bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic and life‐history patterns in a population of ring‐tailed lemurs (Lemur catta) at Beza Mahafaly Reserve, Madagascar: A 15‐year perspective
Authors: Gould Lisa , Sussman R.W. , Sauther Michelle L.
Published: January 2003

Over 15 field seasons (1987–2001), we collected census and life‐history data on a population of individually identified ring‐tailed lemurs at the Beza Mahafaly Reserve, Madagascar. No significant difference was found in population size over the study period, though a marked decline in the population occurred following a 2‐year drought. The population rebounded rapidly after the immediate postdrought period. There was nearly a complete replacement of individuals over the study period. Average group size is 11.5 animals, and adult male to female sex ratio is 0.92. Most females reproduce annually, and the average fecundity rate is 84.3%. The greatest variability in fecundity is found among old females. We suggest that ring‐tailed lemur females follow an “income breeding” strategy, i.e., females use maximum resources during reproduction rather than relying on fat stores, as do “capital breeders.” Infant mortality to 1 year of age in a nondrought year is 52%, higher than infant mortality in small to medium‐sized anthropoids. The oldest known female was 18 years old in 2001. We suggest that 18–20 years may represent the maximum life‐span for wild ring‐tailed lemurs. Because males regularly emigrate from the population, we have no data regarding male life‐span; however, there is some indication that males do not survive as long as females. Group fission has occurred three times: twice from one parent group living in the driest area of the reserve, with the most dispersed food resources. We suggest that the reproductive strategy that has evolved in this species, wherein females reproduce early in life and annually until old age, is a response to the unusual climate and environmental conditions under which Lemur catta has evolved. Am J Phys Anthropol 120:182–194, 2003. © 2003 Wiley‐Liss, Inc.
Genetic diversity of JC virus in the modern Filipino population: Implications for the peopling of the Philippines
Authors: Miranda Jasmin Jiji , Sugimoto Chie , Paraguison Rubigilda , Takasaka Tomokazu , Zheng Huai‐Ying , Yogo Yoshiaki
Published: January 2003

The Philippines is generally believed to have been established by various peoples who migrated from neighboring areas. To gain new insights into the peopling of the Philippines, we used the JC virus (JCV) genotyping approach. We collected about 50 urine samples on each of two representative islands of the Philippines, Luzon and Cebu. DNA was extracted from the urine samples and used to amplify the 610‐bp region (IG region) of the viral genome. For each island, we determined about 20 IG sequences, from which a neighbor‐joining phylogenetic tree was constructed to classify the JCV isolates detected into distinct genotypes. The predominant genotype detected was SC, the Southeast Asian genotype. Minor JCV genotypes were SC/Phi, B1‐a, and B3. SC/Phi was a subcluster of SC and has not been detected in areas other than the Philippines. B1‐a was detected previously in mainland China, Pamalican Island (Palawan, Philippines), and Taiwan (an aboriginal tribe). B3 was classified in this study into two subgroups, one (B3‐a) containing three Luzon isolates and several Chinese, Thai, and Uzbek isolates, the other (B3‐b) containing two Luzon, one Cebu, and one Indonesian isolate. These findings suggest that the modern Filipino population was formed not only by Southeast Asians carrying SC but also by a few distinct ethnic groups carrying SC/Phi, B1‐a, and B3‐a or ‐b. Am J Phys Anthropol 120:125–132, 2003. © 2003 Wiley‐Liss, Inc.
A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate
Authors: Van Der Knaap Marjo S. , Van Der Voorn Patrick , Barkhof Frederik , Van Coster Rudy , Krägeloh‐Mann Ingeborg , Feigenbaum Annette , Blaser Susan , Vles Johan S. H. , Rieckmann Peter , Pouwels Petra J. W.
Published: January 2003

We identified eight patients with a distinct magnetic resonance imaging pattern of inhomogeneous cerebral white matter abnormalities and selective involvement of brainstem and spinal tracts. Proton magnetic resonance imaging showed increased lactate in the abnormal white matter. Clinically, the patients had slowly progressive pyramidal, cerebellar, and dorsal column dysfunction. The uniform, highly characteristic magnetic resonance imaging pattern and the similarities in clinical and magnetic resonance spectroscopy findings provide evidence for a new disease entity. Autosomal recessive inheritance is likely.
Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS
Authors: Zhang Wenhua , Narayanan Malini , Friedlander Robert M.
Published: January 2003

The known neuroprotective effects of minocycline and creatine in animal models of amyotrophic lateral sclerosis (ALS) led us to examine whether the combination of these agents would result in increased neuroprotection. As previously reported, we confirmed in ALS mice that either minocycline or creatine treatment results in improvement in motor performance and extended survival. We report that combination of minocycline and creatine resulted in additive neuroprotection, suggesting this to be a novel potential strategy for the treatment of ALS. To our knowledge, this is the first report demonstrating additive neuroprotection of a combinatorial approach in a mouse model of ALS. Adding relevancy to our findings, minocycline and creatine, are relatively safe, cross the blood–brain barrier, and are currently available for human evaluation.
A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the pdx1 gene
Authors: Dey Runu , Mine Manuele , Desguerre Isabelle , Slama Abdelhamid , Van Den Berghe Loic , Brivet Michèle , Aral Bernard , Marsac Cécile
Published: January 2003

We report a case of neonatal congenital lactic acidosis associated with pyruvate dehydrogenase E3‐binding protein deficiency in a newborn girl. She had a severe encephalopathy, and magnetic resonance imaging of the brain showed large subependymal cysts and no basal ganglia lesions. She died 35 days after birth. We detected a novel homozygous deletion (620delC) in the PDX1 gene, which encodes for the E3BP subunit of the pyruvate dehydrogenase complex.
Homogene und heterogene Katalyse – Brückenschlag durch Oberflächen‐Organometallchemie
Authors: Copéret Christophe , Chabanas Mathieu , Petroff Saint‐Arroman Romain , Basset Jean‐Marie
Published: January 2003

Die Oberflächen‐Organometallchemie ist ein Gebiet der heterogenen Katalyse, das erst vor kurzem aus einer vergleichenden Analyse der homogenen und der heterogenen Katalyse hervorgegangen ist. In der chemischen Industrie wurde die heterogene Katalyse häufig bevorzugt, doch wurde die Entwicklung besserer Katalysatoren dadurch erschwert, dass zahlreiche verschiedene aktive Zentren vorliegen und diese zudem in zu geringer Zahl. Hierdurch wurde eine gezielte Verbesserung dieser Systeme verhindert – daher die empirische Natur der heterogenen Katalyse. Katalyse ist in erster Linie ein molekulares Phänomen, und es müssen wohldefinierte Organometallintermediate oder ‐übergangszustände auf Oberflächen beteiligt sein. Man muss daher in der Lage sein, ein wohldefiniertes aktives Zentrum aufzubauen, seine Katalysatorleistung zu testen und eine Struktur‐Aktivitäts‐Beziehung aufzustellen, die dann wiederum – wie bei der homogenen Katalyse – zur Entwicklung besserer Katalysatoren genutzt wird.

Die Oberflächen‐Organometallchemie überträgt die Konzepte und Methoden der molekularen Organometallchemie auf Oberflächen. So können über das Verständnis der Reaktion von Organometallkomplexen mit dem Träger, der als starrer Ligand aufgefasst werden kann, wohldefinierte Oberflächenspezies hergestellt werden. Durch diesen neuartigen Ansatz der heterogenen Katalyse kann man auf molekularem Niveau Einsichten in das Design neuer Katalysatoren erhalten; sogar die Entdeckung neuartiger Reaktionen ist möglich (Ziegler‐Natta‐Depolymerisation und Alkanmetathese). Obwohl sie schon seit mehr als 100 Jahre bekannt ist, kann die heterogene Katalyse auch heute noch verbessert werden – sie wird eine entscheidende Rolle bei der Lösung einiger der gegenwärtigen gesellschaftlichen Probleme spielen. Sie verspricht eine Antwort auf ökonomische und ökologische Probleme, denen sich die Industrie bei der Herstellung von Chemikalien (Agrochemikalien, Petrochemikalien, Pharmazeutika, Polymeren, Grundchemikalien) gegenüber sieht.
Titelbild: Angew. Chem. 2/2003
Authors: Copéret Christophe , Chabanas Mathieu , Petroff Saint‐Arroman Romain , Basset Jean‐Marie
Published: January 2003

Die Katalyseforschung baut Brücken zwischen Disziplinen. Das Titelbild zeigt die Oberflächen‐Organometallchemie als Bindeglied zwischen den zwei traditionellen Gebieten der Katalyse. Durch die Übertragung der Konzepte und Methoden der molekularen Organometallchemie auf Oberflächen werden die Erkenntnisse über die Reaktion der Organometallkomplexe mit dem Träger genutzt: Die Oberflächen‐Organometallchemie kann wohldefinierte Oberflächenspezies herstellen. Mehr dazu erfahren Sie im Aufsatz von Copéret, Basset et al. auf Seite 164ff.
Titelbild: Angew. Chem. 3/2003
Authors: Gatteschi Dante , Sessoli Roberta
Published: January 2003

Einzelmolekülmagnete wurden in den letzten Jahren intensiv erforscht. Das Titelbild zeigt eine gestufte Hystereseschleife als ein Indiz für resonantes Quantentunneln der Magnetisierung, ein Phänomen, das bei tiefen Temperaturen in Molekülen mit hohem Gesamtspin und hoher magnetischer Anisotropie beobachtet werden kann. Beispiele umfassen Mangan(III)‐Mangan(IV)‐Oxocluster und achtkernige Eisen(III)‐Cluster. Mehr zu den Eigenschaften solcher Einzelmolekülmagnete erfahren Sie in dem Aufsatz von D. Gatteschi und R. Sessoli auf S. 278 ff.
Quantentunneln der Magnetisierung und verwandte Phänomene in molekularen Materialien
Authors: Gatteschi Dante , Sessoli Roberta
Published: January 2003

Moleküle mit einer großen Zahl gekoppelter paramagnetischer Zentren werden gegenwärtig intensiv erforscht. Man hofft auf Eigenschaften zu treffen, die zwischen denen isolierter Paramagnete und klassischer Magnete liegen, und damit einen eindeutigen Nachweis für das Auftreten von Größenquantisierungseffekten in Magneten zu erhalten. Als Prüfsteine für neue Theorien dienten bislang die beiden Clusterfamilien Mn12 und Fe8. Man darf jedoch davon ausgehen, dass die Synthesechemie in naher Zukunft weitere Klassen mit ähnlichen oder gar besseren Eigenschaften hervorbringt. Als eine Voraussetzung hierfür müssen die Beziehungen zwischen Struktur und Eigenschaften des Moleküls klar verstanden und Konzepte wie Quantentunneln, Quantenkohärenz oder Quantenoszillation gut bekannt sein. Ziel dieses Aufsatzes ist es, die notwendigen Grundlagen zum Verständnis der Größenquantisierungseffekte zusammenzufassen und einen kritischen Überblick über die Entwicklung dieses jungen Forschungsgebietes zu geben.
Homogeneous and Heterogeneous Catalysis: Bridging the Gap through Surface Organometallic Chemistry
Authors: Copéret Christophe , Chabanas Mathieu , Petroff Saint‐Arroman Romain , Basset Jean‐Marie
Published: January 2003

Surface organometallic chemistry is an area of heterogeneous catalysis which has recently emerged as a result of a comparative analysis of homogeneous and heterogeneous catalysis. The chemical industry has often favored heterogeneous catalysis, but the development of better catalysts has been hindered by the presence of numerous kinds of active sites and also by the low concentration of active sites. These factors have precluded a rational improvement of these systems, hence the empirical nature of heterogeneous catalysis. Catalysis is primarily a molecular phenomenon, and it must involve well‐defined surface organometallic intermediates and/or transition states. Thus, one must be able to construct a well‐defined active site, test its catalytic performance, and assess a structure–activity relationship, which will be used, in turn—as in homogeneous catalysis—to design better catalysts.

By the transfer of the concepts and tools of molecular organometallic chemistry to surfaces, surface organometallic chemistry can generate well‐defined surface species by understanding the reaction of organometallic complexes with the support, which can be considered as a rigid ligand. This new approach to heterogeneous catalysis can bring molecular insight to the design of new catalysts and even allow the discovery of new reactions (Ziegler–Natta depolymerization and alkane metathesis). After more than a century of existence, heterogeneous catalysis can still be improved and will play a crucial role in solving current problems. It offers an answer to economical and environmental problems faced by industry in the production of molecules (agrochemicals, petrochemicals, pharmaceuticals, polymers, basic chemicals).
Cover Picture: Angew. Chem. Int. Ed. 2/2003
Authors: Copéret Christophe , Chabanas Mathieu , Petroff Saint‐Arroman Romain , Basset Jean‐Marie
Published: January 2003

Catalysis research builds bridges between disciplines. The cover picture shows the linking position of surface organometallic chemistry between the two traditional areas of catalysis. The transfer of the concepts and tools of molecular organometallic chemistry to surfaces leads to the generation of well‐defined surface species. The success of this approach results from understanding the reactions of organometallic complexes with the support. More about this field can be found in the review by Copéret, Basset, et al. on page 156ff.
Cover Picture: Angew. Chem. Int. Ed. 3/2003
Authors: Gatteschi Dante , Sessoli Roberta
Published: January 2003

Single‐Molecule Magnets have received a lot of attention over the last decade. The cover picture shows the stepped magnetic hysteresis loop, which is the fingerprint of the resonant quantum tunneling of the magnetization. This phenomenon is observed at low temperature in molecules characterized by large spin and large magnetic anisotropy, as is the case for the dodecanuclear manganese(III)–manganese(IV) oxo cluster or the octanuclear iron(III) cluster. More about the properties of such “single‐molecule magnets” can be found in the Review by D. Gatteschi and R. Sessoli on page 268 ff.
Quantum Tunneling of Magnetization and Related Phenomena in Molecular Materials
Authors: Gatteschi Dante , Sessoli Roberta
Published: January 2003

Molecules comprising a large number of coupled paramagnetic centers are attracting much interest because they may show properties which are intermediate between those of simple paramagnets and classical bulk magnets and provide unambiguous evidence of quantum size effects in magnets. To date, two cluster families, usually referred to as Mn12 and Fe8, have been used to test theories. However, it is reasonable to predict that other classes of molecules will be discovered which have similar or superior properties. To do this it is necessary that synthetic chemists have a good understanding of the correlation between the structure and properties of the molecules, for this it is necessary that concepts such as quantum tunneling, quantum coherence, quantum oscillations are understood. The goal of this article is to review the fundamental concepts needed to understand quantum size effects in molecular magnets and to critically report what has been done in the field to date.
Crystallographic report: Bis(N,N‐diethyldithiocarbamato)(2,9‐dimethyl‐1, 10‐phenanthroline)cadmium(II)
Authors: Sing Lai Chian , Tiekink Edward R. T.
Published: January 2003

The mononuclear structure of Cd(S2CNEt2)2(2,9‐Me2‐1,10‐phenanthroline) shows symmetric coordination of the dithiocarbamate ligands and a distorted octahedral geometry for cadmium, defined by an N2S4 donor set, results. Copyright © 2002 John Wiley & Sons, Ltd.
Hybrid Monte Carlo with multidimensional replica exchanges: Conformational equilibria of the hypervariable regions of a llama VHH antibody domain
Authors: Fenwick Michael K. , Escobedo Fernando A.
Published: January 2003

Since the structural repertoire of the hypervariable regions of human antibodies is known to be more restricted than what is implied by sequence variability, a common approach to structural prediction is to use a knowledge‐based (KB) method, such as the canonical structure model (C. Chothia and A. M. Lesk, Journal of Molecular Biology, 1987, Vol. 196, pp. 901–917). However, this model is less successful when applied to camelid heavy chain antibodies. In this study, molecular simulations were used to examine the conformational equilibria of the hypervariable regions (H1, H2, and H3) of a llama heavy chain variable domain, for which KB predictions are poor. Simulations were carried out using both conventional molecular dynamics (MD) and hybrid Monte Carlo with multidimensional replica exchanges (HYMREX). The advantage of the latter method is its ability to selectively target parts of the Hamiltonian that can most readily improve sampling. A novel variant of HYMREX was implemented in which, besides the temperature, torsional interactions and the range of nonbonded interactions were varied. To compare the sampling abilities of MD and this HYMREX scheme, simulations were started from a misfolded conformational state. Overall, MD yielded final conformations more similar to the initial state, implying quasi‐ergodic sampling. In contrast, HYMREX achieved more ergodic sampling, and the majority of conformations that it sampled agreed well with the known crystal structure. The HYMREX simulation results were used to help identify the chief interactions governing the conformational equilibria and to reexamine the key assumptions underlying the KB predictions. The data show that the H1 region exhibited significant conformational freedom, in support of the hypothesis that main‐chain structural variability in this region could play a greater role in antigen binding in camelid antibodies than it does in normal antibodies. Key H1 residues and associated inter‐loop interactions are conjectured to account for the poor KB predictions. © 2002 Wiley Periodicals, Inc. Biopolymers 68:160–177, 2003
Bioprocess considerations for expanded‐bed chromatography of crude canola extract: Sample preparation and adsorbent reuse
Authors: Bai Yun , Glatz Charles E.
Published: January 2003

Compared to the conventional microbial and mammalian systems, transgenic plants produce proteins in a different matrix. This provides opportunities and challenges for downstream processing. In the context of the plant host Brassica napus (canola), this work addresses the bioprocessing challenges of solid fractionation, resin fouling by native plant components (e.g., oil, phenolics, etc.), hydrodynamic stability, and resin reuse for expanded bed adsorption for product capture. Plant tissue processing and subsequent protein extraction typically result in an extract with a high content of solids containing a wide particle‐size distribution. Without removal of larger particles, the column inlet distributor plugged. The larger particles (> 50 μm) were easily removed through centrifugal settling comparable to that attainable with a scroll decanter. The remaining solids did not affect the column performance. Less than 4% of the lipids and phenolics in the fed extract bound to STREAMLINE™ DEAE resin, and this small proportion could be satisfactorily removed using recommended clean‐in‐place (CIP) procedures. Hydrodynamic expansion and adsorption kinetics of the STREAMLINE™ DEAE resin were maintained throughout 10 cycles of reuse, as was the structural integrity of the resin beads. No significant accumulation of N‐rich (e.g., proteins) and C/O‐rich components (e.g., oil and phenolics) occurred over the same period. © 2003 Wiley Periodicals Inc. Biotechnol Bioeng 81: 775–782, 2003.
Modeling of yeast metabolism and process dynamics in batch fermentation
Authors: Sainz Javier , Pizarro Francisco , Pérez‐Correa J. Ricardo , Agosin Eduardo
Published: January 2003

Much is known about yeast metabolism and the kinetics of industrial batch fermentation processes. In this study, however, we provide the first tool to evaluate the dynamic interaction that exists between them. A stoichiometric model, using wine fermentation as a case study, was constructed to simulate batch cultures of Saccharomyces cerevisiae. Five differential equations describe the evolution of the main metabolites and biomass in the fermentation tank, while a set of underdetermined linear algebraic equations models the pseudo‐steady‐state microbial metabolism. Specific links between process variables and the reaction rates of metabolic pathways represent microorganism adaptation to environmental changes in the culture. Adaptation requirements to changes in the environment, optimal growth, and homeostasis were set as the physiological objectives. A linear programming routine was used to define optimal metabolic mass flux distribution at each instant throughout the process. The kinetics of the process arise from the dynamic interaction between the environment and metabolic flux distribution. The model assessed the effect of nitrogen starvation and ethanol toxicity in wine fermentation and it was able to simulate fermentation profiles qualitatively, while experimental fermentation yields were reproduced successfully as well. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 818–828, 2003.
Combined transcriptome and proteome analysis of Escherichia coli during high cell density culture
Authors: Yoon Sung Ho , Han Mee‐Jung , Lee Sang Yup , Jeong Ki Jun , Yoo Jong‐Shin
Published: January 2003

Combined transcriptome and proteome analysis was carried out to understand metabolic and physiological changes of Escherichia coli during the high cell density cultivation (HCDC). The expression of genes of TCA cycle enzymes, NADH dehydrogenase and ATPase, was up‐regulated during the exponential fed‐batch period and was down‐regulated afterward. However, expression of most of the genes involved in glycolysis and pentose phosphate pathway was up‐regulated at the stationary phase. The expression of most of amino acid biosynthesis genes was down‐regulated as cell density increased, which seems to be the major reason for the reduced specific productivity of recombinant proteins during HCDC. The expression of chaperone genes increased with cell density, suggesting that the high cell density condition itself can be stressful to the cells. Severe competition for oxygen at high cell density seemed to make cells use cytochrome bd, which is less efficient but has a high oxygen affinity than cytochrome bo3. Population cell density itself strongly affected the expression of porin protein genes, especially ompF, and hence the permeability of the outer membrane. Expression of phosphate starvation genes was most strongly up‐regulated toward the end of cultivation. It was also found that σE (rpoE) plays a more important role than σS (rpoS) at the stationary phase of HCDC. These findings should be invaluable in designing metabolic engineering and fermentation strategies for the production of recombinant proteins and metabolites by HCDC of E. coli. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 753–767, 2003.
Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat
Authors: Kishi Toshiro , Aschkenasi Carl J. , Lee Charlotte E. , Mountjoy Kathleen G. , Saper Clifford B. , Elmquist Joel K.
Published: January 2003

The melanocortin 4 receptor (MC4‐R) plays a pivotal role in maintaining energy homeostasis in rodents and humans. For example, MC4‐R deletion or mutation results in obesity, hyperphagia, and insulin resistance. Additionally, subsets of leptin‐induced autonomic responses can be blocked by melanocortin receptor antagonism, suggesting that MC4‐R–expressing neurons are downstream targets of leptin. However, the critical autonomic control sites expressing MC4‐Rs are still unclear. In the present study, we systematically examined the distribution of MC4‐R mRNA in the adult rat central nervous system, including the spinal cord, by using in situ hybridization histochemistry (ISHH) with a novel cRNA probe. Autonomic control sites expressing MC4‐R mRNA in the hypothalamus included the anteroventral periventricular, ventromedial preoptic, median preoptic, paraventricular, dorsomedial, and arcuate nuclei. The subfornical organ, dorsal hypothalamic, perifornical, and posterior hypothalamic areas were also observed to express MC4‐R mRNA. Within extrahypothalamic autonomic control sites, MC4‐R–specific hybridization was evident in the infralimbic and insular cortices, bed nucleus of the stria terminalis, central nucleus of the amygdala, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus (DMV), and intermediolateral nucleus of the spinal cord (IML). By using dual‐label ISHH, we confirmed that the cells expressing MC4‐R mRNA in the IML and DMV were autonomic preganglionic neurons as cells in both sites coexpressed choline acetyltransferase mRNA. The distribution of MC4‐R mRNA is consistent with the proposed roles of central melanocortin systems in feeding and autonomic regulation. J. Comp. Neurol. 457:213–235, 2003. © 2003 Wiley‐Liss, Inc.
Epidermal reinnervation after intracutaneous axotomy in man
Authors: Rajan Bindu , Polydefkis Michael , Hauer Peter , Griffin John W. , McArthur Justin C.
Published: January 2003

Two distinct patterns of reinnervation occur after injury to the cutaneous nerves: regenerative growth of the injured nerve and “collateral sprouting” of neighboring intact nerves. We describe two complementary models of regrowth of transected small sensory fibers in human skin. The “incision” model uses a circular incision that transects the subepidermal plexus, resulting in Wallerian degeneration of the nerve fibers that enter the incised cylinder, leaving a defined zone of denervated dermis and epidermis. The “excision” model utilizes an identical incision, followed by removal of the incised cylinder of skin, leaving a denervated area in which Schwann cells are absent. In the incision model, the earliest reinervation of denervated epidermis occurred by collateral sprouting from the terminals of epidermal axons from just outside the incision line. These axon terminals extended horizontally across the incision line and through the superficial layers of the epidermis, beneath the stratum corneum. By 13 days, numerous regenerating axons appeared in the deeper dermis derived from transected axons. These regenerating axons grew toward and ultimately into the epidermis, so that epidermal axonal density had normalized by 30–75 days. The invasion of these axons was associated with regression of the horizontally growing collateral sprouts. In the excision model, new fibers arose by terminal elongation of the epidermal axons outside the incision line, as in the incision model, and especially by collateral branching of epidermal fibers at the incision margins. These collaterals reached the epidermal surface of the basal lamina at the dermal–epidermal junction and then grew slowly toward the center of the denervated circle. In contrast to the incision model, however, complete reinnervation was not achieved even after 23 months. These models can be used to study reinnervation of denervated skin in man in different injury models and have relevance for exploring the stimuli for axonal growth and remodeling. J. Comp. Neurol. 457:24–36, 2003. © 2003 Wiley‐Liss, Inc.
Tectothalamic visual projections in turtles: Their cells of origin revealed by tracing methods
Authors: Belekhova Margarita , Kenigfest Natalia , Rio Jean‐Paul , Repérant Jacques , Ward Roger , Vesselkin Nikolai , Karamian Olga
Published: January 2003

In two species of turtle (Emys orbicularis and Testudo horsfieldi), retrograde and anterograde tracer techniques were used to study projections from the optic tectum to the nucleus rotundus (Rot) and to the dorsal lateral geniculate nucleus (GLd). The ipsilateral Rot received the most massive tectal projections, stemming from numerous neurons located in the stratum griseum centrale (SGC). These neurons varied in size and shape, many of them having a wide zone of dendritic arborization within both the (SGC) and the stratum griseum et fibrosum superficiale (SGFS). Projections from the tectum to the GLd were ipsilateral, were extremely scarce, and arose from a small number of neurons of various shapes situated in the SGFS; these cells were, as a rule, smaller than those projecting to the Rot. For the most part, these neurons were radially oriented, with rather restricted dendritic arborizations in the most superficial sublayers of the SGFS; smaller numbers of projection neurons were horizontally oriented, with long dendrites branching throughout the layer. Some neurons located in the stratum griseum periventriculare (SGP) projected to both the Rot and the GLd. Most of these neurons had dendritic arborizations within the retinorecipient zone of the SGFS. We were unable to rule out the possibility that some cells projecting to the GLd were situated in the SGC. Both the GLd and the main body of the Rot did not contain neurons projecting to the optic tectum. Thalamic neurons projecting to the tectum were observed in the ventral lateral geniculate nucleus, the intergeniculate leaflet and the interstitial nuclei of the tectothalamic tract, and the nucleus of the decussatio supraoptica ventralis. The question of whether variation in the laminar organization of the tectorotundal and tectogeniculate projection neurons in reptiles, birds, and mammals may be related to different degrees of differentiation of the tectal layers is discussed. J. Comp. Neurol. 457:37–56, 2003. © 2003 Wiley‐Liss, Inc.
Changes in mouse barrel synapses consequent to sensory deprivation from birth
Authors: Sadaka Yair , Weinfeld Elizabeth , Lev Dmitri L. , White Edward L.
Published: January 2003

Neonatal sensory deprivation induced by whisker trimming affects significantly the functional organization of receptive fields in adult barrel cortex. In this study, the effects of deprivation on thalamocortical synapses and on asymmetrical and symmetrical synapses not of thalamic origin were examined. Thalamocortical synapses were labeled by lesion‐induced degeneration in adult (postnatal day 60) mice subjected to whisker trimming from birth, other synaptic types were unlabeled. Brains were processed for electron microscopy, and numerical densities of synapses were evaluated by using stereologic approaches for whisker trimmed vs. control animals. Results demonstrated no change in nonthalamic, asymmetrical synapses; however, a decrease of 52% in the numerical density of symmetrical synapses (46.3 vs. 88.5 million per mm3; Z = −2.121; P < 0.05) and a decrease of 43% in the numerical density of thalamocortical synapses (57.5 vs. 102.33 million per mm3; Z = −2.121; P < 0.05) were observed after deprivation. Thus, experience‐dependent plasticity of receptive fields in barrel cortex involves directly axons of both extrinsic and intracortical origin. The proportion of thalamocortical axospinous to axodendritic synapses was the same in control vs. deprived animals: in each instance, 80% of the synapses were axospinous (Z = 0.85; P = 0.2). These results suggest that neither excitatory neurons, whose thalamocortical synapses are primarily axospinous, nor inhibitory neurons, whose thalamocortical synapses are mainly axodendritic (White [1989] Cortical Circuits. Synaptic Organization of the Cerebral Cortex; Structure, Function, and Theory. 1989; Boston: Birkhauser), are affected preferentially by the deprivation‐associated decrease in thalamocortical synapses. J. Comp. Neurol. 457:75–86, 2003. © 2003 Wiley‐Liss, Inc.
The relationship between hodological and cytoarchitectonic organization in the vestibular complex of the 11‐day chicken embryo
Authors: Díaz Carmen , Glover Joel C. , Puelles Luis , Bjaalie Jan G.
Published: January 2003

To understand the relationship between structure and function in specific brain regions, it is necessary to ascertain which anatomical features are physiologically relevant. Physiological studies of brain function traditionally have been set in the context of anatomical features based on cytoarchitectonics and myeloarchitectonics, but the relationship between structure and function in this context can be complex. Alternative schemes of anatomical organization, such as that based on hodology (the mapping of projections) may provide greater insight. Here, we make a direct comparison of the hodological and the cytoarchitectonic organization of the vestibular complex in the mid‐term chicken embryo, using retrograde tracing and three‐dimensional reconstruction. In one set of experiments, vestibulospinal and vestibulo‐ocular neuron groups were selectively labeled with biotin dextran‐amines and aligned with the cytoarchitectonically defined vestibular nuclei in alternating sections that were then combined into intercalated three‐dimensional models. This allowed a semiquantitative analysis of the apportionment of individual hodological groups among cytoarchitectonic nuclei. In another set of experiments, vestibulospinal and vestibulo‐ocular neuron groups were labeled differentially with fluorescent dextran‐amines, three‐dimensionally reconstructed, and subjected to a quantitative analysis of spatial overlap. Our results provide the first three‐dimensional representation and quantitative analysis of the hodological compartmentalization of the vestibular complex (the “hodological mosaic”). They also show directly how each hodologically defined neuron group relates to the conventional vestibular nuclei, underscoring the fact that the units of the hodological mosaic do not bear a one‐to‐one correspondence to the cytoarchitectonic nuclear divisions. Some hodologically defined groups are localized to restricted portions of a nucleus, whereas others overlap multiple nuclei. Thus, hodology and cytoarchitectonic features appear to be separately regulated in the vestibular complex of the chicken embryo, possibly through different sets of positional specification mechanisms. The three‐dimensional representations we present here provide a foundation for integrating anatomical, physiological, developmental, and evolutionary studies of the vestibular system. J. Comp. Neurol. 457:87–105, 2003. © 2003 Wiley‐Liss, Inc.
Progressive recovery of learning during regeneration of a single synapse in the medicinal leech
Authors: Burrell Brian D. , Sahley Christie L. , Muller Kenneth J.
Published: January 2003

The leech escape reflex—shortening of the body—can change with nonassociative conditioning, including sensitization, habituation, and dishabituation. Capacity for sensitization, which is an enhancement of the reflex, is lost when a single S‐interneuron is ablated, but the reflex response itself remains. In the present experiments, the S‐interneuron's axon in the living leech was filled with 6‐carboxyfluorescein (6‐CF) dye and cut with an argon laser microbeam (λ = 488 nm). In contrast to sham‐operated animals, axotomized preparations did not sensitize, reflecting the key role of the S‐cell. By 2 weeks or more, S‐cell axons had regenerated and reestablished synapses at their usual locations with neighboring S‐cells. By 4 weeks, this restored the ability to sensitize to a level indistinguishable from that of controls, but an intermediate state of recovery was seen from 2–3 weeks after injury—a period not previously examined. The small capacity for sensitization among newly regenerated preparations was significantly lower than in sham controls but appeared higher than in animals whose cut S‐cell axon had not regenerated its synapse. The results confirm the crucial role of the S‐cell in sensitization. Moreover, full sensitization does not occur immediately upon synapse regeneration. J. Comp. Neurol. 457:67–74, 2003. © 2003 Wiley‐Liss, Inc.
Reevaluation of the primary motor cortex connections with the thalamus in primates
Authors: Kultas‐Ilinsky Kristy , Sivan‐Loukianova Elena , Ilinsky Igor A.
Published: January 2003

Six injections (∼1 mm in diameter) of biotinylated dextran amine (BDA) were placed in different locations of the primary motor cortex of the rhesus monkey. Anterograde and retrograde labeling patterns in the thalamus were charted and individual labeled axons traced in continuous serial sections. Both anterograde and retrograde labeling in the thalamus was extensive, spanning several millimeters mediolaterally and including ventral lateral, ventral anterior, centromedian, and centrolateral nuclei. Paracentral, mediodorsal, lateral posterior, and medial pulvinar nuclei were also labeled. Two basic types of corticothalamic axons were identified: small to medium‐width, type 1 axons that formed large terminal fields with small boutons, and thick, type 2 axons that formed small terminal fields with large boutons. Within each group, subtypes were identified based on specific features of the axons and terminals: two subtypes of type 1 axons and four subtypes of type 2 axons. The results revealed multiple modes of corticothalamic connectivity: sparsely distributed type 1 axons, dense plexuses of type 1 axons, type 2 axon terminal fields either singly or in clusters, and mixed plexuses of type 1 and type 2 axons. Only some cells in the plexuses were retrogradely labeled; some plexuses did not contain any labeled neurons, and many retrogradely labeled neurons were in the regions devoid of anterograde labeling. These connectivity patterns differed between thalamic nuclei. The results revealed much more complex relationships between M1 and thalamus than were previously thought to exist. It is suggested that this connectivity is neither of exclusively a feedback nature nor perfectly reciprocal but is subserved by a multitude of channels, most likely originating from different populations of cortical neurons, and feeding into a variety of functionally different neuronal networks, with each processing specific information. J. Comp. Neurol. 457:133–158, 2003. © 2003 Wiley‐Liss, Inc.
Somatosensory cortex of prosimian Galagos: Physiological recording, cytoarchitecture, and corticocortical connections of anterior parietal cortex and cortex of the lateral sulcus
Authors: Wu Carolyn W.‐H. , Kaas Jon H.
Published: January 2003

Compared with our growing understanding of the organization of somatosensory cortex in monkeys, little is known about prosimian primates, a major branch of primate evolution that diverged from anthropoid primates some 60 million years ago. Here we describe extensive results obtained from an African prosimian, Galago garnetti. Microelectrodes were used to record from large numbers of cortical sites in order to reveal regions of responsiveness to cutaneous stimuli and patterns of somatotopic organization. Injections of one to several distinguishable tracers were placed at physiologically identified sites in four different cortical areas to label corticortical connections. Both types of results were related to cortical architecture. Three systematic representations of cutaneous receptors were revealed by the microelectrode recordings, S1 proper or area 3b, S2, and the parietal ventral area (PV), as described in monkeys. Strips of cortex rostral (presumptive area 3a) and caudal (presumptive area 1–2) to area 3b responded poorly to tactile stimuli in anesthetized galagos, but connection patterns with area 3b indicated that parallel somatosensory representations exist in both of these regions. Area 3b also interconnected somatotopically with areas S2 and PV. Areas S2 and PV had connections with areas 3a, 3b, 1–2, each other, other regions of the lateral sulcus, motor cortex (M1), cingulate cortex, frontal cortex, orbital cortex, and inferior parietal cortex. Connection patterns and recordings provided evidence for several additional fields in the lateral sulcus, including a retroinsular area (Ri), a parietal rostral area (PR), and a ventral somatosensory area (VS). Galagos appear to have retained an ancestoral preprimate arrangement of five basic areas (S1 proper, 3a, 1–2, S2, and PV). Some of the additional areas suggested for lateral parietal cortex may be primate specializations. J. Comp. Neurol. 457:263–292, 2003. © 2003 Wiley‐Liss, Inc.
Differential cholinergic activation of G proteins in rat and mouse brainstem: Relevance for sleep and nociception
Authors: Demarco George J. , Baghdoyan Helen A. , Lydic Ralph
Published: January 2003

Murine models are increasingly used for investigations of sleep, yet no previous studies have characterized cholinergic activation of guanine nucleotide binding proteins (G proteins) in mouse brainstem nuclei known to regulate sleep. This study used in vitro [35S]guanylyl‐5′‐O‐(γ‐thio)‐triphosphate ([35S]GTPγS) autoradiography to test the hypothesis that muscarinic cholinergic receptors activate G proteins in C57BL/6J (B6) mouse brainstem. The nuclei studied are homologous to those known in rat and cat to modulate sleep and nociception. In B6 mouse, carbachol significantly increased specific binding of [35S]GTPγS in the pontine reticular nucleus, caudal part (79%); pontine reticular nucleus, oral part (131%); laterodorsal tegmental nucleus (56%); pedunculopontine tegmental nucleus (86%); dorsal raphe nucleus (53%); dorsal medial periaqueductal gray (54%); and ventrolateral periaqueductal gray (52%) when compared with basal binding. Carbachol‐induced G protein activation was concentration‐dependent and blocked by atropine, demonstrating mediation by muscarinic receptors. G protein activation by carbachol was heterogeneous across B6 mouse brainstem nuclei. Comparison of [35S]GTPγS binding between mouse and rat revealed different magnitudes of G protein activation in the pontine reticular formation. In the same pontine reticular formation area of B6 mouse where in vitro treatment with carbachol activates G proteins, in vivo microinjection of cholinomimetics causes a rapid eye movement sleep‐like state. These data provide the first direct measurement of muscarinic receptor‐activated G proteins in B6 mouse brainstem nuclei known in other species to regulate sleep. J. Comp. Neurol. 457:175–184, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of keratin 8‐containing cell clusters in mouse embryonic tongue: Evidence for a prepattern for taste bud development
Authors: Mbiene Joseph‐Pascal , Roberts John David
Published: January 2003

The initiation of the morphogenesis of gustatory papillae is independent of innervation. To address the question of whether taste bud formation is associated with gustatory papilla morphogenesis, we examined developing tongues in mouse embryos from embryonic day 11 to birth. Despite the smooth morphological appearance of the lingual dorsal surface at 13 days of gestation, we observed embryonic taste bud primordia as discrete collections of cytokeratin 8‐positive and elongated cells in epithelial placodes in the anterior tongue. In subsequent stages until birth, cytokeratin 8 continues to be expressed in embryonic taste buds distributed in punctuate patterns at regular intervals along rows that are symmetrically located on both sides of the median sulcus in the dorsal anterior developing tongue. Embryonic taste buds were observed in the developing circumvallate papillae from 15.5 days of gestation until birth. The dorsal epithelium of the anterior tongue is not innervated when embryonic taste buds first occur. The increased numbers of embryonic taste buds in developing fungiform papillae until birth are not correlated with the neural invasion of the epithelium. Thus, taste buds occur prenatally more likely independently of the innervation. J. Comp. Neurol. 457:111–122, 2003. © 2003 Wiley‐Liss, Inc.
Inner S‐cone bipolar cells provide all of the central elements for S cones in macaque retina
Authors: Herr Steve , Klug Karl , Sterling Peter , Schein Stan
Published: January 2003

Synaptic terminals of cones (pedicles) are presynaptic to numerous processes that arise from the dendrites of many types of bipolar cell. One kind of process, a central element, reaches deeply into invaginations of the cone pedicle just below an active zone associated with a synaptic ribbon. By reconstruction from serial electron micrographs, we show that L‐ and M‐cone pedicles in macaque fovea are presynaptic to ∼20 central elements that arise from two types of inner (invaginating) bipolar cell, midget and diffuse. In contrast, S‐cone pedicles, with more synaptic ribbons, active zones/ribbon, and central elements/active zone, are presynaptic to ∼33 central elements. Moreover, all of these arise from one type of bipolar cell, previously described by others, here termed an inner S‐cone bipolar cell. Each provides ∼16 central elements. Thirty‐three is twice 16; correspondingly, these bipolar cells are twice as numerous as S cones. (Specifically, each S cone is presynaptic to four inner S‐cone bipolar cells; in turn, each bipolar cell provides central elements to two S cones.) These bipolar cells are presynaptic to an equal number of small‐field bistratified ganglion cells, giving cell numbers in 2G:2B:1S ratios. Each ganglion cell receives input from two or more inner S‐cone bipolar cells and thereby collects signals from three or more S cones. This convergence, along with chromatic aberration of short‐wavelength light, suggests that S‐cone contributions to this ganglion cell's coextensive blue‐ON/yellow‐OFF receptive field are larger than opponent L/M‐cone contributions via outer diffuse bipolar cells and that opponent L/M‐cone signals are conveyed mainly by inner S‐cone bipolar cells. J. Comp. Neurol. 457:185–201, 2003. © 2003 Wiley‐Liss, Inc.
Developmental changes in the expression of chemokine receptor CCR1 in the rat cerebellum
Authors: Cowell Rita Marie , Silverstein Faye Sarah
Published: January 2003

Chemokines are small, soluble proteins that regulate leukocyte migration, adhesion, and proliferation. Recent evidence suggests that chemokine receptors are expressed in the central nervous system and that their functions extend beyond their roles in inflammation. Specific chemokines and their receptors are implicated in cerebellar development. In this study, we evaluated the expression of β‐chemokine receptor CCR1 in the immature and adult rat cerebellum and report striking developmental changes in CCR1 expression. Reverse transcriptase polymerase chain reaction assays of cerebellum revealed moderate increases in CCR1 mRNA expression from postnatal day (P) 3 to adulthood. Light and confocal microscopy were used to evaluate developmental changes in the neuroanatomical and cell‐specific distribution of CCR1 immunoreactivity. CCR1 immunoreactivity was detected as early as P3 and peaked between P7 and P21. The predominant CCR1‐immunoreactive neuronal cell types included granule cells of the internal granular layer, Purkinje cells, Golgi cells, and molecular layer interneurons; Bergmann glia, astrocytes, and resting microglia also expressed CCR1. In contrast, granule cells in the external germinal layer, descending granule cells, and activated microglia rarely expressed CCR1. We also evaluated the expression of the CCR1 ligand macrophage inflammatory protein‐1α (MIP‐1α/CCL3). Two cell populations expressed MIP‐1α: physiologically activated microglia in white matter (P7–P14) and Purkinje cells (P7–adult). MIP‐1α‐positive cells were frequently located near the processes and cell bodies of CCR1‐immunoreactive cells, during times of neuronal and glial maturation (second and third postnatal weeks). These findings provide support for the hypothesis that CCR1 plays a role in postnatal cerebellar development. J. Comp. Neurol. 457:7–23, 2003. © 2003 Wiley‐Liss, Inc.