bluuebunny/crossref_metadata_2025 huggingface dataset:
A unified model for the origin of DNA sequence‐directed curvature
Authors: Hud Nicholas V. , Plavec Janez
Published: April 2003

The fine structure of the DNA double helix and a number of its physical properties depend upon nucleotide sequence. This includes minor groove width, the propensity to undergo the B‐form to A‐form transition, sequence‐directed curvature, and cation localization. Despite the multitude of studies conducted on DNA, it is still difficult to appreciate how these fundamental properties are linked to each other at the level of nucleotide sequence. We demonstrate that several sequence‐dependent properties of DNA can be attributed, at least in part, to the sequence‐specific localization of cations in the major and minor grooves. We also show that effects of cation localization on DNA structure are easier to understand if we divide all DNA sequences into three principal groups: A‐tracts, G‐tracts, and generic DNA. The A‐tract group of sequences has a peculiar helical structure (i.e., B*‐form) with an unusually narrow minor groove and high base‐pair propeller twist. Both experimental and theoretical studies have provided evidence that the B*‐form helical structure of A‐tracts requires cations to be localized in the minor groove. G‐tracts, on the other hand, have a propensity to undergo the B‐form to A‐form transition with increasing ionic strength. This property of G‐tracts is directly connected to the observation that cations are preferentially localized in the major groove of G‐tract sequences. Generic DNA, which represents the vast majority of DNA sequences, has a more balanced occupation of the major and minor grooves by cations than A‐tracts or G‐tracts and is thereby stabilized in the canonical B‐form helix. Thus, DNA secondary structure can be viewed as atug of warbetween the major and minor grooves for cations, with A‐tracts and G‐tracts each having one groove that dominates the other for cation localization. Finally, the sequence‐directed curvature caused by A‐tracts and G‐tracts can, in both cases, be explained by the cation‐dependent mismatch of A‐tract and G‐tract helical structures with the canonical B‐form helix of generic DNA (i.e., a cation‐dependent junction model). © 2003 Wiley Periodicals, Inc. Biopolymers 69: 144–159, 2003
Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract
Authors: Nogué‐Aliguer Miquel , Carles Joan , Arrivi Antonio , Juan Oscar , Alonso Lorenzo , Font Albert , Mellado Begoña , Garrido Pilar , Sáenz Alberto
Published: April 2003

BACKGROUND

Cisplatin‐based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative.

METHODS

Patients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m2 on Days 1 and 8 and carboplatin area under the concentration‐time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled.

RESULTS

A total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1–8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6–71.6%). Progression‐free survival was 7.2 months (95% CI, 5.7–8.5) and median survival was 10.1 months (95% CI, 8.8–12.2).

CONCLUSIONS

The combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated. Cancer 2003;97:2180–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.10990
A multigene test for the risk of sporadic breast carcinoma
Authors: Comings David E. , Gade‐Andavolu Radhika , Cone Lawrence A. , Muhleman Donn , MacMurray James P.
Published: April 2003

BACKGROUND

Although the identification of the BRCA1 and BRCA2 genes have been of great interest, these genes account for less than 5% of all breast carcinoma cases. The remaining cases are sporadic. Reanalysis of a large twin study suggested that genetic factors may play a significant role in sporadic breast and other carcinomas. Sporadic breast carcinoma is polygenically inherited. Multiple genes are likely to have an additive effect, each gene accounting for a fraction of the variance. One factor that may have an impact on the development of hormonally responsive breast tumors is the duration of exposure of the breast to estrogen. Therefore, one of the demographic risk factors for breast carcinoma is an early age of onset of menarche. The current study was based on the hypothesis that genes that play a role in demographic risk factors may be breast carcinoma risk genes in their own right. The authors hypothesized that six genes relevant to the timing of the onset of menarche and related risk factors might be candidate genes for breast carcinoma. These were the leptin gene (LEP), the leptin receptor gene (LEPR), the catechol‐0‐methyltransferase gene (COMT), the dopamine D2 receptor gene (DRD2), the estrogen 1 receptor gene (ESR1), and the androgen receptor gene (AR).

METHODS

The authors examined 67 women with postmenopausal sporadic breast carcinoma and 145 gender and race‐matched controls.

RESULTS

Five of these genes accounted for a significant percent of the variance (r2) of breast carcinoma. The following r2 and P values were calculated: LEP: 0.073, P ≤ 0.0001; LEPR: 0.064, P ≤ 0.0002; COMT: 0.073, P ≤ 0.0001; AR: 0.040, P ≤ 0.0035; and DRD2: 0.018, P ≤ 0.05. When evaluated in a multivariate regression analysis, they accounted collectively for 24% of the variance of breast carcinoma (P ≤ 0.0001). These genes accounted for 40% of the variance (P ≤ 0.00001) in a subset of age‐matched cases. Individual gene scores were added to form a breast carcinoma risk score (BCRS) that ranged from 0 to 17. When the BCRS was evaluated in a receiver operator characteristic plot, the area under the curve was 0.80 for the full set and 0.869 for the age‐matched set. The relative breast carcinoma risk for the different BCRS scores ranged from 0.10 to 11.9.

CONCLUSIONS

These results demonstrate a potentially powerful method of evaluating the additive effect of multiple breast carcinoma risk genes to form a potentially clinically useful assessment of women's risk for sporadic breast carcinoma. Cancer 2003;97:2160–70. © 2003 American Cancer Society.

DOI 10.1002/cncr.11340
Large cholinergic nerve terminals on subsets of motoneurons and their relation to muscarinic receptor type 2
Authors: Hellström Johan , Oliveira Alexandre L.R. , Meister Björn , Cullheim Staffan
Published: April 2003

The cholinergic C‐bouton is a large nerve terminal found exclusively apposing motoneuron cell somata and proximal dendrites. The origin and function of the C‐bouton is not known. An antiserum against the vesicular acetylcholine transporter was used to identify large cholinergic nerve terminals putatively of the C‐type in close apposition to motoneuron cell somata. This type of nerve terminal was present in the rat spinal cord ventral horn, but only in some cranial motor nuclei. Fluoro‐Gold tracing showed that subsets of spinal motoneuron cell somata were contacted by different numbers of putative C‐boutons. Thus, motoneurons innervating an intrinsic foot muscle were contacted by about half the number of cholinergic terminals found on motoneurons of the predominantly fast‐twitch gastrocnemius muscle. Slow‐twitch soleus motoneurons showed an intermediate innervation. There was a strong correlation between the presence of putative C‐boutons and muscarinic receptor 2 (m2)‐like immunoreactivity (‐LI) within a motor nucleus. By using confocal laser microscopy, the m2‐LI appeared to be confined to the motoneuron cell membrane and strongly enriched beneath the C‐type nerve terminal. Thus, our results suggested a differential distribution of large cholinergic C‐boutons, depending on motoneuron type, and that the presence of this nerve terminal type is associated with m2‐LI in the postsynaptic membrane. J. Comp. Neurol. 460:476–486, 2003. © 2003 Wiley‐Liss, Inc.
Spatiotemporal distribution of neuronal calcium sensor‐1 in the developing rat spinal cord
Authors: Kawasaki Takayuki , Nishio Takeshi , Kurosawa Hisashi , Roder John , Jeromin Andreas
Published: April 2003

The present study revealed the localization of neuronal calcium sensor (NCS)‐1 immunoreactivity (IR) in the developing rat spinal cord. The NCS‐1 IR first appeared at embryonic day 12 in the peripheral nerves and their somata. Intense NCS‐1 IR was expressed in ascending and descending tracts in the white matter during the late prenatal period, which gradually decreased to the faint level during postnatal development. Intense NCS‐1 IR was colocalized with growth associated protein (GAP)‐43 IR in the marginal zone and with the glutamate‐aspartate transporter (GLAST) IR in the radial processes traversing the marginal zone. In the adult rat white matter, radially oriented astrocytes and astrocytes in the glia limitans were double‐labeled for NCS‐1 and glial fibrillary acidic protein (GFAP), whereas small dots on finger‐like dendritic projections were double‐labeled for NCS‐1 and synaptophysin. In the developing gray matter, the NCS‐1 IR appeared at embryonic day 12 and gradually increased in the neuronal somata and neuropil, reaching a plateau after the end of the 4th postnatal week. The small dots in neuropil were colabeled for NCS‐1 and GFAP or NCS‐1 and synaptophysin in the adult rat gray matter. These results strongly suggest that NCS‐1 is involved in axogenesis and synaptogenesis in the developing rat spinal cord. NCS‐1 can serve as a Ca2+‐sensor not only in neurons but also in radial glial cells or even in radially oriented astrocytes in the adult rat spinal cord. J. Comp. Neurol. 460:465–475, 2003. © 2003 Wiley‐Liss, Inc.
Nectin‐dependent localization of ZO‐1 at puncta adhaerentia junctions between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of adult mouse hippocampus
Authors: Inagaki Maiko , Irie Kenji , Deguchi‐Tawarada Maki , Ikeda Wataru , Ohtsuka Toshihisa , Takeuchi Masakazu , Takai Yoshimi
Published: April 2003

Nectin and afadin constitute a novel intercellular adhesion system that organizes adherens junctions in cooperation with the cadherin‐catenin system in epithelial cells. Nectin is a Ca2+‐independent immunoglobulin‐like adhesion molecule and afadin is an actin filament (F‐actin)‐binding protein that connects nectin to the actin cytoskeleton. At the puncta adhaerentia junctions (PAs) between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, the nectin‐afadin system also colocalizes with the cadherin‐catenin system and has a role in the formation of synapses. ZO‐1 is another F‐actin‐binding protein that localizes at tight junctions (TJs) and connects claudin to the actin cytoskeleton in epithelial cells. The nectin‐afadin system is able to recruit ZO‐1 to the nectin‐based cell–cell adhesion sites in nonepithelial cells that have no TJs. In the present study, we investigated the localization of ZO‐1 in the mouse hippocampus. Immunofluorescence and immunoelectron microscopy revealed that ZO‐1 also localized at the PAs between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, as described for afadin. ZO‐1 colocalized with afadin during the development of synaptic junctions and PAs. Microbeads coated with the extracellular fragment of nectin, which interacts with cellular nectin, recruited both afadin and ZO‐1 to the bead–cell contact sites in cultured rat hippocampal neurons. These results indicate that ZO‐1 colocalizes with nectin and afadin at the PAs and that the nectin‐afadin system is involved in the localization of ZO‐1. J. Comp. Neurol. 460:514–524, 2003. © 2003 Wiley‐Liss, Inc.
Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis Domestica)
Authors: Ek Carl Joakim , Habgood Mark David , Dziegielewska Katarzyna Magdalena , Saunders Norman Ruthven
Published: April 2003

The structural and functional development of the choroid plexuses, the site of the blood‐cerebrospinal fluid (CSF) barrier, in an opossum (Monodelphis domestica) was studied. Marsupial species are extremely immature at birth compared with more conventional eutherian species. Choroid plexus tissue of each brain ventricle, from early stages of development, was collected for light and electron microscopy. During development, the choroidal epithelium changes from a pseudostratified to a cuboidal layer. Individual epithelial cells appear to go through a similar maturation process even though the timing is different between and within each plexus. The ultrastructural changes during development in the choroidal epithelial cells consist of an increase in the number of mitochondria and microvilli, and changes in structure of endoplasmic reticulum. There are also changes in the core of plexuses with age. In contrast, the structure of the tight junctions between epithelial cells does not appear to change with maturation. In addition, the route of penetration for lipid insoluble molecules from blood to CSF across the choroid plexuses was examined using a small biotin‐dextran. This showed that the tight junctions already form a functional barrier in early development by preventing the paracellular movement of the tracer. Intracellular staining shows that there may be a transcellular route for these molecules through the epithelial cells from blood to CSF. Apart from lacking a glycogen‐rich stage, cellular changes in the developing opossum plexus seem to be similar to those in other species, demonstrating that this is a good model for studies of mammalian choroid plexus development. J. Comp. Neurol. 460:451–464, 2003. © 2003 Wiley‐Liss, Inc.
Expression of Prox1 defines regions of the avian otocyst that give rise to sensory or neural cells
Authors: Stone Jennifer S. , Shang Jia‐Lin , Tomarev Stanislav
Published: April 2003

The simple primordium of the inner ear (otocyst) differentiates into many cell types, including sensory neurons and hair cells. We examined expression of the divergent homeobox transcription factor, cProx1, during otocyst development in chickens. Nuclear cProx1 protein is not evident in the otic placode but emerges in the otic cup by stage 12. At stage 16, cProx1‐positive nuclei are scattered continuously throughout the neuroepithelium, from anteroventral to posteromedial. These labeled cells are neural precursors; they express βIII‐tubulin and migrate to the cochleovestibular ganglion between stages 13 and 21. By stage 18, two areas develop a dense pattern of cProx1 expression in which every nucleus is labeled. These areas emerge at the anterior and posterior extremes of the band of scattered cProx1 expression and express the sensory markers cSerrate1 and Cath1 by stage 23. Four discrete patches of dense cProx1 expression appear by stage 23 that correspond to the future superior crista, lateral crista, saccular macula, and posterior crista, as confirmed by immunolabeling for hair cell antigen (HCA) by stage 29. The remaining sensory epithelia display a dense pattern of cProx1 expression and label for HCA by stage 29. In the basilar papilla, nuclear cProx1 expression is down‐regulated in most hair cells by stage 37 and in many supporting cells by stage 40. Our findings show that regions of the otocyst that give rise to neurons or hair cells are distinguished by their relative density of cProx1‐positive nuclei, and suggest a role for cProx1 in the genesis of these cell types. J. Comp. Neurol. 460:487–502, 2003. Published 2003 Wiley‐Liss, Inc.
Fos expression by glutamatergic neurons of the solitary tract nucleus after phenylephrine‐induced hypertension in rats
Authors: Weston Matthew , Wang Hong , Stornetta Ruth L. , Sevigny Charles P. , Guyenet Patrice G.
Published: April 2003

The baroreflex pathway might include a glutamatergic connection between the nucleus of the solitary tract (NTS) and a segment of the ventrolateral medulla (VLM) called the caudal ventrolateral medulla. The main goal of this study was to seek direct evidence for such a connection. Awake rats were subjected to phenylephrine‐ (PE‐) induced hypertension (N=5) or received saline (N=5). Neuronal activation was gauged by the presence of Fos‐immunoreactive (Fos‐ir) nuclei. Fos‐ir neurons that contained vesicular glutamate transporter 2 mRNA (glutamatergic neurons) or glutamic acid decarboxylase mRNA (GABAergic neurons) were mapped throughout the medulla oblongata. Saline‐treated rats had very few Fos‐ir neurons. In PE‐treated rats, Fos‐ir neurons were detected in both NTS and VLM. In NTS, 72% of Fos‐ir neurons were glutamatergic and 26% were GABAergic. In the VLM, 41% of Fos‐ir neurons were glutamatergic and 56% were GABAergic. In VLM, Fos‐ir glutamatergic neurons were evenly distributed and were often catecholaminergic, whereas Fos‐ir GABAergic cells were clustered around Bregma −13.0 mm. This region of the VLM was injected with Fluoro‐Gold (FG) in eight rats, four of which received PE and the rest saline. Fos‐ir NTS neurons retrogradely labeled with FG were detected only in PE‐treated rats. These cells were exclusively glutamatergic and were concentrated within the NTS subnuclei that receive the densest inputs from arterial baroreceptors. In conclusion, PE, presumably via baroreceptor stimulation, induces Fos in glutamatergic and GABAergic neurons in both NTS and VLM. At least 29% of the Fos‐ir glutamatergic neurons of NTS project to the vicinity of the VLM GABAergic interneurons that are presumed to mediate the sympathetic baroreflex. J. Comp. Neurol. 460:525–541, 2003. © 2003 Wiley‐Liss, Inc.
Aging alters dendritic morphology, input resistance, and inhibitory signaling in dentate granule cells of the rhesus monkey
Authors: Luebke Jennifer I. , Rosene Douglas L.
Published: April 2003

The neural substrates of age‐related hippocampal dysfunction in primates are poorly understood. This issue was addressed with combined intracellular biocytin filling and whole‐cell patch clamp recordings of intrinsic membrane properties and inhibitory postsynaptic currents (IPSCs) in dentate granule cells in in vitro slices prepared from behaviorally characterized young (<11 years old) and aged (>24 years old) rhesus monkeys. Six of nine aged monkeys were significantly impaired in performance on the hippocampally mediated delayed nonmatch to sample (DNMS) task at a 2‐minute delay. Morphometric analyses showed that cells from aged monkeys had significantly reduced vertical dendritic extents and distal dendritic branching but increased proximal dendritic branching. Intrinsic membrane and action potential properties did not differ between cells from young and aged monkeys with the exception of a small but significant increase in input resistance with age. The frequency, amplitude, and rise time of γ‐aminobutyric acid (GABA)A receptor‐mediated miniature IPSCs were not significantly different in cells from young vs. aged monkeys. However, the miniature IPSC decay time constant and the benzodiazepine potentiation of this decay time constant were both significantly increased in cells from aged monkeys. These differences in the properties of dentate granule cells correlated positively with age but not specifically with impairment on the DNMS 2‐minute delay task. Nevertheless, these changes in dendritic morphology, input resistance, and inhibitory signaling properties may be part of a constellation of subtle functional changes contributing to age‐associated cognitive impairment. J. Comp. Neurol. 460:573–584, 2003. © 2003 Wiley‐Liss, Inc.
Rabbit forebrain cholinergic system: Morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus
Authors: Varga Csaba , Härtig Wolfgang , Grosche Jens , Keijser Jan , Luiten Paul G.M. , Seeger Johannes , Brauer Kurt , Harkany Tibor
Published: April 2003

Although the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output pathways are still awaited. Therefore, we performed quantitative choline acetyltransferase (ChAT) immunocytochemistry to localize major cholinergic nuclei and to determine the number of respective cholinergic neurons in the rabbit forebrain. The density of ChAT‐immunoreactive terminals in layer V of distinct neocortical territories and in hippocampal subfields was also measured. Another cholinergic marker, the low‐affinity neurotrophin receptor (p75NTR), was also employed to identify subsets of cholinergic neurons. Double‐immunofluorescence labeling of ChAT and p75NTR, calbindin D‐28k (CB), parvalbumin, calretinin, neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase, or substance P was used to elucidate the neuroanatomical borders of cholinergic nuclei and to analyze the neurochemical complexity of cholinergic cell populations. Cholinergic projection neurons with heterogeneous densities were found in the medial septum, vertical and horizontal diagonal bands of Broca, ventral pallidum, and magnocellular nucleus basalis (MBN)/substantia innominata (SI) complex; cholinergic interneurons were observed in the caudate nucleus, putamen, accumbens nucleus, and olfactory tubercule, whereas the globus pallidus was devoid of cholinergic nerve cells. Cholinergic interneurons were frequently present in the hippocampus and to a lesser extent in cerebral cortex. Cholinergic projection neurons, except those localized in SI, abundantly expressed p75NTR, and a subset of cholinergic neurons in posterior MBN was immunoreactive for CB and nNOS. A strict laminar distribution pattern of cholinergic terminals was recorded both in the cerebral cortex and in CA1–CA3 and dentate gyrus of the hippocampus. In summary, the structural organization and chemoarchitecture of rabbit basal forebrain may be considered as a transition between that of rodents and that of primates. J. Comp. Neurol. 460:597–611, 2003. © 2003 Wiley‐Liss, Inc.
Short‐term and long‐term survival of new neurons in the rat dentate gyrus
Authors: Dayer Alexandre G. , Ford Abigail A. , Cleaver Kathryn M. , Yassaee Mina , Cameron Heather A.
Published: April 2003

New neurons continue to be generated in the dentate gyrus throughout adulthood. Previous studies have shown that a significant proportion of new granule cells labeled with the thymidine analogue bromodeoxyuridine (BrdU) are lost from the adult dentate gyrus within 2 weeks. How long this loss continues and the extent to which it represents cell death, as opposed to dilution of label, is unclear. To address these questions, adult rats were injected with BrdU, and BrdU labeling in the dentate gyrus was compared at several survival time points. Double labeling with BrdU and the cell cycle marker Ki‐67 showed that BrdU is detectable for up to 4 days in some cells that continue to divide, indicating that any decrease in the number of BrdU‐labeled cells after 4 days is likely to reflect cell death rather than BrdU dilution. Death of new cells in the granule cell layer occurred at a steady rate between 6 and 28 days after labeling, resulting in loss of 50% of BrdU‐labeled cells over this 22‐day period. New granule cells that survived this first month lived for at least 5 additional months. In contrast, 26% of the granule cells labeled with BrdU at the peak of dentate gyrus development on postnatal day (P) 6 died between 1 and 6 months after labeling. These findings suggest that granule cells born during adulthood that become integrated into circuits and survive to maturity are very stable and may permanently replace granule cells born during development. J. Comp. Neurol. 460:563–572, 2003. Published 2003 Wiley‐Liss, Inc.
Upregulation of calretinin immunostaining in the ferret inferior colliculus after cochlear ablation
Authors: Fuentes‐Santamaria Verónica , Alvarado Juan Carlos , Brunso‐Bechtold Judy K. , Henkel Craig K.
Published: April 2003

In many systems, including ascending auditory pathways, calcium‐binding proteins are markers of specific neuronal circuits. Previous studies suggest that calretinin immunostaining may be a specific marker for circuits in the inferior colliculus (IC) that code timing information. We undertook experiments to determine the changes in calretinin immunostaining in the IC that take place in response to cochlear ablation. Cochlear ablation was performed unilaterally in ferrets just after hearing onset. Animals survived for 2–3 months after ablation and brains were then processed for calretinin immunocytochemistry. The mean optical density and stained area of the calretinin immunopositive plexus in the IC were determined for five coronal sections through the right and left IC. In controls (n = 3), measurements of these parameters in the central nucleus of the IC showed symmetry between the two sides. In experimental animals (n = 8) the calretinin immunopositive plexus contralateral to the cochlear ablation was denser and larger than that in either the ipsilateral IC or in the IC of control animals. The calretinin plexus in the ipsilateral IC was slightly less dense and smaller than in controls but the differences did not reach statistical significance. IC volume measurements and synaptophysin immunostaining analysis in the central nucleus of the IC revealed no statistical differences between ablated and control animals or between the two sides in ablated animals. The significant increase in both mean optical density and immunostained area of the calretinin plexus in the IC contralateral to the cochlear ablation may reflect an upregulation in calretinin expression in the nuclei that contribute to this plexus. J. Comp. Neurol. 460:585–596, 2003. © 2003 Wiley‐Liss, Inc.
Sexual differentiation of projections from the principal nucleus of the bed nuclei of the stria terminalis
Authors: Gu Guibao , Cornea Anda , Simerly Richard B.
Published: April 2003

The principal nucleus of the bed nuclei of the stria terminalis (BSTp) is sexually dimorphic and participates in several aspects of reproduction. A detailed analysis of its projections revealed that the BSTp provides major inputs to forebrain regions that are sexually dimorphic and contain high densities of neurons that express receptors for sex steroid hormones in a pattern that is remarkably similar to that of the medial amygdaloid nucleus. The BSTp sends its strongest outputs to the periventricular zone of the hypothalamus and innervates structures thought to play important roles in regulating hormone secretion from the anterior pituitary, but it also provides strong inputs to the medial preoptic and ventromedial nuclei of the hypothalamus. The BSTp also sends a strong return projection to the medial nucleus of the amygdala. The projections of the BSTp appear to be more robust in males with striking sex differences observed in most, but not all, major terminal fields. Moreover, various terminal fields appeared to differ in their developmental sensitivity to manipulation of circulating levels of sex steroids during the neonatal period. Thus, the organization of projections from the BSTp suggests that it plays a particularly important role in regulating neuroendocrine function and that neurons in this nucleus may relay olfactory information to the hypothalamus differently in male and female rats. Furthermore, the differential action of sex steroids on the density of afferents from the BSTp in various regions indicates that these hormones exert a target‐specific influence on the development of BSTp projections. J. Comp. Neurol. 460:542–562, 2003. © 2003 Wiley‐Liss, Inc.
Mercury minimization measures to meet total maximum daily load requirements
Authors: Pickard Brian C.
Published: April 2003

Mercury is a naturally occurring element that bioaccumulates due to its tendency to associate with organic
matter. Thus methylmercury, the organic (and most toxic) mercury form, will bioaccumulate up the food
chain, with the largest aquatic concentrations found in predatory fish. Five segments of the lower Savannah River
were listed on the state of Georgia's 2000 Section 303(d) list of impaired waters because mercury
in certain species of fish tissue exceeded fish consumption (the primary human route of exposure)
guidelines. Consequently, EPA developed a Total Maximum Daily Load (TMDL) for total mercury for the
middle/lower Savannah River. An Army installation, located in the affected watershed and identified as a
significant mercury contributor, was allowed a 7.43E‐06 kg/yr wasteload allocation (WLA) of
discharged mercury. In lieu of end‐of‐pipe sampling, the installation chose development and
implementation of a mercury minimization plan (MMP) for TMDL compliance. This article describes the
methodology used for MMP development and summarizes the policies, procedures, and guidelines used to reduce
and/or eliminate mercury‐containing discharges into the wastewater collection system. © 2003
Wiley Periodicals, Inc.
The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer
Authors: Hansen Lasse Tengbjerg , Lundin Cecilia , Spang‐Thomsen Mogens , Petersen Lone Nørgård , Helleday Thomas
Published: April 2003

Etoposide (VP16) is a potent inducer of DNA double‐strand breaks (DSBs) and is efficiently used in small cell lung cancer (SCLC) therapy. However, acquired VP16 resistance remains an important barrier to effective treatment. To understand the underlying mechanisms for VP16 resistance in SCLC, we investigated DSB repair and cellular VP16 sensitivity of SCLC cells. VP16 sensitivity and RAD51, DNA‐PKcs, topoisomerase IIα and P‐glycoprotein protein levels were determined in 17 SCLC cell lines. In order to unravel the role of RAD51 in VP16 resistance, we cloned the human RAD51 gene, transfected SCLC cells with RAD51 sense or antisense constructs and measured the VP16 resistance. Finally, we measured VP16‐induced DSBs in the 17 SCLC cell lines. Two cell lines exhibited a multidrug‐resistant phenotype. In the other SCLC cell lines, the cellular VP16 resistance was positively correlated with the RAD51 protein level. In addition, downregulation or overexpression of the RAD51 gene altered the VP16 sensitivity. Furthermore, the levels of the RAD51 and DNA‐PKcs proteins were related to VP16‐induced DSBs. The results suggest that repair of VP16‐induced DSBs is mediated through both RAD51‐dependent homologous recombination and DNA‐PKcs‐dependent nonhomologous end‐joining and may be a determinant of the variation in clinical treatment effect observed in human SCLC tumors of identical histologic subtype. Finally, we propose RAD51 as a potential target to improve VP16 efficacy and predict tumor resistance in the treatment of SCLC patients. © 2003 Wiley‐Liss, Inc.
Tumor‐localization by adoptively transferred, interleukin‐2‐activated NK cells leads to destruction of well‐established lung metastases
Authors: Yang Qin , Hokland Marianne E. , Bryant John L. , Zhang Yuquing , Nannmark Ulf , Watkins Simon C. , Goldfarb Ronald H. , Herberman Ronald B. , Basse Per H.
Published: April 2003

We have shown previously that i.v. injection of interleukin‐2‐(IL‐2) activated natural killer (A‐NK) cells together with IL‐2 leads to a substantial localization of the A‐NK cells into most, but not all, well‐established B16 lung metastases in C57BL/6 mice within 12–24 hr. We demonstrate that the morphology of the lung metastases, (loose or more compact in appearance), and their location in the lungs (on the surface or deep in the lung parenchyma) are closely tied to the infiltration‐permissiveness of the metastases as well as their sensitivity to treatment with A‐NK cells. Although more than 1,100 A‐NK cells/mm2 were found in deep metastases with a “loose” morphology (D‐L), only 534, 90 and 89 cells/mm2 were found in surface‐loose (S‐L), surface‐compact (S‐C) and deep‐compact (D‐C) metastases, respectively. The best infiltrated metastases responded best to the A‐NK cell therapy. Thus, metastases of the D‐L phenotype became reduced by 65–90% after treatment with 2 × 106 A‐NK cells and IL‐2 (120,000 IU Peg‐IL‐2 every 12 hr for 3 days) compared to similar lesions in animals treated with PEG‐IL‐2 alone. In contrast, poorly infiltrated metastases, that is lesions of the compact phenotype (D‐C and S‐C) as well as loose metastases on the lung surface (S‐L), did not react significantly to this treatment. We conclude that adoptively transferred A‐NK cells are able to eliminate even well‐established metastases. The existence of metastases that are resistant to infiltration by the transferred effector cells at time of treatment might reduce the efficacy of cell‐based immuno‐therapeutic ventures. © 2003 Wiley‐Liss, Inc.
Decomposition of the complete graph plus a 1‐factor into cycles of equal length
Authors: Šajna Mateja
Published: April 2003

We determine the necessary and sufficient conditions for the existence of a decomposition of the complete graph of even order with a 1‐factor added into cycles of equal length. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 170–207, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10019
Homogeneous and ultrahomogeneous Steiner systems
Authors: Devillers Alice
Published: April 2003

A Steiner system (or t — (v, k, 1) design) S is said to be homogeneous if, whenever the substructures induced on two finite subsets S1 and S2 of S are isomorphic, there is at least one automorphism of S mapping S1 onto S2, and is said to be ultrahomogeneous if each isomorphism between the substructures induced on two finite subsets of S can be extended to an automorphism of S. We give a complete classification of all homogeneous and ultrahomogeneous Steiner systems. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 153–161, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10034
Largest minimal blocking sets in PG(2,8)
Authors: Barát J. , Innamorati S.
Published: April 2003

Bruen and Thas proved that the size of a large minimal blocking set is bounded by$q \cdot {\sqrt{q}} + 1$. Hence, ifq = 8, then the maximal possible size is 23. Since 8 is not a square, it was conjectured that a minimal blocking 23‐set does not exist in PG(2,8). We show that this is not the case, and construct such a set. We prove that this is combinatorially unique. We also complete the spectrum problem of minimal blocking sets for PG(2,8) by showing a minimal blocking 22‐set. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 162–169, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10035
The additive and interactive effects of parenting and children's personality on externalizing behaviour
Authors: Prinzie P. , Onghena P. , Hellinckx W. , Grietens H. , Ghesquière P. , Colpin H.
Published: April 2003

Parenting practices have been previously linked to childhood externalizing behaviour. However, little attention has been given to the potential effect of individual personality differences among children on this relation. The current study assesses the additive effects of children's personality characteristics and explores the moderating effects of children's personality on relations between parenting practices and childhood externalizing behaviour using a proportional stratified sample of 599 nonclinical elementary‐school‐aged children. Multiple regression analyses reveal that in the mother data as well as in the father data, dysfunctional parenting and the children's personality characteristics Benevolence, Conscientiousness, and Extraversion were directly related to outcomes consistent with an additive model of their effects. Significant interactions indicate that children with low scores on Benevolence who were exposed to overreactive discipline practices exhibited higher levels of externalizing behaviour. Children characterized by low scores on Conscientiousness who were exposed to coercive parenting behaviour showed elevated levels of externalizing behaviour. These results suggest that integrating children's personality characteristics within parenting models can improve the understanding of the aetiology of childhood externalizing problem behaviour. The implications of such integrations for intervention are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Personality and approaches to learning as predictors of academic achievement
Authors: Diseth Åge
Published: April 2003

The relationship between personality, approaches to learning, and academic achievement was investigated. Two different undergraduate student samples, totalling 310 students, participated in the study. Results showed the expected significant correlations between the personality factors of openness, neuroticism, and conscientiousness, on the one hand, and deep, surface, and strategic approaches to learning, on the other. A significant negative correlation between surface approach and achievement was observed in sample 1. In sample 2, achievement was positively correlated with neuroticism, openness, and deep approach, and negatively correlated with agreeableness. Path analysis showed that each approach to learning was predicted by multiple personality traits, and that academic achievement was predicted by approaches to learning. A separate analysis showed that the relationship between openness and achievement was mediated by a deep approach to learning. Copyright © 2002 John Wiley & Sons, Ltd.
Cognitive style: a psycholexically‐derived personality‐centred model
Authors: Roodenburg John
Published: April 2003

Cognitive style suffers from a confusing multitude of conceptualizations, and dominance by information‐processing type measures. This study sought to elucidate a comprehensive and universal set of personality‐centred cognitive style constructs. A grounded approach based on the psycholexical hypothesis (effective in personality modelling) was adapted, explicating cognitive styles as evident in late adolescents. Approximately 700 Australian secondary teachers generated a lexicon of 1040 style adjectives, which were consolidated into 99 key words. 596 teachers rated 1192 senior secondary students against these. After removing acquiescence and a ubiquitous good–bad‐ability factor, optimum structure appears to be a spherex abridgeable as three circumplexes, reported across six factor pure and 24 blended facets. Copyright © 2003 John Wiley & Sons, Ltd.
Personality variable differences between disease clusters
Authors: Matthews G. , Yousfi S. , Schmidt‐Rathjens C. , Amelang M.
Published: April 2003

Previous studies of personality and health have focused mainly on the influence of psychological factors on single diseases such as cancer and coronary heart disease (CHD), thereby neglecting the problem of comorbidity (i.e. the combination of different diseases). The main focus of the present study was the discrimination between single‐ and multiple‐disease conditions on the basis of personality traits. An extensive battery of personality scales implicated in health was administered to a sample of n=5133 individuals of both genders between the ages of 40 and 65. Subjects also reported their health or illness status. A factor analysis of the personality scales yielded five dimensions clearly interpretable as “Emotional Lability”, “Type A Behaviour”, “Behavioural Control”, “Locus of Control over Diseases”, and “Psychoticism”. Hierarchical cluster analyses of the subsample of participants who reported suffering from more than one disease led to eight clusters representing individuals with different combinations of diseases. Generally, there were very few significant differences between healthy and single‐disease participants with regard to personality. However, mean factor scores calculated for “Emotional Lability” were higher across the multiple‐disease groups than in the healthy and single‐disease groups. No other personality factor showed this trend. In general the results reported here show the important role negative affectivity (e.g. Emotional Lability, Neuroticism, Depression) plays in differentiating between single and multiple diseases. Copyright © 2003 John Wiley & Sons, Ltd.
Metal chelate polymers derived from tetraacetylethane
Authors: Charles Robert G.
Published: April 2003

Polymeric materials have been prepared by the reaction of the divalent Cu, Ni, Co, Zn, Cd, and Mg cations with the dipotassium salt of tetraacetylethane in methanol–water solutions. The polymers appear to be of low molecular weight and generally contain potassium in the endgroups. The insoluble, infusible, materials decompose on heating in the absence of air to give, among other products, H2, 3,4‐diacetyl‐2,5‐dimethylfuran, and the free metal or metal oxide. The order of decreasing heat stability is Mg > Ni > Co > tetraacetylethane > Cu > Zn > Cd. The Cd chelate polymer decomposes appreciably at 225°C., while the Mg polymer, heated under the same conditions, begins to decompose at about 350°C.
Some aspects of the production and study of semiconducting polymeric materials
Authors: Topchiev A. V.
Published: April 2003

The paper deals with theoretical and experimental data on polymeric products with semiconducting properties. The data show the possibility of producing, on the basis of polymers, particularly polyacrylonitrile, substances characterized by high electroconductivity and exponential dependence of the latter on temperature. Possible changes in electrophysical properties of the materials are discussed. A quasimetallic model of a polymeric semiconductor is described.
Polymerization of allene by organometallic initiation
Authors: Baker William P.
Published: April 2003

Allene has been polymerized to a high molecular weight by several transition metal salts reduced by aluminum triisobutyl. The polymer contained three types of unsaturation: vinylidene, vinyl, and cis; no trans unsaturation was found. A hypothesized mechanism accounted for these facts by two competitive rates: reaction of a linear intermediate with monomer to form again the linear intermediate plus one vinylidene unit, and isomerization of the linear intermediate to a cyclic intermediate which ultimately yielded one vinylidene and one vinyl or cis unit after reaction with monomer. Thus, the ratio of the two rates was controlled by the concentration of allene. The suggested mechanism proved to predict accurately the effect of the conditions of polymerization upon the structures of the resulting polymers. The nature of the transition metal also proved of importance in determining the path of polymerization as did temperature, solvent, degree of agitation, and copolymerization. Polyallene was found to exist in three crystalline forms as well as an amorphous form.
Dynamic properties of homo‐ and copolymers of 4‐methyl‐1‐pentene
Authors: Hewett W. A. , Weir F. E.
Published: April 2003

Dynamic measurements of homo‐ and copolymers of 4‐methyl‐1‐pentene have been made with a self‐damped torsion pendulum. It has been shown that one can calculate the glass transition temperature of these copolymers by means of an equation suggested by T. Fox. It has also been shown that there is a danger in correlating per cent insolubles with crystallinity in a new polymer system without considering molecular weight.
Polymerization induced by ionizing radiation at low temperatures. III. The effect of electron density on the polymerization of substituted styrenes
Authors: Hsia Chen Catherine S.
Published: April 2003

The solution polymerization in methylene chloride of different methyl‐, methoxy‐and chloro‐substituted styrenes has been studied both at a low temperature (−65°C.) and at a higher temperature (+25°C.). The rates of the m‐ and p‐substituted monomers are correlated with the Hammett linear free‐energy relationship at both temperatures and the σ+ constants of Brown and Okamoto. The hypothesis that at low temperatures the polymerization mechanism is cationic and at higher temperatures the mechanism is free‐radical is further supported by a negative value for p at −65°C. and nearly zero value for p at 25°C. obtained from the Hammett plots at the respective temperatures. Solid‐state polymerizations of undiluted p‐methylstyrene, o‐methylstyrene, and α‐methylstyrene also have been investigated. It has been found that the termination is unimolecular for o‐methylstyrene and p‐methylstyrene. The rates for α‐methylstyrene at −80°C. in the solid state are extremely slow. By comparing the results obtained for the solid‐state and for the solution polymerizations of p‐methylstyrene, o‐methylstyrene, and α‐methylstyrene, the hypothesis that the crystal structure plays an important role in determining the rate of solid‐phase polymerization and its mechanism is further substantiated by the differences observed. The polymerization of undiluted p‐methylstyrene at 0°C. and at −15°C. in the liquid phase has been undertaken. It has been found that at both temperatures the polymerization is ionic in nature, as evidenced by the dose rate dependences and by the negative activation energy. The polymerization of p‐methoxystyrene in methylene chloride (∼3.5 moles/1.) has been undertaken from −80°C. to 25°C., covering both solid and liquid phases. In the liquid phase a change of mechanism with change of temperature is again observed. In the solid phase the polymerization is probably of a different nature and is not well understood.
Copolymerization of styrene and styrene derivative with an aluminum alkyl‐titanium trichloride catalyst
Authors: Overberger C. G. , Nozakura S.
Published: April 2003

Copolymerizations of styrene with p‐tert‐butyl‐, o‐methyl‐, 2,6‐dimethyl‐, and p‐fluorostyrene were carried out with an alkyl aluminum—titanium trichloride catalyst. Overall composition of the product indicated that substituted styrenes were less reactive than expected for a conventional free‐radical or ionic mechanism in solution. This fact led to a suggestion of a special steric interaction of the penultimate monomeric unit in the propagation step for this heterogeneous system. A styrene–p‐tert‐butylstyrene copolymer was fractionated, showing that it was composed of two or more copolymers of different compositions. The similar situation holds for the other cases except for 2,6‐dimethylstyrene, which did not homopolymerize and did not copolymerize. The result was explained by the assumption of either multiactivity of the catalyst due to differences in site activity or a diffusion‐controlled process.