bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) on fatty acid availability and neural tube formation in cynomolgus macaque, Macaca fascicularis
Authors: Moran F. M. , Hendrickx A. G. , Shideler S. , Overstreet J. W. , Watkins S. M. , Lasley B. L. 
Published: February 2004

Abstract2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is known to alter carbohydrate utilization and specific steps in lipid metabolism. TCDD interacts with estradiol in mobilizing specific fatty acids in chickens that may be a cause of cranial/beak malformations in this species. This study was designed to test the hypothesis that TCDD simultaneously alters critical fatty acid mobilization during early pregnancy and determine if those changes correlate to morphological defects of the developing neural tube in the nonhuman primate. Cynomolgus macaques were treated with a single dose of 4 μg/kg body weight (BW) TCDD on gestational day 15 or 20. Pregnancies were terminated by hysterectomy on gestational day 24–26 and embryos were examined to determine morphology of the developing neural tube. Maternal blood samples were used for fatty acid quantification. Embryos exhibited cellular changes, mainly increased cell death, and intercellular spaces in the neural tube, suggestive of an adverse effect on the developing nervous system. Significant decreases on fatty acid composition were found on some of the eight classes of lipids analyzed. Particularly, a decrease was observed in the n‐3 (40–60%) and n‐6 (47–75%) essential fatty acids in treated pregnancies compared to untreated controls. These data demonstrate the effect of TCDD in decreasing maternal levels of n‐3 and n‐6 fatty acids that are considered necessary for normal development in mammals. Since neural tube development is dependent, in part, on n‐3 and n‐6 fatty acids, it is possible that the limitation of these essential fatty acids in plasma resulted in the observed detrimental effects on early brain development. Birth Defects Res B 71:37–46, 2004. © 2004 Wiley‐Liss, Inc.
Amidic modification of valproic acid reduces skeletal teratogenicity in mice
Authors: Okada Akinobu , Kurihara Hiroshi , Aoki Yoshinobu , Bialer Meir , Fujiwara Michio 
Published: February 2004

AbstractBACKGROUND: The antiepileptic drug valproic acid (VPA) is well known to cause neural tube and skeletal defects in both humans and animals. The amidic VPA analogues valpromide (VPD) and valnoctamide (VCD) have much lower teratogenicity than VPA inducing exencephaly in mice. The objective of this study was to investigate the teratogenic effects of VPA, VPD, and VCD on the skeleton of NMRI mice. METHODS: Pregnant NMRI mice were given a single subcutaneous injection of VPA (400 and 800 mg/kg), VPD (800 mg/kg), or VCD (800 mg/kg) on the morning of gestation day (GD) 8. Cesarean section was carried out on GD 18. Live fetuses were double‐stained for bone and cartilage and their skeletons were examined. RESULTS: Significant increases in fetal loss and exencephaly rate were observed with VPA at 800 mg/kg compared to the vehicle control. There were no significant differences between either VPD or VCD and the control groups for any parameter at cesarean section. A number of abnormalities were dose‐dependently induced at high incidences by VPA in both the cartilage and bone of vertebrae, ribs and sternum. In contrast, lower frequencies of abnormality were exhibited with VPD and VCD than VPA in all skeletons affected by VPA. CONCLUSIONS: These findings clearly indicate that VPD and VCD are distinctly less teratogenic than VPA in the induction of not only neural tube defects, but also skeletal abnormalities. A structure‐teratogenicity relationship of VPA on the skeleton is suspected. Birth Defects Res B 71:47–53, 2004. © 2004 Wiley‐Liss, Inc.
Effects of restraint stress in gestation: Implications for rodent developmental toxicology studies
Authors: Golub Mari S. , Campbell Marlissa A. , Kaufman Farla L. , Iyer Poorni , Li Ling‐Hong , Donald James M. , Morgan James E. 
Published: February 2004

AbstractRestraint has been used as a procedure to study the effects of stress on gestation outcome in rodents. The effects of restraint could potentially be used as a model for the impact of general stress produced by high doses of toxicants and other interventions. In mice, restraint in the peri‐implantation period leads to implantation failure, and restraint at appropriate times in organogenesis produces cleft palate, supernumerary ribs, and resorption. In rats, there is some evidence for an association with restraint for implantation failure, but not for the morphological anomalies. Restraint in late gestation alters adult sexual behavior of male rat offspring, but consequences for their fertility are not known. Intrauterine growth retardation is not commonly associated with gestational restraint. In the few studies where they have been directly compared, different restraint procedures produced graded, qualitatively different, or no effects. Adrenocortical hormones have been implicated as mediating the effect of restraint on cleft palate, but not on supernumerary ribs, implantation failure, or sexual differentiation. Given the variety of restraint procedures and the varying species‐dependent consequences, it is not possible to infer a generalizable pattern of developmental effects due to gestational stress from the restraint literature. As an alternative approach, contemporary methods in gene expression and developmental biology could profitably be applied to understanding different patterns of stress‐mediated effects of toxicant exposures on intrauterine development. Birth Defects Res B 71:26–36, 2004. © 2004 Wiley‐Liss, Inc.
Why does the species problem still persist?
Authors: Reydon Thomas A.C. 
Published: February 2004

AbstractDespite many years of discussion, the species problem has still not been adequately resolved. Why is this the case? Here I discuss two recent suggested answers to this question that place the blame on the species problem's empirical aspects or on its philosophical aspects. In contrast, I argue that neither of these two faces of the species problem constitute the principal cause of the species problem's persistence. Rather, they are merely symptoms of the real cause: the species problem has not yet gone away because of a failure to recognize that not one but a number of distinct concepts are at the heart of the problem. To illustrate this point, a recently proposed solution to the problem is examined: the suggestion to understand the concept of species as a family resemblance concept. BioEssays 26:300–305, 2004. © 2004 Wiley Periodicals, Inc.
The polychaete Platynereis dumerilii (Annelida): a laboratory animal with spiralian cleavage, lifelong segment proliferation and a mixed benthic/pelagic life cycle
Authors: Fischer Albrecht , Dorresteijn Adriaan 
Published: February 2004

AbstractPlatynereis dumerilii, a marine polychaetous annelid with indirect development, can be continuously bred in the laboratory. Here, we describe its spectacular reproduction and development and address a number of open research problems. Oogenesis is easily studied because the oocytes grow while floating in the coelom. Unlike the embryos of other model spiralians, the Platynereis embryo is transparent giving insight into the dynamic structures and processes inside the cells that accompany the prevailing anisotropic cleavages. Functional studies on cell specification and differential gene expression in embryos, larvae, and later stages are underway. Lifelong proliferation of uniform trunk segments qualifies Platynereis as a model for the study of gene expression and of the functional circuitry of this process. Platynereis can also become a stepping stone in the comparison of segmentation between annelids and arthropods because it comes closer to the putative ancestral morphology and style of development than other model annelids. BioEssays 26:314–325, 2004. © 2004 Wiley Periodicals, Inc.
Werner syndrome protein, the MRE11 complex and ATR: menage‐à‐trois in guarding genome stability during DNA replication?
Authors: Pichierri Pietro , Franchitto Annapaola 
Published: February 2004

AbstractThe correct execution of the DNA replication process is crucially import for the maintenance of genome integrity of the cell. Several types of sources, both endogenous and exogenous, can give rise to DNA damage leading to the DNA replication fork arrest. The processes by which replication blockage is sensed by checkpoint sensors and how the pathway leading to resolution of stalled forks is activated are still not completely understood. However, recent emerging evidence suggests that one candidate for a sensor of replication stress is ATR and that, together with a member of RecQ family helicases, Werner syndrome protein (WRN) and MRE11 complex, can collaborate to promote the restarting of DNA synthesis through the resolution of stalled replication forks. Here, we discuss how WRN, the MRE11 complex and the ATR kinase could work together in response to replication blockage to avoid DNA replication fork collapse and genome instability. BioEssays 26:306–313, 2004. © 2004 Wiley Periodicals, Inc.
Problems of somatic mutation and cancer
Authors: Frank Steven A. , Nowak Martin A. 
Published: February 2004

AbstractSomatic mutation plays a key role in transforming normal cells into cancerous cells. The analysis of cancer progression therefore requires the study of how point mutations and chromosomal mutations accumulate in cellular lineages. The spread of somatic mutations depends on the mutation rate, the number of cell divisions in the history of a cellular lineage, and the nature of competition between different cellular lineages. We consider how various aspects of tissue architecture and cellular competition affect the pace of mutation accumulation. We also discuss the rise and fall of somatic mutation rates during cancer progression. BioEssays 26:291–299, 2004. © 2004 Wiley Periodicals, Inc.
Hypoxia‐inducible factor‐1 and oncogenic signalling
Authors: Bárdos Julia I. , Ashcroft Margaret 
Published: February 2004

AbstractAn understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival and proliferation, resulting in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc.
Is sperm capacitation analogous to early phases of Ca2+‐triggered membrane fusion in somatic cells and viruses?
Authors: Tulsiani Daulat R.P. , Abou‐Haila Aïda 
Published: February 2004

AbstractAn important feature of male fertility is the physiological priming of spermatozoa by a multifaceted process collectively referred to as capacitation. The end point of this evasive process is the hyperactivated spermatozoa capable of binding to terminal sugar residues on the egg's extracellular coat, the zona pellucida (ZP), and undergoing acrosomal exocytosis (i.e., induction of the acrosome reaction). The hydrolytic action of acrosomal enzymes released at the site of zona binding, along with the enhanced thrust generated by the hyperactivated beat pattern of the bound spermatozoa, are important factors that regulate the penetration of ZP and fertilization of the egg. Despite many advances in identifying sperm components that promote capacitation, the mechanism underlying the calcium‐triggered process remains elusive. The purpose of this review article is to focus on new advances that have enhanced our understanding of in vivo/in vitro capacitation, a prerequisite event resulting from a dramatic modification and reorganization of the sperm membrane molecules. Special emphasis has been laid on accumulating evidence suggesting potential similarities between the sperm capacitation and early phases of calcium‐triggered membrane fusion (i.e., tethering and docking) during secretory and endocytotic pathways among eukaryotes. BioEssays 26:281–290, 2004. © 2004 Wiley Periodicals, Inc.
Carbon monoxide in biology and medicine
Authors: Ryter Stefan W. , Otterbein Leo E. 
Published: February 2004

AbstractCarbon monoxide (CO), a product of organic oxidation processes, arises in vivo during cellular metabolism, most notably heme degradation. CO binds to the heme iron of most hemoproteins. Tissue hypoxia following hemoglobin saturation represents a principle cause of CO‐induced mortality in higher organisms, though cellular targets cannot be excluded. Despite extreme toxicity at high concentrations, low concentrations of CO can confer cytoprotection during ischemia/reperfusion or inflammation‐induced tissue injury. Likewise, heme oxygenase, an enzyme that produces CO, biliverdin and iron, as well as a secondary increase in ferritin synthesis, from the oxidation of heme, can confer protection in vivo and in vitro. CO has been shown to affect several intracellular signaling pathways, including guanylate cyclase, which generates guanosine 3′:5′ cyclic monophosphate and the mitogen‐activated protein kinases (MAPK). Such pathways mediate, in part, the known vasoregulatory, anti‐inflammatory, anti‐apoptotic and anti‐proliferative effects of this gas. Exogenous CO delivered at low concentrations is showing therapeutic potential as an anti‐inflammatory agent and as such can modulate numerous pathophysiological states. This review will delve into the biological significance and medical applications of this gas molecule. BioEssays 26:270–280, 2004. © 2004 Wiley Periodicals, Inc.
Making more heart muscle
Authors: van den Hoff Maurice JB , Kruithof Boudewijn PT , Moorman Antoon FM 
Published: February 2004

AbstractPostnatally, heart muscle cells almost completely lose their ability to divide, which makes their loss after trauma irreversible. Potential repair by cell grafting or mobilizing endogenous cells is of particular interest for possible treatments for heart disease, where the poor capacity for cardiomyocyte proliferation probably contributes to the irreversibility of heart failure. Knowledge of the molecular mechanisms that underly formation of heart muscle cells might provide opportunities to repair the diseased heart by induction of (trans) differentiation of endogenous or exogenous cells into heart muscle cells. We briefly review the molecular mechanisms involved in early development of the linear heart tube by differentiation of mesodermal cells into heart muscle cells. Because the initial heart tube does not comprise all the cardiac compartments present in the adult heart, heart muscle cells are added to the distal borders of the tube and within the tube. At both distal borders, mesodermal cell are recruited into the cardiac lineage and, within the heart tube, muscular septa are formed. In this review, the relative late additions of heart muscle cells to the linear heart tube are described and the potential underlying molecular mechanisms are discussed. BioEssays 26:248–261, 2004. Wiley Periodicals, Inc.
Rac1 and Rac2 GTPases in haematopoiesis
Authors: Weston Victoria J. , Stankovic Tatjana 
Published: February 2004

AbstractThe highly homologous Rac1 and Rac2 GTPases are co‐expressed in cells of haematopoietic origin and are likely to show some functional redundancy. While disruption of the Rac2 gene in mice has provided insight into some of its functions, Rac1 null mice are embryonic lethal and only recently has conditional gene disruption been possible. Consequently, two articles1,2 have recently elucidated some overlapping and unique key roles of Rac1 and Rac2 in haematopoietic processes including specialized roles in innate and humoral immunity. BioEssays 26:221–224, 2004. © 2004 Wiley Periodicals, Inc.
Dynamic regulation of DNA methylation coupled transcriptional repression: BDNF regulation by MeCP2
Authors: Wade Paul A. 
Published: February 2004

AbstractA recurrent theme in eukaryotic genome regulation stipulates that the properties of DNA are strongly influenced by the nucleoprotein complex into which it is assembled. Methylation of cytosine residues in vertebrate genomes has been implicated in influencing the assembly of locally repressive chromatin architecture. Current models suggest that covalent modification of DNA results in heritable, long‐term transcriptional silencing. In October of 2003, two manuscripts1,2 were published that challenge important aspects of this model, suggesting that modulation of both DNA methylation itself, as well as the machinery implicated in its interpretation, are involved in acute gene regulation. BioEssays 26:217–220, 2004. © 2004 Wiley Periodicals, Inc.
A Global View on Parametric and Nonparametric Approaches to the Analysis of Ordered Categorical Data
Authors: Munzel Ullrich , Langer Frank 
Published: February 2004

AbstractRank approaches are very common in the analysis of ordered categorical data but can only be interpreted on an experiment‐wise level. Therefore, parametric tests from linear models, although based on metric structures, are used frequently to analyze this type of data. So the questions arise 1. what parametric tests measure in this context and 2. whether the rank approach could be modified to achieve a global level of interpretation. A possible solution to question 2. offers the so called ridit approach, which is based on known reference distributions. In this paper we discuss a global view that shows how rank analysis and ridit analyses are related and how parametric procedures fit into the same framework. The use of the uniform distribution as a reference in the ridit approach gives an explanation to question 1. The asymptotic multivariate normality of the effect estimators is shown and robust test statistics are discussed. Type I and type II error rates are examined in simulation studies and the approach is applied to a toxicological example. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Exact Tests for Comparing Two Paired Proportions with Incomplete Data
Authors: Tang Man‐Lai , Tang Nian‐Sheng 
Published: February 2004

AbstractVarious asymptotic test procedures have been developed previously for testing the equality of two binomial proportions with partially incomplete paired data. Test procedures that discard incomplete observations have been shown to be less powerful than those procedures that utilize all available observations. On the other hand, asymptotic test procedures that utilize all available observations may not be reliable in small‐sample problems or sparse data structures. In this article, unconditional exact test procedures are proposed for testing the equality of two paired binomial proportions with partially incomplete paired data under a random mechanism. The proposed unconditional exact test methods are illustrated with real data from a neurological study. Empirical studies are conducted to investigate the performance of these and other test procedures with respect to size and power. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A New Quantitative Method for Analysing Unreplicated Factorial Designs
Authors: Chen Ying , Kunert Joachim 
Published: February 2004

AbstractThe paper proposes a new method for the analysis of unreplicated factorial designs. The new method does not use an estimate of the error variance and has the potential to identify up to m – 1 active contrasts, where m is the number of contrasts in the study. It can be shown that the proposed test statistic, called MaxUr, is a function of the generalized likelihood ratio test statistic under normality, which was also used by Al‐Shiha and Yang (1999). Our strategy to identify active contrasts using MaxUr, however, is different from the multistage procedure proposed by Al‐Shiha and Yang (1999). Additionally, our simulation study seems to show that the new method is superior to Al‐Shiha and Yang's (1999) method.In order to test the performance of the new method, we did an extensive simulation study based on 10,000 samples to compare the new method with 12 other methods from the literature. To reasonably compare these methods, some of the 12 existing methods had to be slightly modified, such that the probability of falsely rejecting the global null hypothesis of no active factors was 0.05 for all methods. Two types of evaluation standard were used, the empirical power and the loss of decision. The results show that the new method performs very well, especially for large number of active contrasts (say more than 3 out of 15).A second purpose of the simulation study was to compare the performance of two well‐known estimates for the variance. One is the PSE introduced by Lenth (1989), the other the ASE introduced by Dong (1993). The simulation study confirmed the approximations of Kunert (1997) which indicate that Dong's (1993) estimate should perform better for small numbers of active factors. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sample Size Calculation for Clinical Studies on the Efficacy of a New Contraceptive Method
Authors: Benda Norbert , Gerlinger Christoph , van der Meulen Egbert A. , Endrikat Jan 
Published: February 2004

AbstractThe current guideline of the European Agency for the Evaluation of Medicinal Products (EMEA) on the clinical investigation of steroid contraceptives in women, which was prepared by the Committee for Proprietary Medicinal Products (CPMP), calls for the calculation of a confidence interval for the Pearl Index, a widely used measure to describe the reliability of a contraceptive method. The key studies should be large enough to give a Pearl Index with a 95% confidence interval such that the difference between the upper limit of the confidence interval and the corresponding point estimate does not exceed a given margin. As a consequence of this guidance, the success probability of a Pearl Index study is given by its capability, i.e. probability to fulfil this criterion. The resulting power function based on the necessary exposure time does not increase strictly. The minimum exposure time Tmin should be calculated such that this function exceeds a given probability for all T ≥ Tmin.In this paper, the underlying model is discussed, and definitions and formulae are given for the assumption of a Poisson model. The necessary total exposure time is calculated as a function of a given true pregnancy rate.In addition, some simulations were conducted for the model where a drop‐out mechanism is incorporated into the process. Assuming an exponential distribution for the time to drop‐out the phenomenon that the power does not increase strictly with exposure time is less pronounced. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)