bluuebunny/crossref_metadata_2025 huggingface dataset:
Different patterns of evolution for duplicated DNA repair genes in bacteria of the Xanthomonadales group
Authors: Martins-Pinheiro Marinalva , Galhardo Rodrigo S , Lage Claudia , Lima-Bessa Keronninn M , Aires Karina A , Menck Carlos FM
Published: September 2004

Background

DNA repair genes encode proteins that protect organisms against genetic damage generated by environmental agents and by-products of cell metabolism. The importance of these genes in life maintenance is supported by their high conservation, and the presence of duplications of such genes may be easily traced, especially in prokaryotic genomes.

Results

The genome sequences of two Xanthomonas species were used as the basis for phylogenetic analyses of genes related to DNA repair that were found duplicated. Although 16S rRNA phylogenetic analyses confirm their classification at the basis of the gamma proteobacteria subdivision, differences were found in the origin of the various genes investigated. Except for lexA, detected as a recent duplication, most of the genes in more than one copy are represented by two highly divergent orthologs. Basically, one of such duplications is frequently positioned close to other gamma proteobacteria, but the second is often positioned close to unrelated bacteria. These orthologs may have occurred from old duplication events, followed by extensive gene loss, or were originated from lateral gene transfer (LGT), as is the case of the uvrD homolog.

Conclusions

Duplications of DNA repair related genes may result in redundancy and also improve the organisms' responses to environmental challenges. Most of such duplications, in Xanthomonas, seem to have arisen from old events and possibly enlarge both functional and evolutionary genome potentiality.
Chronic arthritis in children and adolescents in two Indian health service user populations
Authors: Mauldin Joyce , Cameron H Dan , Jeanotte Diane , Solomon Glenn , Jarvis James N
Published: September 2004

Background

High prevalence rates for rheumatoid arthritis, spondyloarthopathies, and systemic lupus erythematosus have been described in American Indian and Alaskan Native adults. The impact of these diseases on American Indian children has not been investigated.

Methods

We used International Classification of Diseases-9 (ICD-9) codes to search two Indian Health Service (IHS) patient registration databases over the years 1998–2000, searching for individuals 19 years of age or younger with specific ICD-9-specified diagnoses. Crude estimates for disease prevalence were made based on the number of individuals identified with these diagnoses within the database.

Results

Rheumatoid arthritis (RA) / juvenile rheumatoid arthritis (JRA) was the most frequent diagnosis given. The prevalence rate for JRA in the Oklahoma City Area was estimated as 53 per 100,000 individuals at risk, while in the Billings Area, the estimated prevalence was nearly twice that, at 115 per 100,000. These rates are considerably higher than those reported in the most recent European studies.

Conclusion

Chronic arthritis in childhood represents an important, though unrecognized, chronic health challenge within the American Indian population living in the United States.
Enhanced diagnostic immunofluorescence using biopsies transported in saline
Authors: Vodegel Robert M , de Jong Marcelus CJM , Meijer Hillegonda J , Weytingh Marijn B , Pas Hendri H , Jonkman Marcel F
Published: September 2004

Background

The demonstration of tissue-bound immunoreactants by direct immunofluorescence microscopy (DIF) is a valuable parameter in the diagnosis of various autoimmune and immunecomplex-mediated skin diseases. For preservation of tissue-bound immunoreactants, biopsies are usually fresh-frozen in liquid nitrogen or transported in Michel's fixative. But even optimally preserved tissue specimens are no guarantee for the correct diagnosis by DIF, especially when weak to moderate IgG fluorescence of the epidermal basement membrane zone is involved. In such cases false negative results are easily obtained due to the relatively high dermal "background" fluorescence produced by polyclonal anti-human IgG fluorescein conjugates.

Methods

In the present study we have compared the use of normal saline (0.9% NaCl) with liquid nitrogen and Michel's fixative as transport medium for skin biopsies. From 25 patients with an autoimmune skin disease (pemphigus, pemphigoid, lupus erythematosus and vasculitis) four matched skin biopsies were obtained and transported in either saline for 24 and 48 hours, liquid nitrogen, or Michel's fixative for 48 hours.

Results

Direct IF microscopy showed significant reduction of background fluorescence (p < 0.01) and relatively enhanced desired specific (IgG, IgA) staining in biopsies transported in saline. A conclusive or tentative IF diagnosis was reached in 92% after 24 h saline, 83% after 48 h saline, 68% after freezing in liquid nitrogen, and 62% after 48 h Michel's medium (n = 25).

Conclusions

We conclude that transporting biopsies without freezing in normal saline for 24 hours is an adequate and attractive method for routine IF diagnosis in autoimmune and immune complex-mediated dermatoses. The superior results with saline incubation are explained by washing away of IgG background in dermis and epidermis.
Seasonal ovulatory activity exists in tropical Creole female goats and Black Belly ewes subjected to a temperate photoperiod
Authors: Chemineau Philippe , Daveau Agnès , Cognié Yves , Aumont Gilles , Chesneau Didier
Published: September 2004

Background

Seasonality of ovulatory activity is observed in European sheep and goat breeds, whereas tropical breeds show almost continuous ovulatory activity. It is not known if these tropical breeds are sensitive or not to temperate photoperiod. This study was therefore designed to determine whether tropical Creole goats and Black-Belly ewes are sensitive to temperate photoperiod. Two groups of adult females in each species, either progeny or directly born from imported embryos, were used and maintained in light-proof rooms under simulated temperate (8 to 16 h of light per day) or tropical (11 – 13 h) photoperiods. Ovulatory activity was determined by blood progesterone assays for more than two years. The experiment lasted 33 months in goats and 25 months in ewes.

Results

Marked seasonality of ovulatory activity appeared in the temperate group of Creole female goats. The percentage of female goats experiencing at least one ovulation per month dramatically decreased from May to September for the three years (0%, 27% and 0%, respectively). Tropical female goats demonstrated much less seasonality, as the percentage of goats experiencing at least one ovulation per month never went below 56%. These differences were significant.

Both groups of temperate and tropical Black-Belly ewes experienced a marked seasonality in their ovulatory activity, with only a slightly significant difference between groups. The percentage of ewes experiencing at least one ovulation per month dropped dramatically in April and rose again in August (tropical ewes) or September (temperate ewes). The percentage of ewes experiencing at least one ovulation per month never went below 8% and 17% (for tropical and temperate ewes respectively) during the spring and summer months.

Conclusions

An important seasonality in ovulatory activity of tropical Creole goats was observed when females were exposed to a simulated temperate photoperiod. An unexpected finding was that Black-Belly ewes and, to a lesser extent, Creole goats exposed to a simulated tropical photoperiod also showed seasonality in their ovulatory activity. Such results indicate that both species are capable of showing seasonality under the photoperiodic changes of the temperate zone even though they do not originate from these regions.
The medical care of patients with primary care home nursing is complex and influenced by non-medical factors: a comprehensive retrospective study from a suburban area in Sweden
Authors: Modin Sonja , Furhoff Anna-Karin
Published: September 2004

Background

The reduced number of hospital beds and an ageing population have resulted in growing demands for home nursing. We know very little about the comprehensive care of these patients. The objectives were to identify the care, in addition to primary health care, of patients with primary-care home nursing to give a comprehensive view of their care and to investigate how personal, social and functional factors influence the use of specialised medical care.

Methods

One-third (158) of all patients receiving primary-care home nursing in an area were sampled, and 73 % (116) were included. Their care from October 1995 until October 1996 was investigated by sending questionnaires to district nurses and home-help providers and by collecting retrospective data from primary-care records and official statistics. We used non-parametric statistical methods, i.e. medians and minimum – maximum, χ2, and the Mann-Whitney test, since the data were not normally distributed. Conditional logistic regression was used to study whether personal, social or functional factors influenced the chance (expressed as odds ratio) that study patients had made visits to or had received inpatient care from specialised medical care during the study year.

Results

56 % of the patients had been hospitalised. 73 % had made outpatient visits to specialised medical care. The care took place at 14 different hospitals, and more than 22 specialities were involved, but local care predominated. Almost all patients visited doctors, usually in both primary and specialised medical care. Patients who saw doctors in specialised care had more help from all other categories of care. Patients who received help from their families made more visits to specialised medical care and patients with severe ADL dependence made fewer visits.

Conclusions

The care of patients with primary-care home nursing is complex. Apart from home nursing, all patients also made outpatient visits to doctors, usually in both primary and specialised medical care. Many different caregivers and professions were involved. Reduced functional capacity decreased and help from family members increased the chance of having received outpatient specialised medical care. This raises questions concerning the medical care for patients with both medical and functional problems.
Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running
Authors: Zhu Hao , Sun Yan , Rajagopal Gunaretnam , Mondry Adrian , Dhar Pawan
Published: September 2004

Background

Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level.

Methods

We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG.

Results

We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given.

Conclusions

Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods described.
Combination of contrast with stress echocardiography: A practical guide to methods and interpretation
Authors: Moir Stuart , Marwick Thomas H
Published: September 2004

Contrast echocardiography has an established role for enhancement of the right heart Doppler signals, the detection of intra-cardiac shunts, and most recently for left ventricular cavity opacification (LVO). The use of intravenously administered micro-bubbles to traverse the myocardial microcirculation in order to outline myocardial viability and perfusion has been the source of research studies for a number of years. Despite the enthusiasm of investigators, myocardial contrast echocardiography (MCE) has not attained routine clinical use and LV opacification during stress has been less widely adopted than the data would support. The purpose of this review is to facilitate an understanding of the involved imaging technologies that have made this technique more feasible for clinical practice, and to guide its introduction into the practice of the non-expert user.
Diurnal difference in CAR mRNA expression
Authors: Kanno Yuichiro , Otsuka Satoshi , Hiromasa Takuya , Nakahama Takayuki , Inouye Yoshio
Published: September 2004

Background

The constitutive androstane receptor (CAR, NR1I3) plays a key role in the transcriptional activation of genes that encode xenobiotic/steroid and drug metabolizing enzymes.

Results

The expression of CAR mRNA throughout the circadian rhythm is reported for the first time in phase with the clock gene Bmal1 and in antiphase with the clock-controlled gene Rev-erbα mRNAs, with a peak at Zeitgeber time (ZT) 20 and a trough at ZT8, and a peak/trough ratio of 2.0. The diurnal difference in CAR mRNA expression might underlie the 1.7-fold difference in the magnitude of the PB-dependent induction of CYP2B1/2 mRNA.

Conclusion

The circadian oscillation of xenosensor gene CAR mRNA expression is partially responsible for chronopharmacokinetics and chronopharmacology in disease.
Adaptive evolution of centromere proteins in plants and animals
Authors: Talbert Paul B , Bryson Terri D , Henikoff Steven
Published: September 2004

Background

Centromeres represent the last frontiers of plant and animal genomics. Although they perform a conserved function in chromosome segregation, centromeres are typically composed of repetitive satellite sequences that are rapidly evolving. The nucleosomes of centromeres are characterized by a special H3-like histone (CenH3), which evolves rapidly and adaptively in Drosophila and Arabidopsis. Most plant, animal and fungal centromeres also bind a large protein, centromere protein C (CENP-C), that is characterized by a single 24 amino-acid motif (CENPC motif).

Results

Whereas we find no evidence that mammalian CenH3 (CENP-A) has been evolving adaptively, mammalian CENP-C proteins contain adaptively evolving regions that overlap with regions of DNA-binding activity. In plants we find that CENP-C proteins have complex duplicated regions, with conserved amino and carboxyl termini that are dissimilar in sequence to their counterparts in animals and fungi. Comparisons of Cenpc genes from Arabidopsis species and from grasses revealed multiple regions that are under positive selection, including duplicated exons in some grasses. In contrast to plants and animals, yeast CENP-C (Mif2p) is under negative selection.

Conclusions

CENP-Cs in all plant and animal lineages examined have regions that are rapidly and adaptively evolving. To explain these remarkable evolutionary features for a single-copy gene that is needed at every mitosis, we propose that CENP-Cs, like some CenH3s, suppress meiotic drive of centromeres during female meiosis. This process can account for the rapid evolution and the complexity of centromeric DNA in plants and animals as compared to fungi.
Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis
Authors: Kitamura Kazuya , Nakamoto Yasunari , Kaneko Shuichi , Mukaida Naofumi
Published: September 2004

Breakdown of normal mucosal immunity is one of the major causes for inflammatory bowel disease. Interleukin (IL)-6 is a proinflammatory cytokine produced aberrantly in various types of inflammation, but its role in inflammatory bowel disease is still obscure. Hence, we analyzed the roles of IL-6 in the pathogenesis of murine T cell transfer colitis, whose histopathology resembles Crohn's disease. The transfer of CD4+CD45RBhigh T cells into severe combined immunodeficiency mice induced the infiltration of T cells and macrophages, and the gene expression of CC chemokine receptor (CCR)1, CCR2, CCR5, CXC chemokine receptor 3, their ligands, tumor necrosis factor-α, interferon-γ, and IL-6 was progressively augmented as colitis developed. The incidence of transmural colitis was significantly reduced with a minimal decrease in the severity of colitis in recipients transferred with CD4+CD45RBhigh T cells derived from IL-6-deficient mice compared with those with wild-type mice. Moreover, the gene expression of several cytokines, chemokines, and matrix metalloproteinases was reduced significantly in recipients transferred with IL-6-deficient, mice-derived T cells. These observations suggested that T cell-derived IL-6 may augment the gene expression of several proinflammatory molecules, thereby causing transmural inflammation. Thus, IL-6 might be a promising target for treating transmural inflammation in Crohn's disease, which can lead to severe complications such as strictures, fissures, and fistulas.
Terminal tendon cell differentiation requires the glide/gcm complex
Authors: Soustelle Laurent , Jacques Cécile , Altenhein Benjamin , Technau Gerhard M. , Volk Talila , Giangrande Angela
Published: September 2004

Locomotion relies on stable attachment of muscle fibres to their target sites, a process that allows for muscle contraction to generate movement. Here, we show that glide/gcm and glide2/gcm2, the fly glial cell determinants, are expressed in a subpopulation of embryonic tendon cells and required for their terminal differentiation. By using loss-of-function approaches, we show that in the absence of both genes, muscle attachment to tendon cells is altered, even though the molecular cascade induced by stripe, the tendon cell determinant, is normal. Moreover, we show that glide/gcm activates a new tendon cell gene independently of stripe. Finally, we show that segment polarity genes control the epidermal expression of glide/gcm and determine, within the segment,whether it induces glial or tendon cell-specific markers. Thus, under the control of positional cues, glide/gcm triggers a new molecular pathway involved in terminal tendon cell differentiation, which allows the establishment of functional muscle attachment sites and locomotion.
vhnf1integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish
Authors: Hernandez Rafael E. , Rikhof Holly A. , Bachmann Ruxandra , Moens Cecilia B.
Published: September 2004

The vertebrate hindbrain is transiently divided along the anterior-posterior axis into seven morphologically and molecularly distinct segments, or rhombomeres, that correspond to Hox expression domains. The establishment of a proper `hox code' is required for the development of unique rhombomere identities, including specification of neuronal fates. valentino (val), the zebrafish ortholog of mafB/Kreisler(Kr), encodes a bZip transcription factor that is required cell autonomously for the development of rhombomere (r) 5 and r6 and for activation of Hox group 3 gene expression. Recent work has demonstrated that the expression of val itself depends on three factors: retinoic acid (RA)signals from the paraxial mesoderm; fibroblast growth factor (Fgf) signals from r4; and variant hepatocyte nuclear factor 1 (vhnf1,also known as tcf2), a homeodomain transcription factor expressed posterior to the r4-5 boundary. We have investigated the interactions between these inputs onto val expression in the developing zebrafish hindbrain. We show that RA induces val expression via activation of vhnf1 expression in the hindbrain. Fgf signals from r4, acting through the MapK pathway, then cooperate with Vhnf1 to activate valexpression and subsequent r5 and r6 development. Additionally, vhnf1and val function as part of a multistep process required for the repression of r4 identity in the posterior hindbrain. vhnf1 acts largely independently of val to repress the r4 `hox code'posterior to the r4-5 boundary and therefore to block acquisition of r4-specific neuronal fates in the posterior hindbrain. However, vhnf1is not able to repress all aspects of r4 identity equivalently. valis required downstream of vhnf1 to repress r4-like cell-surface properties, as determined by an `Eph-ephrin code', by repressing ephrin-B2a expression in r5 and r6. The different requirements for vhnf1 and val to repress hoxb1a and ephrin-B2a, respectively, demonstrate that not all aspects of an individual rhombomere's identity are regulated coordinately.
The hedgehog pathway is a modulator of retina regeneration
Authors: Spence Jason R. , Madhavan Mayur , Ewing John D. , Jones David K. , Lehman Bret M. , Del Rio-Tsonis Katia
Published: September 2004

The embryonic chick has the ability to regenerate its retina after it has been completely removed. Here, we provide a detailed characterization of retina regeneration in the embryonic chick at the cellular level. Retina regeneration can occur in two distinct manners. The first is via transdifferentiation, which is induced by members of the Fibroblast growth factor (Fgf) family. The second type of retinal regeneration occurs from the anterior margin of the eye, near the ciliary body (CB) and ciliary marginal zone (CMZ). We show that regeneration from the CB/CMZ is the result of proliferating stem/progenitor cells. This type of regeneration is also stimulated by Fgf2, but we show that it can be activated by Sonic hedgehog(Shh) overexpression when no ectopic Fgf2 is present. Shh-stimulated activation of CB/CMZ regeneration is inhibited by the Fgf receptor (Fgfr)antagonist, PD173074. This indicates that Shh-induced regeneration acts through the Fgf signaling pathway. In addition, we show that the hedgehog (Hh)pathway plays a role in maintenance of the retina pigmented epithelium (RPE),as ectopic Shh expression inhibits transdifferentiation and Hh inhibition increases the transdifferentiation domain. Ectopic Shh expression in the regenerating retina also results in a decrease in the number of ganglion cells present and an increase in apoptosis mostly in the presumptive ganglion cell layer (GCL). However, Hh inhibition increases the number of ganglion cells but does not have an effect on cell death. Taken together, our results suggest that the hedgehog pathway is an important modulator of retina regeneration.
Hypoxia affects mesoderm and enhances hemangioblast specification during early development
Authors: Ramírez-Bergeron Diana L. , Runge Anja , Dahl Karen D. Cowden , Fehling Hans Joerg , Keller Gordon , Simon M. Celeste
Published: September 2004

Hypoxia Inducible Factor (HIF), consisting of HIF1α and ARNT(HIF1β) subunits, activates multiple genes in response to oxygen(O2) deprivation. Arnt–/– mice exhibit substantial defects in blood cell and vessel development. We demonstrate that hypoxia accelerates the expression of Brachyury (a mesoderm-specific transcription factor), BMP4 (a mesoderm-promoting growth factor) and FLK1 (a marker of hemangioblasts, the bipotential progenitor of endothelial and hematopoietic cells) in differentiating ES cell cultures. Significantly, proliferation of embryonic hemangioblasts (BL-CFCs) is regulated by hypoxia, as Arnt+/+ ES cells generate increased numbers of FLK1+ cells, and BL-CFCs with accelerated kinetics in response to low O2. This response is HIF-dependent as Arnt–/– ES cells produce fewer FLK1+ cells and BL-CFCs, under both normoxic and hypoxic conditions. Interestingly, this defect is rescued when Arnt–/– ES cells are co-cultured with Arnt+/+ ES cells. Vegf+/–or Vegf–/– ES cells generate proper numbers of FLK1+ cells but fewer BL-CFCs, suggesting that additional factors regulated by HIF (other than VEGF) are involved in these early events. Thus,hypoxic responses are important for the establishment of various progenitor cells, including early mesoderm and its differentiation into hemangioblasts. Together these data suggest that ineffective responses to hypoxia in Arnt–/– embryos abrogate proper cardiovascular development during early embryogenesis, including the pathways controlling hemangioblast differentiation.
Krüppelis a gap gene in the intermediate germband insectOncopeltus fasciatusand is required for development of both blastoderm and germband-derived segments
Authors: Liu Paul Z. , Kaufman Thomas C.
Published: September 2004

Segmentation in long germband insects such as Drosophila occurs essentially simultaneously across the entire body. A cascade of segmentation genes patterns the embryo along its anterior-posterior axis via subdivision of the blastoderm. This is in contrast to short and intermediate germband modes of segmentation where the anterior segments are formed during the blastoderm stage and the remaining posterior segments arise at later stages from a posterior growth zone. The biphasic character of segment generation in short and intermediate germ insects implies that different formative mechanisms may be operating in blastoderm-derived and germband-derived segments. In Drosophila, the gap gene Krüppel is required for proper formation of the central portion of the embryo. This domain of Krüppel activity in Drosophila corresponds to a region that in short and intermediate germband insects spans both blastoderm and germband-derived segments. We have cloned the Krüppel homolog from the milkweed bug, Oncopeltus fasciatus (Hemiptera, Lygaeidae),an intermediate germband insect. We find that Oncopeltus Krüppelis expressed in a gap-like domain in the thorax during the blastoderm and germband stages of embryogenesis. In order to investigate the function of Krüppel in Oncopeltus segmentation, we generated knockdown phenotypes using RNAi. Loss of Krüppel activity in Oncopeltus results in a large gap phenotype, with loss of the mesothoracic through fourth abdominal segments. Additionally, we find that Krüppel is required to suppress both anterior and posterior Hox gene expression in the central portion of the germband. Our results show that Krüppel is required for both blastoderm-derived and germband-derived segments and indicate that Krüppel function is largely conserved in Oncopeltus and Drosophila despite their divergent embryogenesis.
Specification of adaxial cell fate during maize leaf development
Authors: Juarez Michelle T. , Twigg Richard W. , Timmermans Marja C. P.
Published: September 2004

Dorsoventral (adaxial/abaxial) polarity of the maize leaf is established in the meristem and is maintained throughout organ development to coordinate proper outgrowth and patterning of the leaf. rolled leaf1(rld1) and leafbladeless1 (lbl1) are required for the specification of the adaxial/upper leaf surface. rld1 encodes a class III homeodomain-leucine zipper (HD-ZIPIII) protein whose adaxial expression is spatially defined by miRNA166-directed transcript cleavage on the abaxial side. The semi-dominant Rld1-Original (Rld1-O)mutation, which results from a single nucleotide substitution in the miRNA166 complementary site, leads to persistent expression of mutant transcripts on the abaxial site. This causes the adaxialization or partial reversal of leaf polarity. By contrast, recessive mutations in lbl1 cause the formation of abaxialized leaves. The lbl1 and Rld1-Omutations mutually suppress each other, indicating that these two genes act in the same genetic pathway. Adaxial and meristematic expression of rld1is reduced in lbl1 mutants, indicating that lbl1 acts upstream of rld1 to specify adaxial fate during primordium development. However, rld1 expression in the vasculature of lbl1 is normal, suggesting that the specification of adaxial/abaxial polarity during vascular and primordia development is governed by separate but overlapping pathways. We also show that members of the maize yabbygene family are expressed on the adaxial side of incipient and developing leaf primordia. This expression pattern is unlike that observed in Arabidopsis, where YABBY expression is correlated with abaxial cell fate. The yabby expression patterns in lbl1 and Rld1-O mutants suggest that the yabby genes act downstream in the same pathway as lbl1 and rld1. Moreover, our observations suggest that maize yabby genes may direct lateral organ outgrowth rather than determine cell fate. We propose that a single genetic pathway involving lbl1, rld1 and the yabby genes integrates positional information within the SAM, and leads to adaxial/abaxial patterning and mediolateral outgrowth of the leaf.
Compound leaves: equal to the sum of their parts?
Authors: Champagne Connie , Sinha Neelima
Published: September 2004

The leaves of seed plants can be classified as being either simple or compound according to their shape. Two hypotheses address the homology between simple and compound leaves, which equate either individual leaflets of compound leaves with simple leaves or the entire compound leaf with a simple leaf. Here we discuss the genes that function in simple and compound leaf development, such as KNOX1 genes, including how they interact with growth hormones to link growth regulation and development to cause changes in leaf complexity. Studies of transcription factors that control leaf development, their downstream targets, and how these targets are regulated are areas of inquiry that should increase our understanding of how leaf complexity is regulated and how it evolved through time.
Requirement forSchizosaccharomyces pombeTop3 in the maintenance of chromosome integrity
Authors: Win Thein Z. , Goodwin Adele , Hickson Ian D. , Norbury Chris J. , Wang Shao-Win
Published: September 2004

In Schizosaccharomyces pombe, topoisomerase III is encoded by a single gene, top3+, which is essential for cell viability and proper chromosome segregation. Deletion of rqh1+, which encodes the sole RecQ family helicase in S. pombe, suppresses the lethality caused by loss of top3. Here, we provide evidence suggesting that the lethality in top3 mutants is due to accumulation of aberrant DNA structures that arise during S phase, as judged by pulsed-field gel electrophoresis. Using a top3 shut-off strain, we show here that depletion of Top3 activates the DNA damage checkpoint associated with phosphorylation of the checkpoint kinase Chk1. Despite activation of this checkpoint, top3 cells exit the arrest but fail to undergo faithful chromosome segregation. However, these mitotic defects are secondary to chromosomal abnormalities that lead to the lethality, because advance into mitosis did not adversely affect cell survival. Furthermore, top3 function is required for maintenance of nucleolar structure, possibly due to its ability to prevent recombination at the rDNA loci. Our data are consistent with the notion that Top3 has a key function in homologous recombinational repair during S phase that is essential for ensuring subsequent fidelity of chromosome segregation.
Role for Rab7 in maturation of late autophagic vacuoles
Authors: Jäger Stefanie , Bucci Cecilia , Tanida Isei , Ueno Takashi , Kominami Eiki , Saftig Paul , Eskelinen Eeva-Liisa
Published: September 2004

The small GTP binding protein Rab7 has a role in the late endocytic pathway and lysosome biogenesis. The role of mammalian Rab7 in autophagy is, however, unknown. We have addressed this by inhibiting Rab7 function with RNA interference and overexpression of dominant negative Rab7. We show here that Rab7 was needed for the formation of preferably perinuclear, large aggregates, where the autophagosome marker LC3 colocalised with Rab7 and late endosomal and lysosomal markers. By electron microscopy we showed that these large aggregates corresponded to autophagic vacuoles surrounding late endosomal or lysosomal vesicles. Our experiments with quantitative electron microscopy showed that Rab7 was not needed for the initial maturation of early autophagosomes to late autophagic vacuoles, but that it participated in the final maturation of late autophagic vacuoles. Finally, we showed that the recruitment of Rab7 to autophagic vacuoles was retarded in cells deficient in the lysosomal membrane proteins Lamp1 and Lamp2, which we have recently shown to accumulate late autophagic vacuoles during starvation. In conclusion, our results showed a role for Rab7 in the final maturation of late autophagic vacuoles.
Configuration of Detection Software: A Comparison of Decision and Game Theory Approaches
Authors: Cavusoglu Huseyin , Raghunathan Srinivasan
Published: September 2004

Firms are increasingly relying on software to detect fraud in domains such as security, financial services, tax, and auditing. A fundamental problem in using detection software for fraud detection is achieving the optimal balance between the detection and false-positive rates. Many firms use decision theory to address the configuration problem. Decision theory is based on the presumption that the firm's actions do not influence the behavior of fraudsters. Game theory recognizes the fact that fraudsters do modify their strategies in response to firms' actions. In this paper, we compare decision and game theory approaches to the detection software configuration problem when firms are faced with strategic users. We find that under most circumstances firms incur lower costs when they use the game theory as opposed to the decision theory because the decision theory approach frequently either over- or underconfigures the detection software. However, firms incur the same or lower cost under the decision theory approach compared with the game theory approach in a simultaneous-move game if configurations under decision theory and game theory are sufficiently close. A limitation of the game theory approach is that it requires user-specific utility parameters, which are difficult to estimate. Decision theory, in contrast to game theory, requires the fraud probability estimate, which is more easily obtained.
Sex, Lies, and the Hillblom Estate: A Decision Analysis
Authors: Lippman Steven A. , McCardle Kevin F.
Published: September 2004

We present three approaches to evaluating a publicly detailed, high-stakes, high-risk decision made by an heir-claimant to the estate of Larry Hillblom. The first two approaches are standard: a decision tree focusing on risk aversion and a multiperiod consumption model that highlights the effects of forgone consumption. In the third approach, we embed several Nash bargaining games into the decision tree developed in the first approach.
From the Editors…
Authors: Clemen Robert T. , Kleinmuntz Don N.
Published: September 2004

The first two articles in this issue address the relationship between game theory and decision analysis. How can decision analysts best employ game-theoretic concepts in their prescriptive models? Two additional articles consider the value of prioritization in analyzing a portfolio of research-and-development (R&D) projects and analyze whether it is better to obtain estimates of correlation coefficients from multiple experts or multiple estimates from a single expert.
Convergence of the Least Squares Monte Carlo Approach to American Option Valuation
Authors: Stentoft Lars
Published: September 2004

In a recent paper, Longstaff and Schwartz (2001) suggest a method to American option valuation based on simulation. The method is termed the Least Squares Monte Carlo (LSM) method, and although it has become widely used, not much is known about the properties of the estimator. This paper corrects this shortcoming using theory from the literature on seminonparametric series estimators. A central part of the LSM method is the approximation of a set of conditional expectation functions. We show that the approximations converge to the true expectation functions under general assumptions in a multiperiod, multidimensional setting. We obtain convergence rates in the two-period, multidimensional case, and we discuss the relation between the optimal rate of convergence and the properties of the conditional expectation. Furthermore, we show that the actual price estimates converge to the true price. This provides the mathematical foundation for the use of the LSM method in derivatives research.
Option Pricing Under a Double Exponential Jump Diffusion Model
Authors: Kou S. G. , Wang Hui
Published: September 2004

Analytical tractability is one of the challenges faced by many alternative models that try to generalize the Black-Scholes option pricing model to incorporate more empirical features. The aim of this paper is to extend the analytical tractability of the Black-Scholes model to alternative models with jumps. We demonstrate that a double exponential jump diffusion model can lead to an analytic approximation for finite-horizon American options (by extending the Barone-Adesi and Whaley method) and analytical solutions for popular path-dependent options (such as lookback, barrier, and perpetual American options). Numerical examples indicate that the formulae are easy to implement, and are accurate.
Dividends and Debt with Managerial Agency and Lender Holdup
Authors: Kanatas George , Qi Jianping
Published: September 2004

A well-known view in the literature is that if management is more concerned with the firm's survival than with profitability, it is efficient to use a levered capital structure and thereby transfer the liquidation decision to lenders. Our paper extends this idea to a setting where lenders behave opportunistically when they control the liquidation decision. We show that in this situation, an optimal mix of debt and dividends can mitigate the twin moral hazard problems of the manager and the lender. Given an otherwise optimal capital structure, initiating a dividend policy increases firm value, lowers debt payments, but raises total cash disbursements—interest and dividends—to investors. Numerous other empirical implications of the model are also discussed.
Pricing Path-Dependent Securities by the Extended Tree Method
Authors: Kishimoto Naoki
Published: September 2004

This paper presents a discrete-time method (ET method) for pricing path-dependent securities by the supplementary variable technique and examines the ET method from the point of view of Arrow-Debreu event tree. In particular, this paper identifies sufficient conditions on supplementary variables under which the ET method yields the same price for a path-dependent security as a valuation method based on a comparable Arrow-Debreu event tree. Two examples are provided to illustrate the ET method. The first example is a valuation of collateralized mortgage obligations (CMOs), where the collateral of a CMO is modeled as a pool of mortgage loans with heterogeneous prepayment costs. The second example is a valuation of American average options where the average is computed over a moving period with a fixed length. In addition, this paper presents a measure for the computational size of the ET method and illustrates numerical advantages of the ET method with examples.
Primal-Dual Simulation Algorithm for Pricing Multidimensional American Options
Authors: Andersen Leif , Broadie Mark
Published: September 2004

This paper describes a practical algorithm based on Monte Carlo simulation for the pricing of multidimensional American (i.e., continuously exercisable) and Bermudan (i.e., discretely exercisable) options. The method generates both lower and upper bounds for the Bermudan option price and hence gives valid confidence intervals for the true value. Lower bounds can be generated using any number of primal algorithms. Upper bounds are generated using a new Monte Carlo algorithm based on the duality representation of the Bermudan value function suggested independently in Haugh and Kogan (2004) and Rogers (2002). Our proposed algorithm can handle virtually any type of process dynamics, factor structure, and payout specification. Computational results for a variety of multifactor equity and interest-rate options demonstrate the simplicity and efficiency of the proposed algorithm. In particular, we use the proposed method to examine and verify the tightness of frequently used exercise rules in Bermudan swaption markets.
Micafungin
Authors: Carver Peggy L
Published: September 2004

OBJECTIVE

To review the pharmacology, mycology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of micafungin, an echinocandin antifungal agent.

DATA SOURCES

A MEDLINE search, restricted to English language, was conducted from 1978 to November 2003. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2003 and information available through the manufacturer's Web site.

STUDY SELECTION AND DATA EXTRACTION

In vitro and preclinical studies, as well as Phase II and III clinical trials, were evaluated to summarize the clinical efficacy and safety of micafungin. All published and unpublished trials and abstracts citing micafungin were selected.

DATA SYNTHESIS

Micafungin has shown in vitro activity against many yeasts and a variety of molds. Micafungin can be administered only parenterally. Efficacy has been illustrated in open noncomparative studies of esophageal candidiasis in HIV-infected patients and in comparative trials as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Adverse events appear mild and limited; the most commonly reported adverse events include hyperbilirubinemia, nausea, and diarrhea.

CONCLUSIONS

Micafungin has activity against Aspergillus spp. and a variety of Candida spp., including azole-resistant strains. Micafungin demonstrates efficacy in the treatment of esophageal candidiasis in HIV-infected patients and appears superior to fluconazole as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Based on case reports and in vitro efficacy, micafungin may prove to be a clinically useful agent in the treatment of other fungal diseases; however, these indications await the results of clinical trials.
Impact of Fluconazole Administration on Outcomes in Critically Ill Patients
Authors: Garrelts James C , Schroeder Todd R , Harrison Paul B
Published: September 2004

BACKGROUND

Serious infections caused by Candida spp. are an increasingly important cause of morbidity and mortality in critically ill patients. It is unclear which patients will benefit from therapy and at what point to institute treatment.

OBJECTIVE

To evaluate the impact of administration of fluconazole therapy in critically ill trauma patients on mortality, length of hospital stay, incidence of deep-seated fungal infection, and positive fungal cultures from any site.

METHODS

We conducted a retrospective, matched case—control study of 116 critically ill surgical trauma patients who did or did not receive fluconazole. Patients were followed until hospital discharge or death. A consecutive sample of 58 patients who received fluconazole was selected. A parallel group of patients was evaluated, from which 58 were matched with fluconazole-treated patients based on age (± 5 y), gender, and APACHE II score (± 3).

RESULTS

The groups of patients were well matched, with the exception of central venous catheter placement and broad-spectrum antibiotic use. We found no difference between groups in hospital mortality (21% vs 26%; p = 0.661) or incidence of deep-seated fungal infection (0% vs 2%; p = NS). However, patients receiving fluconazole had a significantly longer stay in both the intensive care unit (ICU) (18 ± 13 vs 7 ± 11 days; p < 0.001) and hospital (25 ± 15 vs 9 ± 11 days; p < 0.001). Fluconazole patients were significantly more likely to have Candida cultured from sites associated with colonization (43% vs 2%; p < 0.001), possibly explaining why they received fluconazole.

CONCLUSIONS

We were unable to detect a benefit from use of fluconazole in our surgical trauma patient population. Isolation of Candida from the mouth or throat alone, in the absence of correlating clinical signs of infection, should not lead to initiation of fluconazole therapy. Fluconazole use should be reserved for carefully selected patients in the trauma ICU setting.
Urinary Tract Infections During Pregnancy
Authors: Le Jennifer , Briggs Gerald G , McKeown Anna , Bustillo Gerardo
Published: September 2004

OBJECTIVE

To provide a comprehensive review of urinary tract infections (UTIs) during pregnancy. All aspects of UTIs, including epidemiology, pathogenesis, resistance, clinical features, diagnosis, treatment, and prevention, were reviewed.

DATA SOURCES

MEDLINE (1966–August 2003) and Cochrane Library searches were performed using the key search terms urinary tract infection, pyelonephritis, cystitis, asymptomatic bacteriuria, and resistance.

STUDY SELECTION AND DATA EXTRACTION

All article abstracts were evaluated for relevance. Only articles pertaining to pregnancy were included. The majority of published literature were review articles; the number of original clinical studies was limited.

DATA SYNTHESIS

UTIs are the most common bacterial infections during pregnancy. They are characterized by the presence of significant bacteria anywhere along the urinary tract. Pyelonephritis is the most common severe bacterial infection that can lead to perinatal and maternal complications including premature delivery, infants with low birth weight, fetal mortality, preeclampsia, pregnancy-induced hypertension, anemia, thrombocytopenia, and transient renal insufficiency. Enterobacteriaceae account for 90% of UTIs. The common antibiotics used are nitrofurantoin, cefazolin, cephalexin, ceftriaxone, and gentamicin.

CONCLUSIONS

Therapeutic management of UTIs in pregnancy requires proper diagnostic workup and thorough understanding of antimicrobial agents to optimize maternal outcome, ensure safety to the fetus, and prevent complications that lead to significant morbidity and mortality in both the fetus and the mother.