bluuebunny/crossref_metadata_2025 huggingface dataset:
Chorionic villus sampling: A distinctive teratogenic effect on fingers?
Authors: Golden Caroline M. , Ryan Louise M. , Holmes Lewis B.
Published: August 2003

BACKGROUND

An increased frequency of major limb malformations, especially terminal transverse limb defects, have been described in several studies of birth defects in children who had been exposed to the prenatal diagnosis procedure known as chorionic villus sampling (CVS). Vascular disruption has been proposed as the mechanism behind the fetal effect. We postulate that this mechanism is more likely to affect one or two middle fingers, rather than all five fingers. A recent report of the frequency of defects in any or all fingers in an unexposed control population enabled us to assess whether CVS is associated with an increased frequency of defects involving one or two fingers, as well as terminal transverse limb defects.

METHODS

The frequency of limb‐reduction defects affecting one or more fingers or toes, including those with constriction rings and tissue loss, in published studies of 20,236 children who had been exposed to CVS was compared with the frequency in 161,252 newborn infants who had not been exposed to CVS. Children with recognized genetic disorders were excluded.

RESULTS

Several aspects of the limb deficiencies were more common in the CVS‐exposed infants than in unexposed controls. The former were more likely to have: 1) any type of limb deficiency involving one or more fingers (p< .001); 2) absence/hypoplasia of two fingers (p< .001); and 3) absence/hypoplasia of all five fingers (p= .015). The absence of the distal portion of the third finger was a distinctive type of limb‐reduction defect in CVS‐exposed infants.

CONCLUSIONS

The occurrence of deficiencies in one or two fingers, including those designated as “amniotic band deformities,” are as common as terminal transverse limb defects in CVS‐exposed infants, and both are much more common than in unexposed infants. The absence of the distal portion of the third finger, with tapering and stiff joints, appears to be a distinctive effect of exposure to CVS. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Association of congenital diaphragmatic hernia with limb‐reduction defects
Authors: van Dooren Marieke F. , Brooks Alice S. , Tibboel Dick , Torfs Claudine P.
Published: August 2003

BACKGROUND

The pathogenesis of congenital diaphragmatic hernia (CDH), a severe birth defect, is not well understood; however, both developmental genes and environmental factors have been suggested to be involved. CDH is frequently associated with malformations of other structures, such as limbs, whose embryogenesis is better understood. An examination of the co‐occurrence of developmental defects may provide clues as to the origin and timing of the insult to the diaphragm and limbs. Our focus was on CDH‐associated limb‐reduction defects (LRDs).

METHODS

For this descriptive study, we reviewed the medical records of infants with a posterolateral (Bochdalek) CDH and an associated LRD among 146 patients from the Sophia Children's Hospital, and among 810 infants and 36 stillbirths from the California Birth Defects Monitoring Program (CBDMP).

RESULTS

In the hospital group, 14 patients (10%) had an associated limb defect, of which about one‐third were LRDs (of these, most were of a nonsevere type, such as hypoplasia of fingers). In the registry group, a limb defect was found in 162 cases (18.5%), 18 of which were mostly severe LRD (usually of the upper extremities). Additional congenital anomalies were observed in all CDH‐LRD cases in both groups.

CONCLUSIONS

In the registry group, 77.8% of LRDs were either bilateral or ipsilateral, and were mostly preaxial, suggesting an early embryological insult affecting both precursor anlages. These results, from large numbers of cases, support the notion of a developmental association between CDH and LRD, as has been observed in several knockout mice. Future analyses of candidate genes from patients with CDH and LRD may elucidate this developmental association in humans. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Malformations of the cranium, vertebral column, and related central nervous system: Morphologic heterogeneity may indicate biological diversity
Authors: Davies Belinda R. , Durán Marco
Published: August 2003

BACKGROUND:

We conducted an autopsy study of neural tube defects (NTDs) to determine whether there is a relation between the localization of the lesion and the sex of the fetus or infant, and the presence of other malformations.

METHODS:

Included were 97 autopsies of infants/fetuses with anencephaly or spina bifida at any level and weighing more than 500 gm. The topographical divisions studied were: 1) isolated cranial lesions, 2) superior spina bifida with or without occipital lesion, and 3) isolated lower spina bifida.

RESULTS:

In group 1 (46 cases) there were lesions of the vertebral column, mainly cervical, and other anomalies of the “schisis” type. Group 2 (24 cases) showed more extensive involvement of the vertebral column and more cases with multiple anomalies (p = 0.001) of a varied spectrum, not only the schisis type; in group 3 (27 cases) the cases involved a few other malformations. In group 2 there was no sex preference (females 46%), but the other, more localized lesions (groups 1 and 3) were found predominantly in females (71%).

CONCLUSIONS:

Localized lesions, whether involving the cranium or lumbar spine, are formed by a mechanism that favors the female gender, whereas upper spina bifida, which is usually accompanied by cranial involvement, results from another mechanism (possibly vascular disruption) and is frequently accompanied by other malformations. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Angiotensin II‐receptor‐antagonists: Further evidence of fetotoxicity but not teratogenicity
Authors: Schaefer Christof
Published: August 2003

BACKGROUND

Like angiotensin converting enzyme (ACE) inhibitors angiotensin II (AT II)‐receptor‐antagonists may cause persistent or even lethal fetotoxic defects when used during the late second or third trimester. There are insufficient data on first‐trimester exposure to these substances in terms of teratogenicity. The two databases of the Berlin Teratology Information Service (TIS) were evaluated for pregnancy outcome following exposure to AT II‐receptor‐antagonists. One database covers case reports on newborns with congenital abnormalities identified after birth, in which drug‐effect associations can be evaluated retrospectively. The other enrolls women prospectively according to exposure to particular drugs during pregnancy, with follow‐up of pregnancy outcome.

CASES

Five cases (four retrospective and one prospective) involving late‐pregnancy use of AT II‐receptor‐antagonists were recently reported to us, each of which included one or more of the following abnormalities: oligohydramnios/anhydramnios, anuria, hypoplastic skull bones, limb contractions, lung hypoplasia, and neonatal death. Among 37 prospectively enrolled first‐trimester‐exposed pregnancies there were 30 live births including one with a major malformation (cleft palate). One pregnancy was electively terminated after exencephaly had been diagnosed.

CONCLUSIONS

AT II‐receptor‐antagonists may induce fetotoxic effects when used in the second and third trimesters. The available data on first‐trimester use do not strongly support a teratogenic potential. AT II‐receptor‐antagonists should not be used by pregnant women. In case of inadvertent exposure, therapy should be changed to the known antihypertensives of choice (e.g., metoprolol, methyldopa, and hydralazine) and fetotoxic effects should be ruled out by ultrasound. Treatment with AT II‐receptor‐antagonists during early pregnancy is not in itself an indication for termination of a wanted pregnancy. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Joint laxity and the risk of clubfoot
Authors: Olshan Andrew F. , Schroeder Jane C. , Alderman Beth W. , Mosca Vincent S.
Published: August 2003

BACKGROUND

Clubfoot is a relatively common and potentially disabling birth defect. The etiology of clubfoot (talipes equinovarus [TEV]) is not known. Joint laxity, or hypermobility, is a suspected risk factor for congenital hip dislocation and clubfoot.

METHODS

We conducted a case‐control study of TEV in five western Washington counties. A total of 239 cases of TEV were identified from hospital and outpatient sources from 1986 to 1994. Controls (n = 356) were identified by random‐digit dialing (RDD). Parents were interviewed over the telephone, and medical records were abstracted. In‐person measurements of four joint laxity indices in parents and the index child were obtained.

RESULTS

Moderately elevated adjusted odds ratios (ORs) were found for extension >90° of the entire little finger, and extension of all four fingers to a position parallel to the forearm (OR = 1.6; 95% CI = 0.9–2.9; and OR = 1.7; CI = 1.1–2.5; respectively). No elevation in the OR was found for the wrist and elbow laxity measures. No consistent pattern of association between joint laxity measures in parents and an elevated OR of clubfoot among their children was found.

CONCLUSIONS

The results of this study suggest a role for joint laxity in the etiology of TEV. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
Expression of Hoxb‐5 during human lung development and in congenital lung malformations
Authors: Volpe MaryAnn V. , Pham Lucia , Lessin Marc , Ralston Steven J. , Bhan Ina , Cutz Ernest , Nielsen Heber C.
Published: August 2003

BACKGROUND:

We have previously shown that the Hox gene Hoxb‐5 is necessary for normal mouse lung branching morphogenesis. Abnormal Hoxb‐5 regulation causes specific alterations in airway branching. We hypothesized that Hoxb‐5 is similarly involved in human lung branching morphogenesis, and is abnormally expressed in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), both of which are congenital lung malformations with abnormal airway development.

METHODS:

The temporal, spatial, and cellular expression of the Hoxb‐5 protein was evaluated in normal human lung and BPS and CCAM tissue using Western blot analysis and immunocytochemistry.

RESULTS:

The expression of Hoxb‐5 during human lung development showed strong similarities to that during mouse lung development. Western blots showed high Hoxb‐5 protein levels in the pseudoglandular period (PSG), decreased but sustained levels in the canalicular period (CAN), and negligible levels during the alveolar period (ALV). Immunocytochemistry showed Hoxb‐5 protein expression in mesenchymal cells around branching airways in the pseuodglandular period, subepithelial fibroblast localization (especially at airway branch points) in the CAN and minimal expression in the ALV. In BPS and CCAM tissue, Hoxb‐5 protein levels were increased compared to age‐ and developmentally‐matched lung tissue, and were more similar to the PSG and CAN with Hoxb‐5–positive cells in mesenchyme surrounding abnormally branched airways.

CONCLUSIONS:

Hoxb‐5 expression during human lung branching morphogenesis, which is similar to that observed in mouse lung development, indicates that it plays a role in controlling airway patterning. This notion is supported by results from BPS and CCAM tissue, in which Hoxb‐5 is maintained in a manner typical of an earlier developmental stage and is associated with development of abnormal lung tissue. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.
The effect of exposure to high flux density static and pulsed magnetic fields on lymphocyte function
Authors: Aldinucci Carlo , Garcia Julian Blanco , Palmi Mitri , Sgaragli Gianpietro , Benocci Alberto , Meini Antonella , Pessina Federica , Rossi Claudio , Bonechi Claudia , Pessina Gian Paolo
Published: August 2003

We investigated whether a combination of static electromagnetic field (EMF) at a flux density of 4.75 T together with pulsed EMF at a flux density of 0.7 mT generated by an NMR apparatus (NMRF), could promote movements of Ca2+, cell proliferation, and the eventual production of proinflammatory cytokines in human lymphocytes as well as in Jurkat cells, after exposure to the field for 1 h. The same study was also performed after activation of cells with 5 μg/ml phytohaemagglutinin (PHA) immediately before the exposure period. Our results clearly demonstrate that NMRF exposure increases the [Ca2+]i, without any proliferative, or activating, or proinflammatory effect on both normal and PHA stimulated lymphocytes. Accordingly, the levels of interferon γ, tumor necrosis factor α, interleukin‐1β, interleukin‐2, and interleukin‐6 remained unvaried after exposure. Exposure of Jurkat cells statistically decreased the [Ca2+]i and the proliferation. This is consistent with the low levels of IL‐2 measured in supernatants of these cells after exposure. On the whole our data suggest that static and pulsed NMRF exposure contribute synergistically in the increase of the [Ca2+]i without any activating or proinflammatory effect either in normal or in PHA challenged lymphocytes. In Jurkat cells, by changing the properties of cell membranes, NMRF exposure can influence Ca2+ transport processes and hence Ca2+ homeostasis, causing a marked decrease of proliferation. Bioelectromagnetics 24:373–379, 2003. © 2003 Wiley‐Liss, Inc.
Skin temperature changes induced by strong static magnetic field exposure
Authors: Ichioka Shigeru , Minegishi Masayuki , Iwasaka Masakazu , Shibata Masahiro , Nakatsuka Takashi , Ando Joji , Ueno Shoogo
Published: August 2003

High intensity static magnetic fields, when applied to the whole body of the anesthetized rat, have previously been reported to decrease skin temperature. The hypothesis of the present study was that in diamagnetic water, molecules in the air play significant roles in the mechanism of skin temperature decrease. We used a horizontal cylindrical superconducting magnet. The magnet produced 8 T at its center. A thermistor probe was inserted in a subcutaneous pocket of the anesthetized rats to measure skin temperature. Animals (n=10) were placed in an open plastic holder in which the ambient air was free to move in any direction (group I). Animals (n=10) were placed in a closed holder in which the air circulation toward the direction of weak magnetic field was restricted (group II). Each holder was connected to a hydrometer to measure humidity around the animal in the holder. The data acquisition phase consisted of a 5 min baseline interval, followed by inserting the animal together with the holder into the center of the magnet bore for a 5 min exposure and a 5 min postexposure period outside the bore. In group I, skin temperature and humidity around the animal significantly decreased during exposure, followed by recovery after exposure. In group II, skin temperature and humidity did not decrease during the measurement. The skin temperature decrease was closely related to the decrease in humidity around the body of the animal in the holder, and the changes were completely blocked by restricting the air circulation in the direction of the bore entrance. Possible mechanisms responsible for the decrease in skin temperature may be associated with magnetically induced movement of water vapor at the skin surface, leading to skin temperature decrease. Bioelectromagnetics 24:380–386, 2003. © 2003 Wiley‐Liss, Inc.
Effects of different intensities of extremely low frequency pulsed electromagnetic fields on formation of osteoclast‐like cells
Authors: Chang Kyle , Chang Walter Hong‐Shong , Wu Mei‐Ling , Shih Chung
Published: August 2003

Over the past 30 years, the beneficial therapeutic effects of selected low energy, time varying electromagnetic fields (EMF) have been documented with increasing frequency to treat therapeutically resistant problems of the musculoskeletal system. However, the underlying mechanisms at a cellular level are still not completely understood. In this study, the effects of extremely low frequency pulsed electromagnetic fields (ELF‐PEMF) on osteoclastogenesis, cultured from murine bone marrow cells and stimulated by 1,25(OH)2D3, were examined. Primary bone marrow cells were cultured from mature Wistar rats and exposed to ELF‐PEMF stimulation daily for 7 days with different intensities of induced electric field (4.8, 8.7, and 12.2 μV/cm rms) and stimulation times (0.5, 2, and 8 h/day). Recruitment and authentication of osteoclast‐like cells were evaluated, respectively, by determining multinuclear, tartrate resistant acid phosphatase (TRAP) positive cells on day 8 of culture and by the pit formation assay. During the experiments, cytokines such as tumor necrosis factor‐α (TNF‐α), interleukin 1‐β (IL‐1β), and prostaglandin‐E2 (PGE2) were assayed using the enzyme linked immunosorbent assay (ELISA). These findings suggest that ELF‐PEMF can both enhance (approximately 50%) and suppress (approximately 27%) the formation of osteoclast‐like cells in bone marrow culture, depending on the induced electric field intensity. In addition, consistent correlations were observed between TNF‐α, IL‐1β, and osteoclast‐like cell number after exposure to different induced electric field intensities of ELF‐PEMF. This in vitro study could be considered as groundwork for in vivo ELF‐PEMF clinical applications on some osteoclast‐associated bone diseases. Bioelectromagnetics 24:431–439, 2003. © 2003 Wiley‐Liss, Inc.
Dielectric properties of porcine brain tissue in the transition from life to death at frequencies from 800 to 1900 MHz
Authors: Schmid Gernot , Neubauer Georg , Illievich Udo M. , Alesch François
Published: August 2003

Ten experiments on pigs were performed to investigate possible postmortem changes of the dielectric properties of brain gray matter in the frequency range of 800–1900 MHz. After keeping the animals in stable anaesthesia for at least 45 min, they were euthanatised by an intravenous injection of hypertonic potassium chloride (KCl), causing cardiac arrest within 3 min. Measurements of the dielectric properties were performed repeatedly from at least 45 min prior to death to 18 h after euthanasia. The anaesthesia regimen was chosen to minimize influence on brain tissue characteristics such as brain water content, intracranial blood volume, and cerebral blood flow. The data showed a decline of mean gray matter equivalent conductivity of about 15% at 900 MHz and about 11% at 1800 MHz within the first hour after death. The decline in permittivity was less pronounced (about 3–4%) and almost frequency independent. The results indicate that in vitro measurements of dielectric properties of brain tissue underestimate equivalent conductivity as well as permittivity of living tissue. These changes may affect the generally accepted data of dielectric properties of brain tissue widely used in RF dosimetry. Bioelectromagnetics 24:413–422, 2003. © 2003 Wiley‐Liss, Inc.
Dielectric properties of human brain tissue measured less than 10 h postmortem at frequencies from 800 to 2450 MHz
Authors: Schmid Gernot , Neubauer Georg , Mazal Peter R.
Published: August 2003

The dielectric properties of gray matter in the frequency range of 800–2450 MHz were measured on 20 human brains immediately after excision, less than 10 h after death. The brains were obtained during autopsy of 10 male and 10 female humans who died at ages between 47.5 and 87.5 years [70.4 ± 9.8 years, mean ± standard deviation (SD)]. The tissue temperature at the measurement sites ranged between 18 and 25 °C (21.35 ± 1.6 °C, mean ± SD). On each brain, four specific locations on the temporal lobe were measured on the right and left sides, i.e., 160 different measurements of the dielectric properties were performed. The dielectric probe was placed on the intact arachnoid on a gyrus in the selected area. The measurements yielded a mean value (±SD) of gray matter equivalent conductivity of 1.13 ± 0.12 and 2.09 ± 0.16 S/m at 800 and 2450 MHz, respectively. The mean value of measured relative permittivity was 58.2 ± 3.3 and 54.7 ± 3.3 at 800 and 2450 MHz, respectively. Taking into account a positive temperature coefficient of equivalent conductivity, these measurements indicate that the equivalent conductivity of human gray matter at body temperature is somewhat higher than today's generally accepted value, which is based on measurements on animal tissue and excised samples of human tissue measured more than 24 h postmortem. Bioelectromagnetics 24:423–430, 2003. © 2003 Wiley‐Liss, Inc.
Interaction between weak low frequency magnetic fields and cell membranes
Authors: Bauréus Koch C.L.M. , Sommarin M. , Persson B.R.R. , Salford L.G. , Eberhardt J.L.
Published: August 2003

The question of whether very weak low frequency magnetic fields can affect biological systems, has attracted attention by many research groups for quite some time. Still, today, the theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely low frequency (ELF) magnetic fields on the transport of Ca2+ was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested two quantum mechanical theoretical models that assume that biologically active ions can be bound to a channel protein and influence the opening state of the channel. Vesicles were exposed for 30 min at 32 °C and the calcium efflux was studied using radioactive 45Ca as a tracer. Static magnetic fields ranging from 27 to 37 μT and time varying magnetic fields with frequencies between 7 and 72 Hz and amplitudes between 13 and 114 μT (peak) were used. We show that suitable combinations of static and time varying magnetic fields directly interact with the Ca2+ channel protein in the cell membrane, and we could quantitatively confirm the model proposed by Blanchard. Bioelectromagnetics 24:395–402, 2003. © 2003 Wiley‐Liss, Inc.
Electrosensibility and electromagnetic hypersensitivity
Authors: Leitgeb Norbert , Schröttner Jörg
Published: August 2003

Electromagnetic sensibility, the ability to perceive electric and electromagnetic exposure, and electromagnetic hypersensitivity (EHS), developing health symptoms due to exposure to environmental electromagnetic fields, need to be distinguished. Increased electrosensibility is a necessary, however, not a sufficient condition for electromagnetic hypersensitivity. At an extended sample of the general population of 708 adults, including 349 men and 359 women aged between 17 and 60 years, electrosensibility was investigated and characterized by perception threshold and its standard deviation. By analyzing the probability distributions of the perception threshold of electric 50 Hz currents, evidence could be found for the existence of a subgroup of people with significantly increased electrosensibility (hypersensibility) who as a group could be differentiated from the general population. The presented data show that the variation of the electrosensibility among the general population is significantly larger than has yet been estimated by nonionizing radiation protection bodies, but much smaller than claimed by hypersensitivity self‐aid groups. These quantitative results should contribute to a less emotional discussion of this problem. The investigation method presented, is capable of exclusion diagnostics for persons suffering from the hypersensitivity syndrome. Bioelectromagnetics 24:387–394, 2003. © 2003 Wiley‐Liss, Inc.
Effects of static magnetic fields on plasma levels of angiotensin II and aldosterone associated with arterial blood pressure in genetically hypertensive rats
Authors: Okano Hideyuki , Ohkubo Chiyoji
Published: August 2003

Effects of static magnetic fields (SMFs) on development of hypertension were investigated using young male, stroke resistant, spontaneously hypertensive rats (SHRs) beginning at 7 weeks of age. SHRs were randomly assigned to two different exposure groups or an unexposed group. The SHRs in the exposure groups were constantly exposed to two different types of external SMFs of 3.0–10.0 mT or 8.0–25.0 mT for 12 weeks. The SMFs were generated from permanent magnetic plates attached to the rat cage. The blood pressure (BP) of each rat was determined at weekly intervals using indirect tail‐cuff method. The SMFs suppressed and retarded the development of hypertension in both exposed groups to a statistically significant extent for several weeks, as compared with an unexposed group. The antipressor effects were related to the extent of reduction in plasma levels of angiotensin II and aldosterone in the SHRs. These results suggest that the SMFs of mT intensities with spatial gradients could be attributable to suppression of early BP elevation via hormonal regulatory system. Bioelectromagnetics 24:403–412, 2003. © 2003 Wiley‐Liss, Inc.
Eine handgreifliche Geschichtslüge. Wie Martin Luther zum Gegner des copernicanischen Weltsystems gemacht wurde.
Authors: Kleinert Andreas
Published: August 2003

Martin Luther has been severely criticized for an offhand remark about Copernicus. In the most frequently cited version of this statement, Luther is alledged to have branded Copernicus as a fool who will turn the whole science of astronomy upside down. This disparaging judgment on Luther prevails in many publications by respected historians of science of the 20th century, although since the early thirties, it has been convincingly demonstrated that the famous citation from Luther's table talk is next to worthless as an historical source, that Luther never referred to Copernicus or to the heliocentric world system in all of his voluminous writings, and that there is no indication that Luther ever suppressed the Copernican viewpoint. His attitude towards Copernicus was indifference or ignorance, but not hostility. In this paper, it is shown that the story of Luther's anti‐Copernicanism emerged in the second half of the 19th century. It was invented by Franz Beckmann and Franz Hipler, two Prussian Catholic historians who were engaged in the conflict between the German government under Bismarck and the Catholic Church (Kulturkampf), and it was disseminated by influential German and American historians like Leopold Prowe, Ernst Zinner, and Andrew D. White. In the second half of the 20th century, many historians of science relied on the authority of these authors, rather than studying the sources or the secondary literature in which it has been proved that Luther's anti‐Copernicanism is an outright falsification of history.
Die Rezeption der humanistischen Gedächtnislehre bei Luther: Natur, Kunst und Konfessionen
Authors: Rieke‐Müller Annelore
Published: August 2003

Iconoclasm is one of the central characteristic of the reformation movement. In several books it was argued that there was a connection between iconoclasm and the interpretation of nature as a language and as a text since about 1600. This article discusses the artist as a creator in Renaissance culture. It shows the reaction of Luther to this concept and to iconoclasm, focussing on the connection between the Lutheran control of pictures and images and his conception of the mind and of memory on the one hand and of creatures as images and natural history on the other. In Lutheran context the book of nature was a book made of images as signs of the word of God.
Zwischen Trient und Vatikanum II: Der Fall Galilei
Authors: Segre Michael
Published: August 2003

The Council of Trent and the Second Vatican Council are significant both to Lutheranism and Science. The first inaugurated the Counter Reformation and formulated a decree related to biblical hermeneutics (1546) later used as a basis for Galileo's condemnation. The second modernized the Roman Catholic Church and formulated the Pastoral Constitution Gaudium et spes (1964) used by Pope John Paul II as a basis for the reconsideration of the condemnation. In both cases, however, the Church of Rome may not have followed the spirit of its councils. In the 17th century it condemned Galileo following a radical interpretation of the teaching of Trent, that of Cardinal Robert Bellarmine (now a saint). Recently it reconsidered the ‚Affair’︁ unsatisfactorily probably because Gaudium et spes encouragement of science clashes with the possibility that Saint Bellarmine misinterpreted the Trent decree.
Christus als Apotheker bei Martin Luther. Zugleich ein Beitrag zum Gespräch mit Fritz Krafft.
Authors: Anselm Steiger Johann
Published: August 2003

This contribution has been stimulated by the latest study written by Fritz Krafft concerning the motif “Jesus Christ as a pharmacist”, which was frequently used in Christian art. It is shown that this motif, fully developed in the first third of the 17th century, originated in the theology of Martin Luther.
Reformation(en) und Wissenschaft(en). Einführung in das Tagungsthema
Authors: Meinel Christoph
Published: August 2003

Based on a brief historiographical survey, the article aims at tracing some intellectual relationships between early modern science and the protestant Reformation (or the various individual reformations underlying it). Besides the mere structural analogies of the two reform movements and their common debt to Renaissance humanism, common elements such as the new reading of texts and the new role of the individual, but also the philosophical link between voluntarism and the notion of natural law, are discussed. However, the ambiguous attitude towards natural knowledge and the wide variety within the European protestant movement ask for a much closer look into the relationships between science and the Reformation than has been hitherto been achieved.
Die zweite Welle der Wiederaneignung des Corpus Aristotelicum in der frühen Neuzeit: die ethische und politische Tradition. Ein Forschungsbericht
Authors: Frank Günter
Published: August 2003

This paper presents a general view over the second reception of Aristotle's writings beginning after the first invasion of Western crusaders in Constantinople in 1204 and enforced after the fall of the Byzantine capital in 1453. After the turn of the century we observe a widespread commentary tradition of Aristotle's writings, particularily of his Ethics and Politics. Philipp Melanchthon became the leading figure in these ethical and political discussions. More than 53 of his works relating this which were printed within the 16th century are known.
Hox genes and the crustacean body plan
Authors: Deutsch Jean S. , Mouchel‐Vielh Emmanuèle
Published: August 2003

The Crustacea present a variety of body plans not encountered in any other class or phylum of the Metazoa. Here we review our current knowledge on the complement and expression of the Hox genes in Crustacea, addressing questions related to the evolution of body architecture. Specifically, we discuss the molecular mechanisms underlying the homeotic transformation of legs into feeding appendages, which occurred in parallel in several branches of the crustacean evolutionary tree. A second issue that can be approached by the comparative study of Hox genes and their expression in the Crustacea bears on the homology of the abdomen. We discuss whether the so‐called “abdominal” tagma of the crustaceans is homologous to the abdomen of insects. In addition, the homology of the abdomen between malacostracan and non‐malacostracan crustaceans has also been questioned. We also address the question of the molecular developmental basis of the apparent lack of an abdomen in barnacles. We discuss these issues in relation to the problem of constraint versus adaptation in evolution. BioEssays 25:878–887, 2003. © 2003 Wiley Periodicals, Inc.
Evolving questions and paradigm shifts in endoplasmic‐reticulum‐associated degradation (ERAD)
Authors: McCracken Ardythe A. , Brodsky Jeffrey L.
Published: August 2003

ER‐associated degradation (ERAD) is a component of the protein quality control system, ensuring that aberrant polypeptides cannot transit through the secretory pathway. This is accomplished by a complex sequence of events in which unwanted proteins are selected in the ER and exported to the cytosol for degradation by the proteasome. Given that protein quality control can be essential for cell survival, it is not surprising that ERAD is linked to numerous disease states. Here we review the molecular mechanisms of ERAD, its role in metabolic regulation and biomedical implications, and the unanswered questions regarding this process. BioEssays 25:868–877, 2003. © 2003 Wiley Periodicals, Inc.
More than the sum of their parts: On the evolution of proteins from peptides
Authors: Söding Johannes , Lupas Andrei N.
Published: August 2003

Despite their seemingly endless diversity, proteins adopt a limited number of structural forms. It has been estimated that 80% of proteins will be found to adopt one of only about 400 folds, most of which are already known. These folds are largely formed by a limited ‘vocabulary’ of recurring supersecondary structure elements, often by repetition of the same element and, increasingly, elements similar in both structure and sequence are discovered. This suggests that modern proteins evolved by fusion and recombination from a more ancient peptide world and that many of the core folds observed today may contain homologous building blocks. The peptides forming these building blocks would not in themselves have had the ability to fold, but would have emerged as cofactors supporting RNA‐based replication and catalysis (the ‘RNA world’). Their association into larger structures and eventual fusion into polypeptide chains would have allowed them to become independent of their RNA scaffold, leading to the evolution of a novel type of macromolecule: the folded protein. BioEssays 25:837–846, 2003. © 2003 Wiley Periodicals, Inc.
Intrinsically unstructured proteins evolve by repeat expansion
Authors: Tompa Peter
Published: August 2003

The proportion of the genome encoding intrinsically unstructured proteins increases with the complexity of organisms, which demands specific mechanism(s) for generating novel genetic material of this sort. Here it is suggested that one such mechanism is the expansion of internal repeat regions, i.e., coding micro‐ and minisatellites. An analysis of 126 known unstructured sequences shows the preponderance of repeats: the percentage of proteins with tandemly repeated short segments is much higher in this class (39%) than earlier reported for all Swiss‐Prot (14%), yeast (18%) or human (28%) proteins. Furthermore, prime examples, such as salivary proline‐rich proteins, titin, eukaryotic RNA polymerase II, the prion protein and several others, demonstrate that the repetitive segments carry fundamental function in these proteins. In addition, their repeat numbers show functionally significant interspecies variation and polymorphism, which underlines that these regions have been shaped by intense evolutionary activity. In all, the major point of this paper is that the genetic instability of repetitive regions combined with the structurally and functionally permissive nature of unstructured proteins has powered the extension and possible functional expansion of this newly recognized protein class. BioEssays 25:847–855, 2003. © 2003 Wiley Periodicals, Inc.
Zebrafish: A new model on the pharmaceutical catwalk
Authors: Langheinrich Ulrike
Published: August 2003

Zebrafish is recognized as one of the most important vertebrate model organisms; however, its value in pharmacological studies has not been extensively explored and exploited. In this review, I summarize significant findings about the effects of drugs and medicines on important physiological processes in zebrafish. Our experiments have shown that cardiovascular, anti‐angiogenic and anti‐cancer drugs elicit comparable responses in zebrafish embryos to those in mammalian systems. Similar observations have been reported by other laboratories, exposing zebrafish to a variety of pharmaceutical active compounds affecting a range of different processes. All the data summarized indicate that zebrafish represents a very valuable organism for different kinds of pharmacological studies, such as screenings of chemical libraries, lead validation and optimization, mode‐of‐action studies, analysis of gene function, predictive toxicology and teratogenicity, pharmacogenomics and toxicogenomics. Zebrafish pharmacological assays have specific advantages compared to in vitro cell culture studies and in vivo experiments using mice, complementing these assays to give valuable guides for future tests of new drugs for human therapy. BioEssays 25:904–912, 2003. © 2003 Wiley Periodicals, Inc.
Cell‐cycle‐regulatory elements and the control of cell differentiation in the budding yeast
Authors: Wittenberg Curt , La Valle Roberto
Published: August 2003

The stable differentiation of cells into other cell types typically involves dramatic reorganization of cellular structures and functions. This often includes remodeling of the cell cycle and the apparatus that controls it. Here we review our understanding of the role and regulation of cell cycle control elements during cell differentiation in the yeast, Saccharomyces cerevisiae. Although the process of differentiation may be more overtly obvious in metazoan organisms, those systems are by nature more difficult to study at a mechanistic level. We consider the relatively well‐understood mechanisms by which mating‐type switching and the pheromone‐induced differentiation of gametes are coupled to the cell cycle as well as the more obscure mechanisms that govern the remodeling of the cell cycle during meiosis and filamentous growth. In some cases, the cell cycle is a primary stimulus for differentiation whereas, in other cases, the signals that promote differentiation alter the cell cycle. Thus, despite relative simplicity of these processes in yeast, the nature of the interplay between the cell cycle and differentiation is diverse. BioEssays 25:856–867, 2003. © 2003 Wiley Periodicals, Inc.
Collective specification of cellular development
Authors: Sachs Tsvi
Published: August 2003

Studies of chimeras and in vivo development demonstrate that cell lineages are often quite variable, apparently in response to chance perturbations. This points to an apparent contradiction: although individual cells are the units of genetic information and differentiation, not all cellular events need be precise for the development of functional organisms. The social organization of ants can serve as a metaphor that helps understand the mechanisms that underlie such development. Ants suggest that continued cellular interactions and environmental conditions could specify the proportion and general location of specialized units. Leaf venation is used as a concrete example of this general principle. A signal produced continuously by all cells specifies a requirement for vein differentiation. The cells that respond by differentiation then transport the signal away from the leaf; this removal acting as a feedback indicating that the requirement is being met. Because transport increases during vein differentiation, early initiation occurs in excess and vein ‘competition’ for the signal assures an acceptable outcome. Such specification would be robust since it does not depend on events in any single cell, and chance events, rather than being corrected or reversed, may be built upon in reaching an expected, collective phenotype. The absence of detailed information preceding development distinguishes this hypothesis from the common alternatives of a program or blueprint. Collective specification would have important implications for developmental plasticity and evolution. BioEssays 25:897–903, 2003. © 2003 Wiley Periodicals, Inc.
Apoptosis—an introduction
Authors: Lawen Alfons
Published: August 2003

Apoptosis has become a major research area in the biomedical sciences. As there are more than 13,000 papers published annually on the topic, it is impossible to keep track on all developments in the area. The individual aspects of molecular control of apoptosis are well reviewed, but more general, introductory recent reviews into the field are lacking. This review aims to give a brief overview of the field, providing an introduction into the literature for students and newcomers; as it is written for the un‐initiated, wherever possible, review articles will be cited rather than original papers. BioEssays 25:888–896, 2003. © 2003 Wiley Periodicals, Inc.
Evolution of flowering in response to day length: Flipping the CONSTANS switch
Authors: Simpson Gordon G.
Published: August 2003

Day length provides an important environmental cue by signalling conditions favourable for flowering. While Arabidopsis promotes flowering in response to long days, rice promotes flowering in response to short days. Despite this difference, a recent paper reveals that the network controlling this response is highly conserved in these distantly related plants, only the activity of one component is reversed.1 This reveals how an important developmental process can be diversified for adaptation by using the same set of genes, but regulating them differently. BioEssays 25:829–832, 2003. © 2003 Wiley Periodicals, Inc.
Mum, this bud's for you: Where do you want it? roles for Cdc42 in controlling bud site selection in Saccharomyces cerevisiae
Authors: Nelson W. James
Published: August 2003

The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,1,2 but a recent paper has also raised questions about how control of Cdc42 activity is integrated into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.3 BioEssays 25:833–836, 2003. © 2003 Wiley Periodicals, Inc.
From genes to therapeutics: Educating the government and the public on biomedical sciences—a Singapore experience
Authors: Phon Too Heng
Published: August 2003

Singapore has a highly developed economy and has been recognized to have one of the best business environments in Asia. Her success is based largely on focused developments of key industries in traded services and manufacturing sectors. The challenge for Singapore is to utilize her small human resource to transform the present economy to a more knowledge‐intensive economy. Singapore has recently embarked on the ambitious goal of developing Biomedical Sciences as an industry. Educating the government and the public on various aspects of this new industry was identified as one of the essential steps towards this goal. The challenge was to inspire non‐biologists to embrace the life sciences. This review describes how a series of workshops were developed to address the needs and the challenges of educating the public and the government. BioEssays 25:913–917, 2003. © 2003 Wiley Periodicals, Inc.
Chemical and functional diversity of small molecule ligands for RNA
Authors: Hermann Thomas
Published: August 2003

Functional RNAs such as ribosomal RNA and structured domains of mRNA are targets for small molecule ligands that can act as modulators of the RNA biological activity. Natural ligands for RNA display a bewildering structural and chemical complexity that has yet to be matched by synthetic RNA binders. Comparison of natural and artificial ligands for RNA may help to direct future approaches to design and synthesize potent novel scaffolds for specific recognition of RNA targets. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Thermodynamics of aminoglycoside–rRNA recognition
Authors: Pilch Daniel S. , Kaul Malvika , Barbieri Christopher M. , Kerrigan John E.
Published: August 2003

2‐Deoxystreptamine (2‐DOS) aminoglycosides are a family of structurally related broad‐spectrum antibiotics that are used widely in the treatment of infections caused by aerobic Gram‐negative bacilli. Their antibiotic activities are ascribed to their abilities to bind a highly conserved A site in the 16 S rRNA of the 30 S ribosomal subunit and interfere with protein synthesis. The abilities of the 2‐DOS aminoglycosides to recognize a specific subdomain of a large RNA molecule make these compounds archetypical models for RNA‐targeting drugs. This article presents a series of calorimetric, spectroscopic, osmotic stress, and computational studies designed to evaluate the thermodynamics (ΔG, ΔH, ΔS, ΔCp) of aminoglycoside–rRNA interactions, as well as the hydration changes that accompany these interactions. In conjunction with the current structural database, the results of these studies provide important insights into the molecular forces that dictate and control the rRNA binding affinities and specificities of the aminoglycosides. Significantly, identification of these molecular driving forces [which include binding‐linked drug protonation reactions, polyelectrolyte contributions from counterion release, conformational changes, hydration effects, and molecular interactions (e.g., hydrogen bonds and van der Waals interactions)], as well as the relative magnitudes of their contributions to the binding free energy, could not be achieved by consideration of structural data alone, highlighting the importance of acquiring both thermodynamic and structural information for developing a complete understanding of the drug–RNA binding process. The results presented here begin to establish a database that can be used to predict, over a range of conditions, the relative affinity of a given aminoglycoside or aminoglycoside mimetic for a targeted RNA site vs binding to potential competing secondary sites. This type of predictive capability is essential for establishment of a rational design approach to the development of new RNA‐targeted drugs. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Ribosomal crystallography: Peptide bond formation and its inhibition
Authors: Bashan Anat , Zarivach Raz , Schluenzen Frank , Agmon Ilana , Harms Joerg , Auerbach Tamar , Baram David , Berisio Rita , Bartels Heike , Hansen Harly A. S. , Fucini Paola , Wilson Daniel , Peretz Moshe , Kessler Maggie , Yonath Ada
Published: August 2003

Ribosomes, the universal cellular organelles catalyzing the translation of genetic code into proteins, are protein/RNA assemblies, of a molecular weight 2.5 mega Daltons or higher. They are built of two subunits that associate for performing protein biosynthesis. The large subunit creates the peptide bond and provides the path for emerging proteins. The small has key roles in initiating the process and controlling its fidelity.

Crystallographic studies on complexes of the small and the large eubacterial ribosomal subunits with substrate analogs, antibiotics, and inhibitors confirmed that the ribosomal RNA governs most of its activities, and indicated that the main catalytic contribution of the ribosome is the precise positioning and alignment of its substrates, the tRNA molecules.

A symmetry‐related region of a significant size, containing about two hundred nucleotides, was revealed in all known structures of the large ribosomal subunit, despite the asymmetric nature of the ribosome. The symmetry rotation axis, identified in the middle of the peptide‐bond formation site, coincides with the bond connecting the tRNA double‐helical features with its single‐stranded 3′ end, which is the moiety carrying the amino acids. This thus implies sovereign movements of tRNA features and suggests that tRNA translocation involves a rotatory motion within the ribosomal active site.

This motion is guided and anchored by ribosomal nucleotides belonging to the active site walls, and results in geometry suitable for peptide‐bond formation with no significant rearrangements. The sole geometrical requirement for this proposed mechanism is that the initial P‐site tRNA adopts the flipped orientation.

The rotatory motion is the major component of unified machinery for peptide‐bond formation, translocation, and nascent protein progression, since its spiral nature ensures the entrance of the nascent peptide into the ribosomal exit tunnel. This tunnel, assumed to be a passive path for the growing chains, was found to be involved dynamically in gating and discrimination. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003