L. , Isaacs Sarah D. , Wiley Kathy E. , Chang Bao‐Li , Bleecker Eugene R. , Walsh Patrick C. , Meyers Deborah A. , Isaacs William B. , Xu Jianfeng
Published: October 2002

BACKGROUND

1,25‐dihydroxyvitamin D3 has been shown to have antiproliferative properties on normal and neoplastic prostatic cells. 25‐hydroxyvitamin D3 1‐α‐hydroxylase, the enzyme that catalyzes the final step of vitamin D synthesis, converting 25‐hydroxyvitamin D3 to 1,25‐dihydroxyvitamin D3, is expressed in the prostate.

METHODS

The human 25‐hydroxyvitamin D3 1‐α‐hydroxylase gene (CYP27B1) was resequenced in a case/control panel consisting of 64 individuals (48 Caucasians and 16 African Americans), with equal numbers of hereditary prostate cancer cases, sporadic cases, and unaffected controls. Three frequent single nucleotide polymorphisms (SNPs) were genotyped in 245 prostate cancer cases and 222 controls.

RESULTS

Six noncoding SNPs were identified in the CYP27B1 gene. No significant difference was found in allele and genotype frequencies between sporadic cases and unaffected controls for the three genotyped SNPs.

CONCLUSION

This study suggests that the CYP27B1 gene does not play a major role as a prostate cancer susceptibility gene. Prostate 53: 175–178, 2002. © 2002 Wiley‐Liss, Inc.
Klava: a Java package for distributed and mobile applications
Authors: Bettini Lorenzo , De Nicola Rocco , Pugliese Rosario
Published: October 2002

Highly distributed networks have now become a common infrastructure for wide‐area distributed applications whose key design principle is network awareness, namely the ability to deal with dynamic changes of the network environment. Network‐aware computing has called for new programming languages that exploit the mobility paradigm as a basic interaction mechanism. In this paper we present the architecture of KLAVA, an experimental Java package for distributed applications and code mobility. We describe how KLAVA permits code mobility by relying on Java and present a few distributed applications that exploit mobile code programmed in KLAVA. Copyright © 2002 John Wiley & Sons, Ltd.
VaR
Authors: Pearson Neil D. , Smithson Charles
Published: October 2002

Since “Value at Risk” (VaR) received its first wide introduction in the July 1993 Group of Thirty report, the number of users of—and uses for—VaR have increased dramatically. However, VaR itself has been evolving. In this article, we will first review some of the important refinements in VaR that have appeared—improved speed of computation, improved accuracy, and improved stress testing. We then look at the “next steps” (which we refer to as “Beyond VaR”), in which we review extensions to standard VaR, the emergence of “risk contribution” measures, and alternatives to standard VaR (including Extreme Value Theory [EVT] and Coherent Risk Measures).
Global portfolios should be optimized in excess, not total returns
Authors: Norland Erik , Wilford D.Sykes
Published: October 2002

When constructing portfolios, practitioners must take opportunity cost into account and view returns as excess, not total returns. Using total returns in a means–variance optimization—a remarkably common error—introduces a bias that will cause “optimal” portfolios to overweight domestic cash securities at the expense of higher‐risk instruments and instruments invested abroad. The original work on modern portfolio theory made little mention of excess versus total returns in optimization in part because the theory assumed one was only choosing between risky assets and that all of the assets were denominated in the same currency. Thus, those who refer to the original version of the theory could easily misapply it when considering assets in different currency zones. This paper seeks to demonstrate the problems and biases inherent in using total returns versus excess returns in means–variance optimization.
Urban Productivity in China
Authors: Pan Zuohong , Zhang Fan
Published: October 2002

In this empirical study, we test the relationship of Chinese urban productivity and city size. Using over 119 790 firm-level production data cross 28 industries from the Third National Industrial Survey, along with the urban population data of 224 cities, we find strong and prevailing significant agglomeration economies in Chinese urban areas. The estimated average agglomeration elasticity is around 0.051, implying that every doubling of city size will provide a 3.6 per cent gain in firm productivity. The breakdown analysis suggests that, based on current data, the major source of the agglomeration advantage comes from localisation economies-benefits from the concentration of firms of the same industry within one geographical area-rather than urbanisation economies-externalities from urban development itself. The maximum size study also suggests that, while most Chinese cities have yet to grow to demonstrate the full strength of agglomeration economies, many Chinese industries have reached the 'optimal' industry size within a 'given' urban area.
The Belgian PCB/Dioxin Incident: A Critical Review of Health Risks Evaluations
Authors: Bernard A. , Fierens S.
Published: October 2002

The Belgian PCB/dioxin incident is a food contamination that occurred in Belgium in January 1999 when a tank of recycled fats used to produce animal feeds was accidentally contaminated by approximately 100 L of polychlorinated biphenyl (PCB) oil containing 50 kg PCBs expressed as the sum of the seven markers, 1 g (TEQ) dioxins (PCDD/Fs) and 2 g toxic equivalent (TEQ) dioxin-like PCBs. The incident was discovered when a poultry poisoning resembling the classic chick edema disease broke out in several farms that had received contaminated feeds. The delay in making public this incident resulted in a major political and food crisis and caused much concern in the population. We review here the health risk evaluations that were made after this incident and we assess the likelihood of the different scenarios by taking into account recent data on the real scale of the contamination and on the dioxin body burden of the general population in Belgium. These new data confirm that the incident was too limited in time and in scale to have increased the PCB/dioxin body burden of the general population at large, a conclusion supported by a survey of dioxin levels in blood conducted at the end of 1999. Only farmers in poultry farms affected by the incident (about 30 farms) and having regularly consumed their own products could have increased their PCB/dioxin body burden. It is unlikely, however, that these farmers could have increased their PCB/dioxin body burden above levels prevailing in the 1980s or now found in communities regularly consuming seafood.
Can We Protect Everybody from Drinking Water Contaminants?
Authors: Howd Robert A.
Published: October 2002

Dozens of chemicals, both natural and manmade, are often found in drinking water. Some, such as the natural contaminants uranium and arsenic, are well-known toxicants with a large toxicology database. Other chemicals, such as methyl tertiary-butyl ether (MTBE) from leaking fuel tanks, we learn about as we go along. For still others, such as the alkyl benzenes, there are very little available data, and few prospects of obtaining more. In some cases, chemicals are purposely added to drinking water for beneficial purposes (e.g., chlorine, fluoride, alum), which may cause a countervailing hazard. Removing all potentially toxic chemicals from the water is virtually impossible and is precluded for beneficial uses and for economic reasons. Determination of safe levels of chemicals in drinking water merges the available toxicity data with exposure and human effect assumptions into detailed hazard assessments. This process should incorporate as much conservatism as is needed to allow for uncertainty in the toxicity and exposure estimates. Possible sensitive subpopulations such as unborn children, infants, the elderly, and those with common diseases such as impaired kidney function must also be considered. However, the range of sensitivity and the variability of toxicity and exposure parameters can never be fully documented. In addition, the validity of the low-dose extrapolations, and whether the toxic effect found in animals occurs at all in humans, is never clear. This publication discusses how these competing needs and uncertainties intersect in the development of Public Health Goals for uranium, fluoride, arsenic, perchlorate, and other highly debated chemicals.
Caveolin-1-deficient Mice Show Accelerated Mammary Gland Development During Pregnancy, Premature Lactation, and Hyperactivation of the Jak-2/STAT5a Signaling Cascade
Authors: Park David S. , Lee Hyangkyu , Frank Philippe G. , Razani Babak , Nguyen Andrew V. , Parlow Albert F. , Russell Robert G. , Hulit James , Pestell Richard G. , Lisanti Michael P.
Published: October 2002

It is well established that mammary gland development and lactation are tightly controlled by prolactin signaling. Binding of prolactin to its cognate receptor (Prl-R) leads to activation of the Jak-2 tyrosine kinase and the recruitment/tyrosine phosphorylation of STAT5a. However, the mechanisms for attenuating the Prl-R/Jak-2/STAT5a signaling cascade are just now being elucidated. Here, we present evidence that caveolin-1 functions as a novel suppressor of cytokine signaling in the mammary gland, akin to the SOCS family of proteins. Specifically, we show that caveolin-1 expression blocks prolactin-induced activation of a STAT5a-responsive luciferase reporter in mammary epithelial cells. Furthermore, caveolin-1 expression inhibited prolactin-induced STAT5a tyrosine phosphorylation and DNA binding activity, suggesting that caveolin-1 may negatively regulate the Jak-2 tyrosine kinase. Because the caveolin-scaffolding domain bears a striking resemblance to the SOCS pseudosubstrate domain, we examined whether Jak-2 associates with caveolin-1. In accordance with this homology, we demonstrate that Jak-2 cofractionates and coimmunoprecipitates with caveolin-1. We next tested the in vivo relevance of these findings using female Cav-1 (−/−) null mice. If caveolin-1 normally functions as a suppressor of cytokine signaling in the mammary gland, then Cav-1 null mice should show premature development of the lobuloalveolar compartment because of hyperactivation of the prolactin signaling cascade via disinhibition of Jak-2. In accordance with this prediction, Cav-1 null mice show accelerated development of the lobuloalveolar compartment, premature milk production, and hyperphosphorylation of STAT5a (pY694) at its Jak-2 phosphorylation site. In addition, the Ras-p42/44 MAPK cascade is hyper-activated. Because a similar premature lactation phenotype is observed in SOCS1 (−/−) null mice, we conclude that caveolin-1 is a novel suppressor of cytokine signaling.
Subcellular Recruitment of Fibrillarin to Nucleoplasmic Proteasomes: Implications for Processing of a Nucleolar Autoantigen
Authors: Chen Min , Rockel Thomas , Steinweger Gabriele , Hemmerich Peter , Risch Jakob , von Mikecz Anna
Published: October 2002

A prerequisite for proteins to interact in a cell is that they are present in the same intracellular compartment. Although it is generally accepted that proteasomes occur in both, the cytoplasm and the nucleus, research has been focusing on cytoplasmic protein breakdown and antigen processing, respectively. Thus, little is known on the functional organization of the proteasome in the nucleus. Here we report that within the nucleus 20S and 26S proteasomes occur throughout the nucleoplasm and partially colocalize with splicing factor–containing speckles. Because proteasomes are absent from the nucleolus, a recruitment system was used to analyze the molecular fate of nucleolar protein fibrillarin: Subtoxic concentrations of mercuric chloride (HgCl2) induce subcellular redistribution of fibrillarin and substantial colocalization (33%) with nucleoplasmic proteasomes in different cell lines and in primary cells isolated from mercury-treated mice. Accumulation of fibrillarin and fibrillarin-ubiquitin conjugates in lactacystin-treated cells suggests that proteasome-dependent processing of this autoantigen occurs upon mercury induction. The latter observation might constitute the cell biological basis of autoimmune responses that specifically target fibrillarin in mercury-mouse models and scleroderma.
Genetic Analysis of Sorting Nexins 1 and 2 Reveals a Redundant and Essential Function in Mice
Authors: Schwarz Dana Gilbert , Griffin Courtney T. , Schneider Elizabeth A. , Yee Della , Magnuson Terry
Published: October 2002

Sorting nexins 1 (Snx1) and 2 (Snx2) are homologues of the yeast gene VPS5 that is required for proper endosome-to-Golgi trafficking. The prevailing thought is that Vps5p is a component of a retrograde trafficking complex called the retromer. Genetic and biochemical evidence suggest mammals may have similar complexes, but their biological role is unknown. Furthermore, if SNX1 and SNX2 belong to such complexes, it is not known whether they act together or separately. Herein, we show that mice lacking SNX1 or SNX2 are viable and fertile, whereas embryos deficient in both proteins arrest at midgestation. These results demonstrate that SNX1 and SNX2 have a highly redundant and necessary function in the mouse. The phenotype ofSnx1-/-;Snx2-/-embryos is very similar to that of embryos lacking another retromer homologue, Hβ58. This finding suggests that SNX1/SNX2 and Hβ58 function in the same genetic pathway, providing additional evidence for the existence of mammalian complexes that are structurally similar to the yeast retromer. Furthermore, the viability ofSnx1-/-andSnx2-/-mice demonstrates that it is not necessary for SNX1 and SNX2 to act together. Electron microscopy indicates morphological alterations of apical intracellular compartments in theSnx1-/-;Snx2-/-yolk-sac visceral endoderm, suggesting SNX1 and SNX2 may be required for proper cellular trafficking. However, tetraploid aggregation experiments suggest that yolk sac defects cannot fully account forSnx1-/-; Snx2-/-embryonic lethality. Furthermore, endocytosis of transferrin and low-density lipoprotein is unaffected in mutant primary embryonic fibroblasts, indicating that SNX1 and SNX2 are not essential for endocytosis in all cells. Although the two proteins demonstrate functional redundancy,Snx1+/-;Snx2-/-mice display abnormalities not observed inSnx1-/-;Snx2+/-mice, revealing that SNX1 and SNX2, or their genetic regulation, are not equivalent. Significantly, these studies represent the first mutations in the mammalian sorting nexin gene family and indicate that sorting nexins perform essential functions in mammals.
Geminin Deficiency Causes a Chk1-dependent G2 Arrest inXenopus
Authors: McGarry Thomas J.
Published: October 2002

Geminin is an unstable inhibitor of DNA replication that gets destroyed at the metaphase/anaphase transition. The biological function of geminin has been difficult to determine because it is not homologous to a characterized protein and has pleiotropic effects when overexpressed. Geminin is thought to prevent a second round of initiation during S or G2 phase. In some assays, geminin induces uncommitted embryonic cells to differentiate as neurons. In this study, geminin was eliminated from developing Xenopus embryos by using antisense techniques. Geminin-deficient embryos show a novel and unusual phenotype: they complete the early cleavage divisions normally but arrest in G2 phase immediately after the midblastula transition. The arrest requires Chk1, the effector kinase of the DNA replication/DNA damage checkpoint pathway. The results indicate that geminin has an essential function and that loss of this function prevents entry into mitosis by a Chk1-dependent mechanism. Geminin may be required to maintain the structural integrity of the genome or it may directly down-regulate Chk1 activity. The data also show that during the embryonic cell cycles, rereplication is almost entirely prevented by geminin-independent mechanisms.
Novel Proteins Linking the Actin Cytoskeleton to the Endocytic Machinery inSaccharomyces cerevisiae
Authors: Dewar H. , Warren D. T. , Gardiner F. C. , Gourlay C. G. , Satish N. , Richardson M. R. , Andrews P. D. , Ayscough K. R.
Published: October 2002

The importance of coupling the process of endocytosis to factors regulating actin dynamics has been clearly demonstrated in yeast, and many proteins involved in these mechanisms have been identified and characterized. Here we demonstrate the importance of two additional cortical components, Ysc84p and Lsb5p, which together are essential for the organization of the actin cytoskeleton and for fluid phase endocytosis. Both Ysc84p and Lsb5p were identified through two-hybrid screens with different domains of the adaptor protein Sla1p. Ysc84p colocalizes with cortical actin and requires the presence of an intact actin cytoskeleton for its cortical localization. Ycl034w/Lsb5p localizes to the cell cortex but does not colocalize with actin. The Lsb5 protein contains putative VHS and GAT domains as well as an NPF motif, which are all domains characteristic of proteins involved in membrane trafficking. Deletion of either gene alone does not confer any dramatic phenotype on cells. However, deletion of both genes is lethal at elevated temperatures. Furthermore, at all temperatures this double mutant has depolarized actin and an almost undetectable level of fluid phase endocytosis. Our data demonstrate that Ysc84p and Lsb5p are important components of complexes involved in overlapping pathways coupling endocytosis with the actin cytoskeleton in yeast.
Effect of roselle (Hibiscus sabdariffa L.) on serum lipids of Sprague Dawley rats
Authors: Tee Pau‐Ling , Yusof Salmah , Mohamed Suhaila , Aimi Umar Nor , Mohamed Mustapha Noordin
Published: October 2002

The efficacy of roselle as a functional food has been revealed lately, especially for its antioxidant bioactivity. In this study, the benefits of roselle were further studied in vivo using the model of male Sprague Dawley rats fed with normal diets (C), 2.5 percent roselle (R), 2.5 percent roselle with 15 percent soybean oil (RO) and 15 percent soybean oil (O) for 25 weeks. The results demonstrated that supplementation of roselle in the diets significantly (p < 0.05) reduced the gross body weight and increased the high‐density lipoproteins cholesterol (HDL‐C) compared to the rats fed with normal diets and oil diets, and reduced the level of triglycerides in the serum. Serum total cholesterol of R group decreased compared to C but increased in RO compared to O group. Significant increase (p < 0.05) of serum uric acid was observed in R group at week 15 and 20. Addition of roselle in oil diet significantly decreased (p < 0.05) the malondialdehyde formation at week 20 and 25 but there was no significant effect of roselle on the catalase activity among the treatments at all time points. Suggests that roselle might play a role in the prevention of atherosclerosis and obesity.
Role of Predicted Metalloprotease Motif of Jab1/Csn5 in Cleavage of Nedd8 from Cul1
Authors: Cope Gregory A. , Suh Greg S. B. , Aravind L. , Schwarz Sylvia E. , Zipursky S. Lawrence , Koonin Eugene V. , Deshaies Raymond J.
Published: October 2002

COP9 signalosome (CSN) cleaves the ubiquitin-like protein Nedd8 from the Cul1 subunit of SCF ubiquitin ligases. The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity. JAMM is found in proteins from archaea, bacteria, and eukaryotes, including the Rpn11 subunit of the 26
S
proteasome. Metal chelators and point mutations within JAMM abolished CSN-dependent cleavage of Nedd8 from Cul1, yet had little effect on CSN complex assembly. Optimal SCF activity in yeast and both viability and proper photoreceptor cell (R cell) development in
Drosophila melanogaster
required an intact Csn5 JAMM domain. We propose that JAMM isopeptidases play important roles in a variety of physiological pathways.
A MILLENNIUM PROJECT: CONSTRUCTING SMALL GROUPS
Authors: BESCHE HANS ULRICH , EICK BETTINA , O'BRIEN E. A.
Published: October 2002

We survey the problem of constructing the groups of a given finite order. We provide an extensive bibliography and outline practical algorithmic solutions to the problem. Motivated by the millennium, we used these methods to construct the groups of order at most 2000; we report on this calculation and describe the resulting group library.
FIXED POINTS OF SYMMETRIC ENDOMORPHISMS OF GROUPS
Authors: SYKIOTIS MIHALIS
Published: October 2002

Let G be the fundamental group of a graph of groups with finite edge groups and f an endomorphism of G. We prove a structure theorem for the subgroup Fix(f), which consists of the elements of G fixed by f, in the case where the endomorphism f of G maps vertex groups into conjugates of themselves.
Vitamin D
3
–Upregulated Protein-1 (VDUP-1) Regulates Redox-Dependent Vascular Smooth Muscle Cell Proliferation Through Interaction With Thioredoxin
Authors: Schulze P. Christian , De Keulenaer Gilles W. , Yoshioka Jun , Kassik Kimberly A. , Lee Richard T.
Published: October 2002

Reactive oxygen species are important cellular signaling molecules, and thioredoxin (TRX) is a key regulator of cellular redox balance. We investigated the interaction of TRX with its endogenous inhibitor, vitamin D
3
–upregulated protein (VDUP)-1, in human aortic smooth muscle cells (SMCs). Adenoviral gene transfer of TRX enhanced TRX enzyme activity 2.7±0.4-fold (
P
<0.05 versus cells infected with adenoviral vector expressing green fluorescent protein [AdGFP]) and resulted in a 3.8±0.5-fold increase of cellular DNA synthesis as detected by methyl-[
3
H]thymidine incorporation (
P
<0.001). Platelet-derived growth factor (PDGF) also increased TRX enzyme activity 2.5±3.3-fold (
P
<0.05 versus no stimulation) and DNA synthesis 6.5±0.3-fold (
P
<0.001 versus no stimulation) without significant changes in TRX expression. PDGF and H
2
O
2
time-dependently suppressed VDUP-1 expression (13-fold and 30-fold reduction after 1 hour, respectively;
P
<0.001), and this was inhibited by the cell-permeable antioxidants
N
-acetylcysteine and 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron). Overexpression of VDUP-1 (AdVDUP-1) reduced TRX activity at baseline (−61±23% versus control cells,
P
<0.05) and abolished PDGF-induced TRX activity (−9±27% in AdVDUP-1–infected cells;
P
=NS versus control cells). In addition, overexpression of VDUP-1 blocked PDGF-induced DNA synthesis (1.3±0.4-fold increase in AdVDUP-1–infected cells versus 6.5±0.4-fold increase in AdGFP-infected cells,
P
<0.001). In conclusion, VDUP-1 has marked antiproliferative effects in SMCs through the suppression of TRX activity, suggesting that the regulation of VDUP-1 is a critical molecular switch in the transduction of pro-oxidant mitogenic signals. These data also demonstrate that activation of the reductase TRX plays a pivotal role in the redox-dependent proliferation of SMCs.
Progressive Increases in Complexity of T-Wave Oscillations Herald Ischemia-Induced Ventricular Fibrillation
Authors: Nearing Bruce D. , Verrier Richard L.
Published: October 2002

T-wave alternans (TWA), an ABAB oscillation, has been postulated as the initial pattern in a stepwise progression to higher-order oscillations, culminating in sudden arrhythmic death. The present study is the first to provide experimental evidence to support this intriguing concept. Epicardial and endocardial ECGs from 12 dogs were monitored during 8-minute left anterior descending coronary artery occlusion with right atrial pacing at 150 bpm. TWA magnitude was measured by modified moving average beat analysis, and the complexity of T-wave oscillations was assessed by complex demodulation. In 6 animals with subsequent ventricular fibrillation (VF), TWA achieved a threshold of 5.00±1.30 mV in epicardial ischemic-zone electrograms, which then exhibited a stepwise increase in T-wave oscillation complexity to quadrupling (ABCDABCD, 3 cases) or tripling (ABCABC, 2 cases) and to more complex forms (5 cases) preceding VF (6 cases). In dogs without VF, peak TWA levels did not increase from baseline, measuring a maximum of 0.35±0.10 mV (
P
=NS), or only 7% the value of those with VF, and T-wave multupling was not observed (0 of 6 versus 5 of 6,
P
<0.005). Discordant TWA episodes, with T waves alternating out of phase, were associated with increased T-wave complexity and fibrillation in 4 of 6 dogs with VF but in none of the 6 dogs without VF (
P
<0.025). TWA appears to be the first step in an orderly progression of T-wave complexity, episodes of discordant TWA, and VF. This demonstrated increase in T-wave complexity points to a fundamental mechanistic link underlying the ability of TWA to predict lethal arrhythmias.
High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes
Authors: Kehat Izhak , Gepstein Amira , Spira Alon , Itskovitz-Eldor Joseph , Gepstein Lior
Published: October 2002

The goal of the present report was to establish a new in vitro model for the study of impulse propagation in human cardiac tissue. By using the human embryonic stem cell differentiating system, spontaneously contracting areas were generated in three-dimensional differentiating cell aggregates (embryoid bodies). Morphological analysis revealed an isotropic tissue of early-stage cardiac phenotype. Gap junctions, assessed by immunostaining of connexin43 and connexin45, were distributed along the cell borders. High-resolution activation maps demonstrated the presence of a functional syncytium with stable focal activation and conduction properties. Conduction was significantly slower in narrow bands of contracting tissue compared with broad cardiomyocyte regions. Establishment of this unique in vitro human model may be used for the assessment of long-term structure-function relationships, for pharmacological studies, for tissue engineering, and may permit the study of genetically modified cardiomyocytes.
Osteoporosis in the rheumatic disease patient
Authors: Lane N E , Rehman Q
Published: October 2002

Rheumatic disease patients often have both systemic and localized inflammatory processes. The result of this inflammation is tissue destruction and this translates into bone loss. Recent studies have highlighted the importance of systemic factors that either directly or indirectly activate receptor activator of nuclear factor-kB ligand (RANKL) dependent osteoclast activation and induce bone loss. In this article we will review the pathogenesis of inflammatory bone loss and explore the possible interventions to prevent it.
Identification, characterization, and cloning of an immunoglobulin degrading enzyme in the cat flea, Ctenocephalides felis
Authors: Silver Gary M. , Gaines Patrick J. , Hunter Shirley W. , Maddux Joely D. , Thomas Rex E. , Wisnewski Nancy
Published: October 2002

The degradation of cat immunoglobulin G (IgG) in blood‐fed adult C. felis midguts was examined. SDS‐PAGE analysis of dissected midgut extracts obtained from C. felis that had been blood fed for various times between 0 to 44 h revealed that by 24 h most of the high molecular weight proteins, including the heavy chain of IgG, were digested. A 31‐kDa serine protease with IgG degrading activity was purified from fed C. felis midguts by benzamidine affinity chromatography, hydrophobic interaction chromatography, and cation exchange chromatography. Three primary cleavage products between 30‐ and 40‐kDa were observed when the purified protease was incubated with protein A purified cat IgG. N‐terminal amino acid sequence analysis of the products revealed that the IgG degrading protease cleaves after specific cysteine and lysine residues within the hinge region of IgG. The enzyme is also capable of degrading other immunoglobulins, serum albumin, and hemoglobin, suggesting that it may have roles in both combating the host’s immune system and providing nutrients for the flea. A cDNA clone encoding the 265 amino acid IgG degrading protease proenzyme was isolated. When expressed in a baculovirus/insect cell expression system, the recombinant protein had the same N‐terminus as the processed 237 amino acid mature native protein and possessed IgG degrading activity indistinguishable from the native protein. Arch. Insect Biochem. Physiol. 51:136–150, 2002. © 2002 Wiley‐Liss, Inc.
Economic significance of risk premiums in the S&P 500 option market
Authors: Balyeat R. Brian
Published: October 2002

Option pricing is complicated by the theoretical existence of risk premiums. This article utilizes a testable
methodology to extract the pricing impact resulting from these risk premiums. First, option prices (based on
the full dynamics of the underlying) are computed under the assumption that these risk premiums are not
priced. The pricing methodology is independent of any particular option‐pricing model or distributional
assumptions on the return process for the underlying. The difference between the actual market prices and these
“no‐premium base case” prices reflects the effect of risk premiums. For
at‐the‐money, 13‐week S&P 500 options trading from 1989 until 1993, the effect of risk
premiums is statistically significant and averages slightly over 20% (in units of Black–Scholes
implied volatility). A simple delta‐hedging strategy is used to demonstrate the economic significance
of risk premiums, as the trading strategy provides enough profit to absorb a crash similar in magnitude to the
1987 crash once every 6.20 years. © 2002 Wiley Periodicals, Inc. Jrl Fut Mark 22:1147–1178, 2002
Sexual dimorphism and seasonal variation in submandibular gland histology of Bolomys lasiurus (rodentia, muridae)
Authors: Cangussu S.D. , Vieira F.G. , Rossoni R.B.
Published: October 2002

Wild rodents (Bolomys lasiurus) of both sexes were caught in a cerrado grassland area during the dry (July–September) and rainy (January–March) seasons of Brazil. Fasted animals were perfused with Karnovsky fixative through the left ventricle, under ether anesthesia, and the submandibular gland was processed for embedding in historesin. Histological and histometric data show sexual dimorphism at both seasons. In the volume percentage of the granular convoluted tubules (GCT) and their secretory granules, the males exhibited higher values. The absolute volume occupied by these structures, however, was dimorphic only in the rainy season. The diameter of the GCT, the height of its epithelium, and its total length were also greater in males during the rainy season. The absolute volumes of the acini and of the ductal tree were identical in both sexes in the dry and rainy seasons but the acinar diameter increased in the males and females during the rainy season. The sexual dimorphism and the seasonal variations now described in the B. lasiurus submandibular glands could be explained by the augmented reproductive activity of the males in the rainy period. J. Morphol. 254:320–327, 2002. © 2002 Wiley‐Liss, Inc.
Ultrastructure of the secretion of prostasomes from benign and malignant epithelial cells in the prostate
Authors: Sahlén Göran E. , Egevad Lars , Ahlander Anders , Norlén Bo Johan , Ronquist Gunnar , Nilsson B. Ove
Published: October 2002

BACKGROUND

Prostate epithelial cells are producing, among other things, a fluid secretion containing small bodies, the prostasomes. The mechanism of synthesis of the prostasomes is not known in details, neither is it known whether the mode of prostasome production changes at a neoplastic transformation of the prostate cells. Due to the small size of the prostasomes, we have used electron microscopy for evaluating the production and distribution of prostasomes in benign and neoplastic cells of the prostate.

METHODS

Benign and neoplastic areas in plastic embedded core biopsy specimens of prostate tissue were identified, and secreting cells were selected. The corresponding areas on the plastic blocks were further processed for examination in the electron microscope.

RESULTS

The electron microscopical examination showed that the secretory machinery was similar in both types of tissue. Thus, in both benign and well‐differentiated neoplastic cells studied, the formation of storage vesicles in the Golgi areas was similar, the content of the vesicles appeared similar, the structure and distribution of prostasomes were alike, and in both benign and malignant tissue, the secretion in the gland ducts showed the same appearance with many prostasomes.

CONCLUSION

We conclude that cells in benign prostate tissue and cells in well‐differentiated prostate carcinoma show great similarities in synthesis, storage, and release of prostasomes. However, this does not exclude the presence of other changes, for instance biochemical ones, in the prostasomes. Prostate 53: 192–199, 2002. © 2002 Wiley‐Liss, Inc.