bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal phenotype and localization of spinal cord V1 derived interneurons
Authors: Alvarez Francisco J. , Jonas Philip C. , Sapir Tamar , Hartley Robert , Berrocal Maria C. , Geiman Eric J. , Todd Andrew J. , Goulding Martyn
Published: October 2005

Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little is known, however, about their adult phenotypes. Therefore, we characterized the location, neurotransmitter phenotype, calcium‐buffering protein expression, and axon distributions of V1‐derived neurons in the adult mouse spinal cord. In the mature (P20 and older) spinal cord, most V1‐derived neurons are located in lateral LVII and in LIX, few in medial LVII, and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium‐buffering protein expression, two groups (1 and 4) correspond with V1‐derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1‐derived neurons. V1‐derived Group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons. The most ventral neurons in this group receive convergent calbindin‐IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1‐derived neurons. Adult V1‐interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1 axons do not cross the midline. V1‐derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons, and other unidentified proprioceptive interneurons. J. Comp. Neurol. 493:177–192, 2005. © 2005 Wiley‐Liss, Inc.
Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach
Authors: Beckett Elizabeth A.H. , Takeda Yukari , Yanase Haruko , Sanders Kenton M. , Ward Sean M.
Published: October 2005

Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC‐IM) in the stomach and colon and ICC in the deep muscular plexus (ICC‐DMP) of the small intestine. In the absence of ICC‐IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC‐IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse‐associated proteins between nerve terminals and ICC‐IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP‐25 were detected. Synaptotagmin and SNAP‐25‐immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC‐IM but not smooth muscle. W/WV mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC‐IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP‐25 were detected in W/WV tissues. In the absence of ICC‐IM, synaptotagmin and SNAP‐25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT‐PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD‐93 and PSD‐95 in the stomach and expression levels of PSD‐93 and PSD‐95 were reduced in W/WV mutants. These data support the existence of synaptic specializations between enteric nerves and ICC‐IM in gastric tissues. In the absence of ICC‐IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals. J. Comp. Neurol. 493:193–206, 2005. © 2005 Wiley‐Liss, Inc.
Dual, multilayered somatosensory maps formed by antennal tactile and contact chemosensory afferents in an insect brain
Authors: Nishino Hiroshi , Nishikawa Michiko , Yokohari Fumio , Mizunami Makoto
Published: October 2005

The antennae of most insects move actively and detect the physical and chemical composition of objects encountered by using their associated tactile sensors. Positional information is required for these sensory modalities to interpret the physical environment. Although we have a good understanding of antennal olfactory pathways, little is known about the destinations of antennal mechanosensory and contact chemosensory (gustatory) receptor neurons in the central nervous system. The cockroach Periplaneta is equipped with a pair of long, thin antennae, which are covered in bristles. The distal portions of each antenna possess about 6,500 bimodal bristles that house one tactile sensory and one to four contact chemosensory neurons. In this study, we investigated the morphologies of bimodal bristle receptor afferents by staining individual or populations of bristles. Unlike olfactory afferents, which project exclusively into the glomeruli in the ventral region of the deutocerebrum, both the presumptive mechanosensory and the contact chemosensory afferents projected into the posterior dorsal region of the deutocerebrum and the anterior region of the subesophageal ganglion. Each afferent showed multilayered segmentation and spatial occupation reflecting its three‐dimensional position in the periphery. Presumptive contact chemosensory afferents, characterized by their thin axons and unique branching pattern, occupied more medioventral positions compared with the presumptive tactile afferents. Furthermore, projection fields of presumptive contact chemosensory afferents from single sensilla tended to be segregated from each other. These observations suggest that touch and taste positional information from the antenna is precisely represented in primary centers in a modality‐specific manner. J. Comp. Neurol. 493:291–308, 2005. © 2005 Wiley‐Liss, Inc.
Morphological impairments in retinal neurons of the scotopic visual pathway in a monkey model of Parkinson's disease
Authors: Cuenca Nicolás , Herrero María‐Trinidad , Angulo Antonia , de Juan Emilio , Martínez‐Navarrete Gema C. , López Salvador , Barcia Carlos , Martín‐Nieto José
Published: October 2005

Physiological abnormalities resulting from death of dopaminergic neurons of the central nervous system in Parkinson's disease also extend to the retina, resulting in impaired visual functions. In both parkinsonian patients and animal models, low levels of dopamine and loss of dopaminergic cells in the retina have been reported. However, the morphology and connectivity of their postsynaptic neurons, the amacrine cells, have not been analyzed. Here we report, with macaques chronically treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) as a model of Parkinson's disease, that morphological impairments in dopaminergic retinal neurons and their plexus in the inner retina are accompanied by an immunoreactivity decrease in γ‐aminobutyric acidergic and glycinergic amacrine cells. Especially deteriorated were AII amacrine cells, the main neuronal subtype postsynaptic to dopaminergic cells, which exhibited a marked loss of lobular appendages and dendritic processes. Concomitantly, electrical synapses among AII cells, as well as chemical synapses between these and rod bipolar cells, were highly deteriorated in parkinsonian monkeys. These results highlight that the scotopic visual pathway is severely impaired in the parkinsonian condition and provide a morphological basis for a number of abnormalities found in electrophysiological and psychophysical trials in Parkinson's disease patients and animal models. J. Comp. Neurol. 493:261–273, 2005. © 2005 Wiley‐Liss, Inc.
Comparison of α2 nicotinic acetylcholine receptor subunit mRNA expression in the central nervous system of rats and mice
Authors: Ishii Katsuyoshi , Wong Jamie K. , Sumikawa Katumi
Published: October 2005

The nicotinic acetylcholine receptor (nAChR) α2 subunit was the first neuronal nAChR to be cloned. However, data for the distribution of α2 mRNA in the rodent exists in only a few studies. Therefore, we investigated the expression of α2 mRNA in the rat and mouse central nervous systems using nonradioactive in situ hybridization histochemistry. We detected strong hybridization signals in cell bodies located in the internal plexiform layer of the olfactory bulb, the interpeduncular nucleus of the midbrain, the ventral and dorsal tegmental nuclei, the median raphe nucleus of the pons, the ventral part of the medullary reticular nucleus, the ventral horn in the spinal cord of both rats and mice, and in a few Purkinje cells of rats, but not of mice. Cells that moderately express α2 mRNA were localized to the cerebral cortex layers V and VI, the subiculum, the oriens layer of CA1, the medial septum, the diagonal band complex, the substantia innominata, and the amygdala of both animals. They were also located in a few midbrain nuclei of rats, whereas in mice they were either few or absent in these areas. However, in the upper medulla oblongata α2 mRNA was expressed in several large neurons of the gigantocellular reticular nucleus and the raphe magnus nucleus of mice, but not of rats. The data obtained show that a similar pattern of α2 mRNA expression exists in both rats and mice, with the exception of a few regions, and provide the basis for cellular level analysis. J. Comp. Neurol. 493:241–260, 2005. © 2005 Wiley‐Liss, Inc.
Neuronal architecture of the mosquito deutocerebrum
Authors: Ignell Rickard , Dekker Teun , Ghaninia Majid , Hansson Bill S.
Published: October 2005

Mosquito behavior is heavily dependent on olfactory and mechanosensory cues, which are detected by receptor neurons on the antenna and on the palps. Recent progress in mosquito sensory genomics highlights the need for an up‐to‐date understanding of the neural architecture of the mosquito brain. Here we present a detailed description of the neural structure of the primary target of the majority of these neurons, the deutocerebrum, in the African malaria (Anopheles gambiae) and yellow fever (Aedes aegypti) mosquitoes. Special focus is made on the olfactory system, the antennal lobe (AL), where we present high‐resolution three‐dimensional models of the ALs of male and female Ae. aegypti. These models reveal a sexual dimorphism in the number of glomeruli, 49 and 50 glomeruli in male and female mosquitoes, respectively, and in the size of several of the identified glomeruli. The fine structure of receptor neuron terminations in the AL and the rest of the deutocerebrum is described, as are the arborizations of intrinsic deutocerebral neurons and neurons providing output to higher brain areas. In the AL a specific and very large center receiving input from the mechanosensory Johnston's organ is revealed as a multilobed structure receiving peripheral input according to a somatotopic pattern. Within the antennal nerve a specific neuropil containing early, bouton‐like ramifications of receptor neurons is described. Within the glomerular array of the AL, neurons providing a possible feedback circuit to antennal receptor neurons are shown. With these results we provide a new resolution in mosquito deutocerebral architecture. J. Comp. Neurol. 493:207–240, 2005. © 2005 Wiley‐Liss, Inc.
Buried alive: How osteoblasts become osteocytes
Authors: Franz‐Odendaal Tamara A. , Hall Brian K. , Witten P. Eckhard
Published: October 2005

During osteogenesis, osteoblasts lay down osteoid and transform into osteocytes embedded in mineralized bone matrix. Despite the fact that osteocytes are the most abundant cellular component of bone, little is known about the process of osteoblast‐to‐osteocyte transformation. What is known is that osteoblasts undergo a number of changes during this transformation, yet retain their connections to preosteoblasts and osteocytes. This review explores the osteoblast‐to‐osteocyte transformation during intramembranous ossification from both morphological and molecular perspectives. We investigate how these data support five schemes that describe how an osteoblast could become entrapped in the bone matrix (in mammals) and suggest one of the five scenarios that best fits as a model. Those osteoblasts on the bone surface that are destined for burial and destined to become osteocytes slow down matrix production compared to neighbouring osteoblasts, which continue to produce bone matrix. That is, cells that continue to produce matrix actively bury cells producing less or no new bone matrix (passive burial). We summarize which morphological and molecular changes could be used as characters (or markers) to follow the transformation process. Developmental Dynamics 235:176–190, 2006. © 2005 Wiley‐Liss, Inc.
The 5′ zebrafish scl promoter targets transcription to the brain, spinal cord, and hematopoietic and endothelial progenitors
Authors: Jin Hao , Xu Jin , Qian Feng , Du Linsen , Tan Chee Yong , Lin Zhixin , Peng Jinrong , Wen Zilong
Published: October 2005

The stem cell leukemia (SCL) gene encodes a basic helix–loop–helix transcription factor and is essential for embryonic angiogenesis, hematopoietic stem cell specification, and erythrocyte maturation. Here, we report the isolation and characterization of the zebrafish scl promoter. We show that a 5‐kilobase (kb) genomic fragment immediately upstream of the translation start site is capable of targeting the enhanced green fluorescence protein (EGFP) expression to the anterior and posterior lateral mesoderm where the endogenous scl normally expresses. Detailed analysis of the stable transgenic fish reveals that this 5‐kb upstream sequence is sufficient to direct the EGFP transcription to the brain, spinal cord, and hematopoietic–endothelial progenitors, possibly the hemangioblast, but not primitive erythrocyte, suggesting that the zebrafish scl transcription in hematopoietic–endothelial progenitors and erythrocyte is regulated by distinct cis element(s). Our study has defined the cis regulatory element(s) for zebrafish scl expression in the brain, spinal cord, and hematopoietic–endothelial progenitors and established a valuable transgenic line Tg(5′5kbscl:EGFP) for studying hematopoietic lineage development. Developmental Dynamics 235:60–67, 2006. © 2005 Wiley‐Liss, Inc.
PINCH‐1 expression during early avian embryogenesis: Implications for neural crest and heart development
Authors: Martinsen Brad J. , Neumann Ann N. , Frasier Allison J. , Baker Clare V.H. , Krull Catherine E. , Lohr Jamie L.
Published: October 2005

The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent OFT septation are critical events during vertebrate heart development. We previously had performed four modified differential display (DD) screens in the chick embryo to identify genes that may be involved in CNC and heart development. Full‐length sequence of one of the DD clones has been obtained and identified as chick PINCH‐1. This particularly interesting new cysteine‐histidine–rich protein contains five protein‐binding LIM domains (five double zinc fingers), a nuclear localization signal, and a nuclear export signal, allowing it to participate in integrin and growth factor signaling and possibly act as a transcription factor. We show here for the first time that chick PINCH‐1 is expressed in neural crest cells, both in the neural fold and cardiac OFT, and is also expressed in mesoderm derived‐structures, including the myocardium, during avian embryogenesis. The normal expression pattern and overexpression in neural crest cell explants suggest that PINCH‐1 may be a regulator of neural crest cell adhesion and migration. Developmental Dynamics 235:152–162, 2006. © 2005 Wiley‐Liss, Inc.
Establishment and maintenance of planar epithelial cell polarity by asymmetric cadherin bridges: A computer model
Authors: Le Garrec Jean‐François , Lopez Philippe , Kerszberg Michel
Published: October 2005

Animal scales, hairs, feathers, and cilia are oriented due to cell polarization in the epithelial plane. Genes involved have been identified, but the signal and mechanism remain unknown. In Drosophila wing polarization, the action of a gradient of Frizzled activity is widely assumed; and cell–cell signalling by cadherins such as Flamingo surely plays a major role. We present a computer model where reading the Frizzled gradient occurs through biased, feedback‐reinforced formation of Flamingo‐based asymmetric intercellular complexes. Through these complexes neighboring cells are able to compare their Frizzled activity levels. Our computations are highly noise‐resistant and reproduce both wild‐type and all known mutant wing phenotypes; other phenotypes are predicted. The model puts stringent limits on a Frizzled activation signal, which should exhibit unusual properties: (1) the extracellular Frizzled signalling gradient should be counterdirectional—decreasing from proximal (P) to distal (D), whereas during polarization, the intracellular Frizzled gradient builds up from P to D; (2) the external gradient should be relatively weak and short‐lived, lest it prevent inversion of intracellular Frizzled. These features, largely independent of model details, may provide useful clues for future experimental efforts. Developmental Dynamics 235:235–246, 2006. © 2005 Wiley‐Liss, Inc.
A novel mutant phenotype implicates dicephalic in cyst formation in the Drosophila ovary
Authors: McCaffrey Ruth , St Johnston Daniel , González‐Reyes Acaimo
Published: October 2005

The establishment of polarity in Drosophila requires the correct specification of the oocyte in early stages of oogenesis, its positioning at the posterior of the egg chamber, and signalling events between the oocyte and the adjacent posterior follicle cells. As a consequence, the anterior‐posterior and the dorsal‐ventral axes are fixed. The posterior localisation of the oocyte depends on cadherin‐mediated adhesion between the oocyte and the follicle cells. Here we show that dicephalic mutants affect the posterior positioning of the oocyte without interfering with oocyte specification in the germarium. Unlike other mutants that also affect the posterior placement of the oocyte, dicephalic mutants affect neither gurken expression nor karyosome formation during meiosis. By analysing in detail the mutant phenotypes of dicephalic, we find that cyst formation in mutant germaria is defective and that it shares some similarities with cysts that lack DE‐cadherin in the germline cells. We propose a model in which dicephalic is involved in the proper adhesion between the oocyte and the somatic follicle cells. Developmental Dynamics 235:908–917, 2006. © 2005 Wiley‐Liss, Inc.
Expression patterns of Wnt genes during development of an anterior part of the chicken eye
Authors: Fokina Valentina M. , Frolova Elena I.
Published: October 2005

To address the roles of Wnts in the development of the anterior eye, we used a chicken model to perform comprehensive expression analysis of all Wnt genes during anterior eye development. In analyzing the available genomic sequences, we found that the chicken genome encodes 18 Wnt proteins that are homologous to corresponding human and mouse proteins. The mRNA sequences for 12 chicken Wnt genes are available in GenBank, and mRNAs for six other Wnt genes (Wnt2, Wnt5b, Wnt7b, Wnt8b, Wnt9b, and Wnt16) were identified and cloned based on the homology to the genes from other species. In addition, we found that chicken Wnt3a and Wnt7b genes encode two alternative mRNA isoforms containing different first exons. Following in situ hybridization, we found that out of 18 Wnt genes, 11 genes were expressed in the anterior eye, exhibiting distinct temporal‐spatial patterns. Several Wnts were expressed in the lens, including Wnt2 and Wnt2b in the anterior epithelium and Wnt5a, Wnt5b, Wnt7a, and Wnt7b in the differentiating lens fiber cells. In the cornea, we detected Wnt3a, Wnt6, and Wnt9b in the ocular surface ectoderm, including the corneal epithelium, and Wnt9a in the corneal endothelium from the onset of its differentiation. In the optic cup, Wnt2, Wnt2b, and Wnt9a were localized in the rim of the optic cup (presumptive iris), while Wnt5a and Wnt16 were detected in the ciliary epithelium/iris zone of the differentiated optic cup, and Wnt6 was expressed in the iridial mesenchyme. These data suggest that Wnt signaling might play important roles in anterior eye development. Developmental Dynamics 235:496–505, 2006. © 2005 Wiley‐Liss, Inc.
Epithelial transformations in the establishment of the blood–gas barrier in the developing chick embryo lung
Authors: Makanya A.N. , Hlushchuk R. , Duncker H.‐R. , Draeger A. , Djonov V.
Published: October 2005

The tall epithelium of the developing chick embryo lung is converted to a squamous one, which participates in formation of the thin blood–gas barrier. We show that this conversion occurred through processes resembling exocrine secretion. Initially, cells formed intraluminal protrusions (aposomes), and then transcellular double membranes were established. Gaps between the membranes opened, thus, severing the aposome from the cell. Alternatively, aposomes were squeezed out by adjacent cells or were spontaneously constricted and extruded. As a third mechanism, formation and fusion of severed vesicles or vacuoles below the aposome and their fusion with the apicolateral plasma membrane resulted in severing of the aposome. The atria started to form by progressive epithelial attenuation and subsequent invasion of the surrounding mesenchyme at regions delineated by subepithelial α‐smooth muscle actin–positive cells. Further epithelial attenuation was achieved by vacuolation; rupture of such vacuoles with resultant numerous microfolds and microvilli, which were abscised to accomplish a smooth squamous epithelium just before hatching. Developmental Dynamics 235:68–81, 2006. © 2005 Wiley‐Liss, Inc.
Spatio‐temporal expression of MRF4 transcripts and protein during Xenopus laevis embryogenesis
Authors: Della Gaspera Bruno , Sequeira Ines , Charbonnier Frederic , Becker Christel , Shi De‐Li , Chanoine Christophe
Published: October 2005

Whereas there have been extensive studies of the expression of XMyf5 and XMyoD during Xenopus embryogenesis, nothing is known about the spatio‐temporal accumulation of XMRF4 transcripts and protein. In this report, we describe the cloning and characterization of two full‐length MRF4 cDNAs and of their proximal promoters in Xenopus laevis. The comparison of the relative transcript levels of the XMRF4‐a and ‐b genes in developing and adult muscles is highly suggestive of specific functions for the corresponding XMRF4 proteins. Whole‐mount embryo in situ hybridization revealed the first XMRF4 transcripts in the more differentiated anterior myocytes of the embryo when the myosin heavy chain E3 mRNA begins to be detectable. XMRF4 mRNA accumulation later extended posteriorly but was never detected in the posterior unsegmented mesoderm, in contrast to XMyoD and XMyf‐5. Whole‐mount embryo immunohistochemistry revealed that XMRF4 protein accumulated in somite nuclei slightly after XMRF4 transcripts. Developmental Dynamics 235:524–529, 2006. © 2005 Wiley‐Liss, Inc.
Transforming growth factor‐β induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells
Authors: Compton Leigh A. , Potash Dru A. , Mundell Nathan A. , Barnett Joey V.
Published: October 2005

During embryogenesis, epicardial cells undergo epithelial–mesenchymal transformation (EMT), invade the myocardium, and differentiate into components of the coronary vasculature, including smooth muscle cells. We tested the hypothesis that transforming growth factor‐β (TGFβ) stimulates EMT and smooth muscle differentiation of epicardial cells. In epicardial explants, TGFβ1 and TGFβ2 induce loss of epithelial morphology, cytokeratin, and membrane‐associated Zonula Occludens‐1 and increase the smooth muscle markers calponin and caldesmon. Inhibition of activin receptor‐like kinase (ALK) 5 blocks these effects, whereas constitutively active (ca) ALK5 increases cell invasion by 42%. Overexpression of Smad 3 did not mimic the effects of caALK5. Inhibition of p160 rho kinase or p38 MAP kinase prevented the loss of epithelial morphology in response to TGFβ, whereas only inhibition of p160 rho kinase blocked TGFβ‐stimulated caldesmon expression. These data demonstrate that TGFβ stimulates loss of epithelial character and smooth muscle differentiation in epicardial cells by means of a mechanism that requires ALK5 and p160 rho kinase. Developmental Dynamics 235:82–93, 2006. © 2005 Wiley‐Liss, Inc.
Wingless signaling in a large insect, the blowfly Lucilia sericata: A beautiful example of evolutionary developmental biology
Authors: Mellenthin Katja , Fahmy Khalid , Ali Reda A. , Hunding Axel , Da Rocha Sol , Baumgartner Stefan
Published: October 2005

Blowflies are the primary facultative agent in causing myiasis of domestic sheep in the whole world and, at the same time, it is an important tool for forensic medicine. Surprisingly, and in contrast to its importance, almost no data regarding the embryology and molecular markers are known for this insect. In this report, we present a detailed description of the blowfly Lucilia sericata embryogenesis and of imaginal disc development. The embryogenesis of Lucilia strongly resembles that of Drosophila, despite their apparent size difference. Moreover, imaginal disc development appears to be equally well conserved. Through cloning, expression, and functional studies, we show that the Lucilia Wingless (Wg) protein is highly conserved between the two species. We further show that parasegments are established in Lucilia, however, engrailed expression shows a more dynamic expression pattern than expected in comparison to Drosophila. Over‐expression of Lucilia Wingless in Drosophila shows wingless‐like wing phenotypes, suggesting that Lucilia Wingless blocks the signalling activity of Drosophila Wingless. Upon injection of wg dsRNA, we observe a “lawn of denticle” phenotype, closely resembling that of Drosophila. Due to the large size of the insect, the distance over which Wingless exerts signalling activity is up to three times larger than in Drosophila, yet the consequences are very similar. Our data demonstrate long‐range wingless signaling mechanisms adapted for patterning large domains of naked cuticle and suggest signaling properties of Lucilia Wingless that are distinct from those of Drosophila Wingless. Developmental Dynamics 235:347–360, 2006. © 2005 Wiley‐Liss, Inc.
Modeling past and future alpine permafrost distribution in the Colorado Front Range
Authors: Janke Jason R.
Published: October 2005

Rock glaciers, a feature associated with at least discontinuous permafrost, provide important topoclimatic information. Active and inactive rock glaciers can be used to model current permafrost distribution. Relict rock glacier locations provide paleoclimatic information to infer past conditions. Future warmer climates could cause permafrost zones to shrink and initiate slope instability hazards such as debris flows or rockslides, thus modeling change remains imperative. This research examines potential past and future permafrost distribution in the Colorado Front Range by calibrating an existing permafrost model using a standard adiabatic rate for mountains (0·5 °C per 100 m) for a 4 °C range of cooler and warmer temperatures. According to the model, permafrost currently covers about 12 per cent (326·1 km2) of the entire study area (2721·5 km2). In a 4 °C cooler climate 73·7 per cent (2004·4 km2) of the study area could be covered by permafrost, whereas in a 4°C warmer climate almost no permafrost would be found. Permafrost would be reduced severely by 93·9 per cent (a loss of 306·2 km2) in a 2·0 °C warmer climate; however, permafrost will likely respond slowly to change. Relict rock glacier distribution indicates that mean annual air temperature (MAAT) was once at least some 3·0 to 4·0 °C cooler during the Pleistocene, with permafrost extending some 600–700 m lower than today. The model is effective at identifying temperature sensitive areas for future monitoring; however, other feedback mechanisms such as precipitation are neglected. Copyright © 2005 John Wiley & Sons, Ltd.
The form and function of headwater streams based on field and modeling investigations in the southern Appalachian Mountains
Authors: Adams Rebecca Kavage , Spotila James A.
Published: October 2005

Headwater streams drain the majority of most landscapes, yet less is known about their morphology and sediment transport processes than for lowland rivers. We have studied headwater channel form, discharge and erosive power in the humid, moderate‐relief Valley and Ridge and Blue Ridge provinces of the Appalachian Mountains. Field observations from nine headwater (<2 km2drainage area), mixed bedrock–alluvial channels in a variety of boundary conditions demonstrate variation with respect to slope‐area channel initiation, basic morphology, slope distribution, hydraulic geometry, substrate grain size and role of woody debris. These channels display only some of the typical downstream trends expected of larger, lowland rivers. Variations are controlled mainly by differences in bedrock resistance, from the formation level down to short‐wavelength, outcrop‐scale variations. Hydrologic modeling on these ungauged channels estimates the recurrence of channel‐filling discharge and its ability to erode the channel bed. Two‐year recurrence discharge is generally larger and closer to bankfull height in the Valley and Ridge, due to low soil infiltration capacity. Discharge that fills the channel to its surveyed bankfull form is variable, generally exceeding two‐year flows at small drainage areas (<0·5 km2) and being exceeded by them at greater drainage areas. This suggests bankfull is not controlled by the same recurrence storm throughout a channel or physiographic region. Stream power and relative competence are also variable. These heterogeneities contrast relations observed in larger streams and illustrate the sensitivity of headwater channels to local knickpoints of resistant bedrock and armoring of channels by influx of coarse debris from hillslopes. The general lack of predictable trends or functional relationships among hydraulic variables and the close coupling of channel form and function with local boundary conditions indicate that headwater streams pose a significant challenge to landscape evolution modeling. Copyright © 2005 John Wiley & Sons, Ltd.
Fine allelotyping of Erbb2‐induced mammary tumors in mice reveals multiple discontinuous candidate regions of tumor‐suppressor loci
Authors: Cool Marc , Depault François , Jolicoeur Paul
Published: October 2005

Loss of heterozygosity (LOH) at human chromosome bands 1p32–36 and 10q23–26 is frequent in various human tumors, including breast cancers, and is thought to reflect the loss of tumor‐suppressor genes (TSGs). To map such genes, high‐resolution LOH analysis was performed on 93 Erbb2‐induced mammary tumors from (BALB/c × C57BL/6) F1 MMTV/Erbb2 transgenic mice. A panel of 24 microsatellite markers specific to the region of mouse chr4, homologous to human 1p31–36, and 16 markers specific to the mouse chr19 region, homologous to human 10q23–26 were used. In addition, lower‐density mapping was performed on the remaining portion of mouse chr4 [homologous to human 9p13, 9p21–24, 9q21–22, 9q31–34 (12 markers)] and chr19 [homologous to 9q21, 9p24, 11q12–13 (9 markers)]. Several distinct, discrete, and discontinuous LOH regions flanked by areas of heterozygosity were identified, 22 on chr4 and 14 on chr19. Among these, 13 were mapped in the region of homology with human 1p31–36 (between D4Mit153 and D4Mit254) and 9 in the region of homology with human 10q23–26 (between D19Mit46 and D19Mit6). Although several LOH loci span a large interval, many are relatively short (1–4 Mb), and a few span an interval of <1 Mb. This allelotyping represents the highest density of LOH loci yet mapped in these chromosomal regions. The presence of numerous LOH regions in alternation with regions of heterozygosity, consistent with mitotic recombination as a mechanism for generating such a mosaic pattern, suggests the presence of several TSGs in these regions and should facilitate their identification. © 2005 Wiley‐Liss, Inc.
Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: A possible hot spot?
Authors: Cascón Alberto , Montero‐Conde Cristina , Ruiz‐Llorente Sergio , Mercadillo Fátima , Letón Rocío , Rodríguez‐Antona Cristina , Martínez‐Delgado Beatriz , Delgado Manuel , Díez Alberto , Rovira Adela , Díaz José Ángel , Robledo Mercedes
Published: October 2005

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise in the adrenal medulla and the extra‐adrenal paraganglia, respectively. Inheritance of these tumors is mainly a result of mutations affecting the VHL, RET, NF1, and SDH genes. Germ‐line mutations of the SDH genes have been found to account for nearly 10% of apparently sporadic cases. Nevertheless, alterations other than point mutations have not yet been well characterized. In this study, we investigated the frequency of gross SDH deletions in 24 patients who tested negative for point mutations and had at least one of the recommended features for genetic testing. For this purpose, we used a technique that is easy to implement in the lab to specifically detect gross deletions affecting SDHB, SDHC, and SDHD. We identified 3 heterozygous SDHB deletions (3/24) in 3 independent cases with paraganglioma: 1 whole SDHB deletion and 2 deletions exclusively affecting exon 1. These latter mutations match the unique gross deletion previously reported, indicating this region could be a hot spot for gross SDHB deletions. It seems likely that these alterations can account for a considerable number of both familial and apparently sporadic paraganglioma cases. Although this is the first report describing the presence of gross deletions in patients with apparently sporadic paragangliomas, the extra‐adrenal location of the tumor seems to constitute a determining factor for whether to include these patients in genetic testing for gross deletions in the SDHB gene. © 2005 Wiley‐Liss, Inc.
Synthetic Studies on Coenzyme Q10
Authors: Yu Xiong‐Jie , Chen Fen‐Er , Dai Hui‐Fang , Chen Xu‐Xiang , Kuang Yun‐Yan , Xie Bin
Published: October 2005

A practical, highly stereoselective ten‐step synthesis of coenzyme Q10 (1) has been accomplished (overall yield ca. 28%), starting from commercially available 2,3‐dimethoxy‐5‐methylbenzoquinone (Scheme). The introduction of the first side‐chain isoprenyl group with (E)‐configuration (compound 6) was realized by means of a coupling reaction of the aromatic system 3 with oxirane, followed by Swern oxidation and Wittig olefination. The tosyl (Ts) group in the sulfone 9 was selectively removed with sodium naphthalenide in THF to afford 1.
Intramolecular Photocyclization of 2‐Acylphenyl Methacrylates: a Convenient Access to 4,5‐Dihydro‐1,4‐epoxy‐2‐benzoxepin‐3(1H)‐ones (= Benzo[c]‐6,8‐dioxabicyclo[3.2.1]octan‐7‐ones
Authors: Nishio Takehiko , Sakurai Nobuharu , Iba Kaoru , Hamano Yo‐ichi , Sakamoto Masami
Published: October 2005

The photochemical reactions of 2‐acylphenyl methacrylates (= 2‐acylphenyl 2‐methylprop‐2‐enoates) 1 were investigated. Irradiation of 2‐acylphenyl methacrylates 1a–d in MeCN gave the tricyclic lactones 2a–d in good yields, together with a small amount of OCO bond cleavage product, the 2‐acylphenols 3a–d (Scheme 2, Table). The formation of the tricyclic lactones 2 probably follows a mechanism involving a 1,7‐diradical through ζ‐H abstraction (1,8‐H transfer) by the excited carbonyl O‐atom (Scheme 3). Irradiation of 2‐acylphenyl tiglate (= 2‐acylphenyl (2E)‐2‐methylbut‐2‐enoate) 1e and 2‐acylphenyl methacrylates 1g–i, substituted by a MeO group (δ‐H) at the 3,5‐positions of the phenyl group, also gave the tricyclic lactones 2e and 2g–i, but in low yields. On the other hand, no H‐abstraction products were observed on irridation of 2‐(ethoxycarbonyl)phenyl methacrylate 1f, of 2‐acylphenyl methacrylate 1j which is substituted by a Me group (γ‐H) at the 3,5‐positions of the phenyl group, and of 1k with an OH group at the 3‐position of the phenyl group.
Multiflorane Triterpene Esters from the Seeds of Trichosanthes kirilowii
Authors: Wu Tao , Cheng Xue‐Mei , Bligh S. W. Annie , Chou Gui‐Xin , Wang Zheng‐Tao , Bashall Alan , Branford‐White Chris
Published: October 2005

Two new multiflorane triterpene esters, (3α,7β)‐3,7,29‐trihydroxymultiflor‐8‐ene‐3,29‐diyl dibenzoate (2) and (3α)‐3,29‐dihydroxy‐7‐oxomultiflor‐8‐ene‐3,29‐diyl dibenzoate (3) have been isolated from the CHCl3 extract of the seeds of Trichosanthes kirilowii, together with two known compounds, (3α,5α,22E)‐24‐ethylcholesta‐7,22,25(27)‐trien‐3‐ol and darutigenol. The structures of the new compounds were elucidated on the basis of extensive NMR experiments, and by means of an X‐ray crystallographic analysis of 2. A preliminary cytotoxicity assay showed that 2 and 3 are basically inactive against the K562 cell line.
Synthesis and Reactions of a New Cyclobutanethione Derivative
Authors: Mlostoń Grzegorz , Majchrzak Agnieszka , Rutkowska Marzena , Woznicka Marta , Linden Anthony , Heimgartner Heinz
Published: October 2005

The 3,3‐dichloro‐2,2,4,4‐tetramethylcyclobutanethione (4b) was prepared from the parent diketone by successive reaction with PCl5 and Lawesson reagent in pyridine. This new thioketone 4b was transformed into 1‐chlorocyclobutanesulfanyl chloride 5 and chloro 1‐chlorocyclobutyl disulfide 9 by treatment with PCl5 and SCl2, respectively, in chlorinated solvents (Schemes 1 and 2). These products reacted with S‐ and P‐nucleophiles by substitution of Cl− at the S‐atom; e.g., the reaction with 4b yielded the di‐ and trisulfides 6b and 11, respectively. Surprisingly, only pentasulfide 12 was formed in the reaction of 9 with thiobenzophenone (Scheme 3). In contrast to 5 and 9, the corresponding chloro 1‐chlorocyclobutyl trisulfide 13 could not be detected, but reacted immediately with the starting thioketone 4b to give the tetrasulfide 14 (Scheme 4). Oxidation of 4b with 3‐chloroperbenzoic acid (mCPBA) yielded the corresponding thione oxides (= sulfine) 15, which underwent 1,3‐dipolar cycloadditions with thioketones 3a and 4b (Scheme 5). Furthermore, 4b was shown to be a good dipolarophile in reactions with thiocarbonylium methanides (Scheme 6) and iminium ylides (= azomethine ylides; Scheme 7). In the case of phenyl azide, the reaction with 4b gave the symmetrical trithiolane 25 (Scheme 8).
Structures and Absolute Configurations of Three 7,8‐Secolabdane Diterpenes from the Chinese Liverwort Pallavicinia ambigua
Authors: Li Zi‐Jing , Lou Hong‐Xiang , Yu Wen‐Tao , Fan Pei‐Hong , Ren Dong‐Mei , Ma Bin , Ji Mei
Published: October 2005

The known 7,8‐secolabdane type diterpenoids neopallavicinin (1), pallavicinin (2), and 18‐hydroxypallavicinin (3) were isolated from Pallavicinia ambigua, and their structures were determined. The X‐ray crystal structure of 1 was solved, and, in combination with CD and NMR studies, the absolute configurations of 1–3 were established. A possible biogenetic pathway for 1 and 2 from a single labdane precursor is proposed.
para‐Sulfonated Calixarenes Used as Synthetic Receptors for Complexing Photolabile Cholinergic Ligand
Authors: Specht Alexandre , Ziarelli Fabio , Bernard Philippe , Goeldner Maurice , Peng Ling
Published: October 2005

The water‐soluble tetra‐, hexa‐ and octasulfonated calix[4]arenes, calix[6]arenes, and calix[8]arenes 1–3, respectively, were investigated as potential synthetic receptors for photolabile cholinergic ligand A, a photolytic precursor of choline. Ligand A is a bifunctional molecule carrying a photolabile 2‐nitrobenzyl group at one end and a choline moiety at the other end. Results from NMR studies have shown that calixarenes 1–3 form stable 1 : 1 complexes with A, having similar binding potential to that observed with the cholinergic enzymes acetylcholinesterase and butyrylcholinesterase. Further studies have suggested that calix[8]arene forms a ditopic complex by binding concomitantly to both the cationic choline moiety and the aromatic photolabile group of A, whereas calix[4]arene and calix[6]arene form monotopic complexes with A. The ditopic complex between calix[8]arene and A results from mutually induced fitting process, while the monotopic complexes between calix[4]arene and A can be regulated by pH: at neutral pH, calix[4]arene specifically binds the cationic choline moiety, while, at acidic pH, it complexes unselectively both the cationic choline moiety and the aromatic group of A. Our results show that para‐sulfonated calixarenes are versatile artificial receptors which bind in various ways to the bifunctional photolabile cholinergic ligand A, depending on their size, geometry, and state of protonation.
Three New Polyoxypregnane Glycosides from Marsdenia tenacissima
Authors: Deng Jun , Liao Zhixin , Chen Daofeng
Published: October 2005

Three new polyoxypregnane glycosides, marsdenosides I–K (1–3), were isolated from the stem of Marsdenia tenacissima. The structures were elucidated on the basis of in‐depth spectroscopic analyses, and by means of chemical evidence. Marsdenoside I (= (3β,5α,11α,12β,14β,17α,20R)‐3‐[(2,6‐dideoxy‐4‐O‐(6‐deoxy‐3‐O‐methyl‐β‐D‐allopyranosyl)‐3‐O‐methyl‐β‐D‐arabino‐hexopyranosyl)oxy]‐8,20 : 11,20‐diepoxypregnane‐12,14‐diol; 1) is the first C21 steroidal glycoside with a rigid cage. Also, the isolation of 1 demonstrated that tenacigenin A (1a) is a true natural product as well, rather than an artifact.
Synthesis of 2′‐O‐[(Triisopropylsilyl)oxy]methyl (= tom)‐Protected Ribonucleoside Phosphoramidites Containing Various Nucleobase Analogues
Authors: Porcher Sébastien , Pitsch Stefan
Published: October 2005

The first results of a study aiming at an efficient preparation of a large variety of 2′‐O‐[(triisopropylsilyl)oxy]methyl(= tom)‐protected ribonucleoside phosphoramidite building blocks containing modified nucleobases are reported. All of the here presented nucleosides have already been incorporated into RNA sequences by several other groups, employing 2′‐O‐tbdms‐ or 2′‐O‐tom‐protected phosphoramidite building blocks (tbdms = (tert‐butyl)dimethylsilyl). We now optimized existing reactions, developed some new and shorter synthetic strategies, and sometimes introduced other nucleobase‐protecting groups. The 2′‐O‐tom, 5′‐O‐(dimethoxytrityl)‐protected ribonucleosides N2‐acetylisocytidine 5, O2‐(diphenylcarbamoyl)‐N6‐isobutyrylisoguanosine 8, N6‐isobutyryl‐N2‐(methoxyacetyl)purine‐2,6‐diamine ribonucleoside (= N8‐isobutyryl‐2‐[(methoxyacetyl)amino]adenosine) 11, 5‐methyluridine 13, and 5,6‐dihydrouridine 15 were prepared by first introducing the nucleobase protecting groups and the dimethoxytrityl group, respectively, followed by the 2′‐O‐tom group (Scheme 1). The other presented 2′‐O‐tom, 5′‐O‐(dimethoxytrityl)‐protected ribonucleosides inosine 17, 1‐methylinosine 18, N6‐isopent‐2‐enyladenosine 21, N6‐methyladenosine 22, N6,N6‐dimethyladenosine 23, 1‐methylguanosine 25, N2‐methylguanosine 27, N2,N2‐dimethylguanosine 29, N6‐(chloroacetyl)‐1‐methyladenosine 32, N6‐{{{(1S,2R)‐2‐{[(tert‐butyl)dimethylsilyl]oxy}‐1‐{[2‐(4‐nitrophenyl)ethoxy]carbonyl}propyl}amino}carbonyl}}adenosine 34 (derived from L‐threonine) and N4‐acetyl‐5‐methylcytidine 36 were prepared by nucleobase transformation reactions from standard, already 2′‐O‐tom‐protected ribonucleosides (Schemes 2–4). Finally, all these nucleosides were transformed into the corresponding phosphoramidites 37–52 (Scheme 5), which are fully compatible with the assembly and deprotection conditions for standard RNA synthesis based on 2′‐O‐tom‐protected monomeric building blocks.
Computational NMR Spectroscopy of Transition‐Metal/Nitroimidazole Complexes: Theoretical Investigation of Potential Radiosensitizers
Authors: Ramalho Teodorico C. , Bühl Michael , Figueroa‐Villar José Daniel , de Alencastro Ricardo Bicca
Published: October 2005

The computed chemical shifts of transition‐metal complexes with dimetridazole (= 1,2‐dimethyl‐5‐nitro‐1H‐imidazole; 1), a prototypical nitro‐imidazole‐based radiosensitizer, are reported at the GIAO‐BP86 and ‐B3LYP levels for BP86/ECP1‐optimized geometries. These complexes comprise [MCl2(1)2] (M = Zn, Pd, Pt), [RuCl2(DMSO)2(1)2], and [Rh2(O2CMe)4(1)2]. Available δ(1H) and δ(15N) values, and Δδ(1H) and Δδ(15N) coordination shifts are well‐reproduced theoretically, provided solvation and relativistic effects are taken into account by means of a polarizable continuum model and suitable methods including spin–orbit (SO) coupling, respectively. These effects are particularly important for the metal‐coordinated N‐atom, where the contributions from solvation and relativity can affect δ(15N) and Δδ(15N) values up to 10–20 ppm. The 195Pt chemical shifts of cis‐ and trans‐[PtCl2(1)2] are well‐reproduced using the zero‐order regular approximation including SO coupling (ZORA‐SO). Predictions are reported for 99Ru and 103Rh chemical shifts, which suggest that these metal centers could be used as additional, sensitive NMR probes in their complexes with nitro‐imidazoles.
Synthesis of New Resorcinarenes Under Alkaline Conditions
Authors: Bourgeois Jean‐Marc , Stoeckli‐Evans Helen
Published: October 2005

The preparation of functionalized resorcinarenes is described. Thus, 2‐nitroresorcinol (= 2‐nitrobenzene‐1,2‐diol), 2‐acetylresorcinol (= 1‐(2,6‐dihydroxyphenyl)ethanone), and 2,6‐dihydroxybenzoic acid were treated with formaldehyde in alkaline medium to give the corresponding resorcinarenes1–3(Scheme 1). This method is also applicable for resorcinol (= benzene‐1,3‐diol) itself, but the yields are poorer. In this case, the molecule formed is the simplest resorcinarene4on which a number of substituents can be inserted between the two OH groups. Thus, bromation of4yields5(Scheme 2). Some properties and conformations of these new products are discussed, and the X‐ray crystal structures of the nitro and bromo compounds1and5, respectively, are presented.
Squadinorlignoside: A Novel 7,9′‐Dinorlignan from the Stems of Annona squamosa
Authors: Yang Yu‐Liang , Chang Fang‐Rong , Wu Yang‐Chang
Published: October 2005

Two new polar lignans, i.e., squadinorlignoside (= 4‐[(1E)‐1‐(hydroxymethyl)‐3‐(4‐hydroxyphenyl)prop‐1‐en‐1‐yl]phenyl β‐D‐glucopyranoside; 1) and (6R,7R,8S)‐7a‐[(β‐D‐glucopyranosyl)oxy]‐1‐methoxyisolariciresinol (2) were isolated from the stems of Annona squamosa, together with eight known lignans and five known neolignans (compounds 3–15; Fig. 1). All of these constituents are reported for the first time from the genus Annona. The structures, absolute configurations, and selected conformational aspects of the new compounds were elucidated spectroscopically. Compound 1 is the first example of a 7,9′‐dinorlignan natural product.
Enantioselective Syntheses and Fragrance Properties of the Four Stereoisomers of Magnolione® (Magnolia Ketone)
Authors: Stang Andrea Quendolin , Helmchen Günter
Published: October 2005

Enantioselective total syntheses of the four stereoisomers of the fragrance Magnolione® (1) are described. Key step is a Pd‐catalyzed asymmetric allylic alkylation displaying enantiomer excess of ≥ 99% (Scheme 2). The resultant methyl α‐acetyl‐2‐pentylcyclopent‐2‐ene‐1‐acetate) was subjected to demethoxycarbonylation, carbonyl protection by acetalization, and epoxidation (Schemes 2 and 3). Subsequent Lewis acid catalyzed epoxide/ ketone rearrangement followed by deprotection gave cis/trans mixtures of Magnolione® in 28% overall yield (Scheme 3). The cis/trans isomers were separated by prep. HPLC, and fragrance properties as well as odor threshold values were determined (Table 2).