bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetics of Drosophila transgenics
Authors: Roman Gregg
Published: October 2004

In Drosophila, the genetic approach is still the method of choice for answering fundamental questions on cell biology, signal transduction, development, physiology and behavior. In this approach, a gene's function is ascertained by altering either the amount or quality of the gene product, and then observing the consequences. The genetic approach is itself polymorphous, encompassing new and more complex techniques that typically employ the growing collections of transgenes. The keystone of these modern Drosophila transgenic techniques has been the Gal4 binary system. Recently, several new techniques have modified this binary system to offer greater control over the timing, tissue specificity and magnitude of gene expression. Additionally, the advances in post‐transcriptional gene silencing, or RNAi, have greatly expanded the ability to knockdown almost any gene's function. Regardless of the growing experimental intricacy, the application of these advances to modify gene activity still obeys the fundamental principles of genetic analysis. Several of these transgenic techniques, which offer more precise control over a gene's activity, will be reviewed here with a discussion on how they may be used for determining a gene's function. BioEssays 26:1243–1253, 2004. © 2004 Wiley Periodicals, Inc.
Chromosome rearrangements resulting from telomere dysfunction and their role in cancer
Authors: Murnane John P. , Sabatier Laure
Published: October 2004

Telomeres play a vital role in protecting the ends of chromosomes and preventing chromosome fusion. The failure of cancer cells to properly maintain telomeres can be an important source of the chromosome instability involved in cancer cell progression. Telomere loss results in sister chromatid fusion and prolonged breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and large deletions. These B/F/B cycles end primarily when the unstable chromosome acquires a new telomere by translocation of the ends of other chromosomes. Many of these translocations are nonreciprocal, resulting in the loss of the telomere from the donor chromosome, providing a mechanism for transfer of instability from one chromosome to another until a chromosome acquires a telomere by a mechanism other than nonreciprocal translocation. B/F/B cycles can also result in other forms of chromosome rearrangements, including double‐minute chromosomes and large duplications. Thus, the loss of a single telomere can result in instability in multiple chromosomes, and generate many of the types of rearrangements commonly associated with human cancer. BioEssays 26:1164–1174, 2004. © 2004 Wiley Periodicals, Inc.
An intracellular actin motor in bacteria?
Authors: Graumann Peter L. , Defeu Soufo Hervé Joël
Published: October 2004

Actin performs structural as well as motor‐like functions in eukaryotic cells. Orthologues of actin have also been identified in bacteria, where they perform an essential function during cell growth. Bacterial actins are implicated in the maintenance of rod‐shaped cell morphology, and appear to form a cytoskeletal structure, localising as helical filaments underneath the cell membrane. Recently, a plasmid‐borne actin orthologue has been shown to perform a mitotic‐like function during segregation of a plasmid, and chromosomally encoded actin proteins were found to play an important role in chromosome segregation. Based on the findings that actin filaments are dynamic structures in two bacterial species, we propose that actins perform motor functions rather than a purely structural role in bacteria. We suggest that an intracellular motor exists in bacteria that could be derived from an ancestral actin motor that was present in cells early in evolution. BioEssays 26:1209–1216, 2004. © 2004 Wiley Periodicals, Inc.
How consistent are expression chip platforms?
Authors: Jordan Bertrand R.
Published: October 2004

DNA arrays are now widely used in academia and industry, and expression profiling is recognised as a major tool for basic research as well as for drug development. It is also likely, in the near future, that DNA arrays will be used in clinical laboratories for diagnostic and prognostic purposes. Since several types of arrays are being used, the coherence of results obtained using these diverse platforms becomes an important issue: to what extent can data obtained in different laboratories and with different equipment be combined? Several recent papers address this issue and demonstrate that the expected agreement is not necessarily found. Consistent results can be obtained, but this requires careful identification of the genes assessed by the arrays, and scrupulous adherence to strict experimental procedures. BioEssays 26:1236–1242, 2004. © 2004 Wiley Periodicals, Inc.
Repair of exocyclic DNA adducts: rings of complexity
Authors: Hang Bo
Published: October 2004

Exocyclic DNA adducts are mutagenic lesions that can be formed by both exogenous and endogenous mutagens/carcinogens. These adducts are structurally analogs but can differ in certain features such as ring size, conjugation, planarity and substitution. Although the information on the biological role of the repair activities for these adducts is largely unknown, considerable progress has been made on their reaction mechanisms, substrate specificities and kinetic properties that are affected by adduct structures. At least four different mechanisms appear to have evolved for the removal of specific exocyclic adducts. These include base excision repair, nucleotide excision repair, mismatch repair, and AP endonuclease‐mediated repair. This overview highlights the recent progress in such areas with emphasis on structure–activity relationships. It is also apparent that more information is needed for a better understanding of the biological and structural implications of exocyclic adducts and their repair. BioEssays 26:1195–1208, 2004. © 2004 Wiley Periodicals, Inc.
What the papers say: Where is the somatic mutation that causes aging?
Authors: Driver Christopher
Published: October 2004

It has been proposed that somatic mutations make major contributions to aging. The first paper, based on a gene knock‐in mouse, supports a contributory role for mutation in mtDNA1 in aging, but does not support a damaged‐mtDNA‐producing‐more‐damaged‐mtDNA hypothesis.1 The second paper2 indicates some GC‐rich sequences in the nuclear DNA are more sensitive to oxidative damage than mtDNA. As a result, key genes involved in brain function and mitochondrial function are progressively inactivated with age. Failure in these nucleus‐encoded mitochondrial genes may be a primary reason for mitochondrial failure in old age. BioEssays 26:1160–1163, 2004. © 2004 Wiley Periodicals, Inc.
Exploring the multiple facets of the meiotic recombinase Dmc1
Authors: Sauvageau Synthia , Ploquin Mickaël , Masson Jean‐Yves
Published: October 2004

Meiotic recombination in eukaryotic cells requires two homologs of E. coli RecA protein, Rad51 and Dmc1. Until recently, the role of Dmc1 in meiotic recombination was mostly attributed to genetic studies as purified Dmc1 was found to be a much weaker recombinase than Rad51 in the test tube. Now, Sehorn and colleagues1 have reported that, like Rad51, human Dmc1 is an efficient recombinase in vitro. Dmc1 forms helical nucleoprotein filaments—the signature of classical recombinases such as Rad51. These observations reveal a high level of similitude between the Dmc1 and the Rad51 family of recombination enzymes in higher eukaryotes. BioEssays 26:1151–1155, 2004. © 2004 Wiley Periodicals, Inc.
Generalized Poland–Scheraga model for DNA hybridization
Authors: Garel Thomas , Orland Henri
Published: October 2004

The Poland–Scheraga (PS) model for the helix–coil transition of DNA considers the statistical mechanics of the binding (or hybridization) of two complementary strands of DNA of equal length, with the restriction that only bases with the same index along the strands are allowed to bind. In this article, we extend this model by relaxing these constraints: We propose a generalization of the PS model that allows for the binding of two strands of unequal lengths N1 and N2 with unrelated sequences. We study in particular (i) the effect of mismatches on the hybridization of complementary strands, (ii) the hybridization of noncomplementary strands (as resulting from point mutations) of unequal lengths N1 and N2. The use of a Fixman–Freire scheme scales down the computational complexity of our algorithm from O(NN) to O(N1N2). The simulation of complementary strands of a few kilo base pairs yields results almost identical to the PS model. For short strands of equal or unequal lengths, the binding displays a strong sensitivity to mutations. This model may be relevant to the experimental protocol in DNA microarrays, and more generally to the molecular recognition of DNA fragments. It also provides a physical implementation of sequence alignments. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Polypeptide conjugates comprising a β‐amyloid plaque‐specific epitope as new vaccine structures against Alzheimer's disease
Authors: Manea Marilena , Mezö Gábor , Hudecz Ferenc , Przybylski Michael
Published: October 2004

Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for possible vaccination to the treatment of Alzheimer's disease (AD). Based on the identification of Aβ(4–10) (FRHDSGY) as the predominant B‐cell epitope recognized by therapeutically active antisera from transgenic AD mice, branched polypeptide conjugates with this epitope peptide were synthesized and characterized. In order to produce immunogenic constructs, the Aβ(4–10) epitope alone or together with a promiscuous T‐helper cell epitope peptide (FFLLTRILTIPQSLD) were attached via thioether linkage to different branched chain polymeric polypeptides with Ser or Glu in the side chains. A single peptide containing both an Aβ(4–10) and T‐helper cell epitope, joined by a dipeptide Cys–Acp spacer, was also attached through the thiol function to chloroacetylated poly[Lys(Seri–DL–Alax)] (SAK). Comparative binding studies of the conjugates with a monoclonal antibody against the β‐amyloid(1–17) peptide in mice were performed by direct ELISA. The conformational preferences of carriers and conjugates in water and in a 9:1 triflouroethanol:water mixture (v/v) was analyzed by CD spectroscopy. Experimental data showed that the chemical nature of the carrier macromolecule, and the attachment site of the epitope to the carrier, have significant effects on antibody recognition, but have no marked influence on the solution conformation of the conjugates. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004
Total synthesis in solution of alamethicin F50/5 by an easily tunable segment condensation approach
Authors: Peggion Cristina , Coin Irene , Toniolo Claudio
Published: October 2004

A total synthesis in solution of the 19‐mer peptide component F50/5 of alamethicin, the most extensively investigated among the channel‐former peptaibol antibiotics, is reported. Three peptide segments (A, B, C) were prepared and assembled, followed by incorporation of the acetylated N‐terminal amino acid. The synthetic modules B and C are characterized by three Glu(OMe) residues (at positions 7, 18, and 19) that, after completion of the synthesis, were reacted with ammonia to provide alamethicin F50/5. By use of this general strategy, we also prepared the [Gln7, Glu(OMe)18,19] alamethicin F50/5 analogue. The purity and conformation of the final products were assessed by chromatographic, spectrometric, and spectroscopic techniques. This tunable segment condensation approach will pave the way for an easy synthesis of alamethicin analogues bearing amino acid residues with desired side‐chain probes even at the N‐terminus and in internal positions of the sequence. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004
Synthesis and in vitro Antineoplastic Evaluation of Certain 16‐(4‐Substituted Benzylidene) Derivatives of Androst‐5‐ene
Authors: Dubey Sonal , Piplani Poonam , Jindal† Dharam Paul
Published: October 2004

In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antiproliferative activity against cancer cells, we synthesized certain 16‐[4‐(NO2, CN, and i‐Pr)substituted]benzylidene derivatives of androst‐5‐ene, 7–25, with pyrrolidino functionality in the 3β‐position of the steroid nucleus, i.e., 13–18 and 25. The selected compounds were examined for their cytotoxicity against a panel of three human cancer cell lines at the National Cancer Institute (NCI), Bethesda, USA. The results presented herein provide experimental evidence that compounds 7, 9, 10, 12, 16, and 19–21 induced apoptosis in human cancer cells.
Synthesis of Spiro[5.4]decenones and Their Transformation into Bicyclo[4.4]deca‐1,4‐dien‐3‐ones by Domino “Elimination– Double‐Wagner–Meerwein‐Rearrangement” Reactions
Authors: Bose Gopal , Ullah Ehsan , Langer Peter
Published: October 2004

The [3+3] cyclization of 1,3‐bis‐silyl enol ethers with 1,1‐diacylcyclopentanes allows a convenient synthesis of spiro[5.4]decenones. Treatment of these compounds with trifluoroacetic acid (TFA) afforded a great variety of bicyclo[4.4.0]deca‐1,4‐dien‐3‐ones containing an angular alkyl group. This core structure occurs in a number of pharmacologically relevant natural products.
MRI heterogeneity of articular cartilage in strong magnetic fields: Dependence on proteoglycan content
Authors: Othman Shadi F. , Williams James M. , Sumner Dale R. , Magin Richard L.
Published: October 2004

Articular cartilage is a thin heterogeneous tissue (typical thickness of less than 2 mm) composed of collagen, proteoglycan, and water that coats skeletal joint surfaces. Its physical and chemical integrity are essential for maintaining normal joint articulation. MR imaging techniques are being developed to visualize articular cartilage for the purpose of assessing changes in its structure that occur with age and the onset of joint disease. Emerging high‐field MR systems (greater than 4 T) have a higher signal‐to‐noise ratio, which can be used to improve the spatial resolution for imaging articular cartilage beyond that available in most clinical systems. In this study, we examined the effect of changing the proteoglycan content of articular cartilage on high‐resolution (40 × 40 × 100 μm) T1‐ and T2‐weighted images acquired at 11.74 T (500 MHz for protons). Susceptibility artifacts were observed near the cartilage‐bone interface that were verified by separating the cartilage from the bone. MR image heterogeneity of articular cartilage was observed as a function of depth and in the transverse directions of the sample. Enzymatic depletion of cartilage proteoglycan demonstrated that the MR image heterogeneity is due in part to variation of the proteoglycan content in different regions of the cartilage. The apparent diffusion coefficient (ADC) was measured as a function of depth in the cartilage. The ADC varied from the subchondral bone to the articular surface for both normal and digested cartilage. In addition, the ADC increased by 20% after 6 hours of enzymatic digestion of proteoglycan. These results suggest a role for high‐field MRI of articular cartilage in the management and staging of osteoarthritis and other joint diseases. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 23B: 33–43, 2004
Design and construction of a dipolar Halbach array with a homogeneous field from identical bar magnets: NMR Mandhalas
Authors: Raich H. , Blümler P.
Published: October 2004

Magnets of the Halbach layout are interesting for the use in mobile NMR/MRI devices. Therefore, the ideal Halbach magnet was iterated using identical bar magnets, which are positioned and oriented based on analytical equations. These configurations were simulated with two‐dimensional finite‐element methods. Performance factors were defined to relate field strength with homogeneity and mass. A geometry of 16 magnets provided a good compromise between performance and special requirements for the desired use to store hyperpolarized xenon. The construction of such a magnet required the design of dedicated support frames and procedures to mount them. The field strength and homogeneity in the finished magnet were measured by a Hall probe and agreed well with the simulations. The calculation and construction are described in detail and together with the tabled field values for n magnets with n ≤ 80 may prove helpful for building similar devices, which were named NMR Mandhalas (Magnet Arrangements for Novel Discrete Halbach Layout). © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 23B: 16–25, 2004
RF flux guides for excitation and reception in 31P spectroscopic and imaging experiments at 2 Tesla
Authors: Behr Volker C. , Haase Axel , Jakob Peter M.
Published: October 2004

Radio frequency (RF) flux guides consist of microstructured materials that are able to transport magnetic flux even within strong static magnetic fields, such as those found inside a superconducting magnet used for nuclear magnetic resonance (NMR) experiments. This offers the possibility to examine samples whose geometries impose restrictions on the direct accessibility of the sample. In these cases, flux guides can transmit the magnetic flux from a remote resonator into the sample, thereby occupying less space and allowing a wider range of coil designs. An RF flux guide is presented in 31P spectroscopic and imaging experiments on a clinical system operating at 2 T. It is employed for transmission of the excitation pulses as well as the received NMR signal. In this way, RF flux guide/coil combinations can be used in experiments with any nuclei without the need for an additional coil for excitation. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 23B: 44–49, 2004.
A mobile NMR device for measurements of porosity and pore size distributions of drilled core samples
Authors: Anferova S. , Anferov V. , Rata D.G. , Blümich B. , Arnold J. , Clauser C. , Blümler P. , Raich H.
Published: October 2004

A new mobile NMR scanner has been designed with a Halbach magnet for measurements of porosity and pore‐size distributions of water‐saturated cylindrical geological cores with diameters up to 60 mm. It is light (∼8 kg) and has a sufficiently homogeneous magnetic field in a large and accessible cylindrical volume. Practical aspects of the sensor construction are described. First experimental results obtained with the mobile Halbach sensor are reported in an attempt to measure porosity and pore‐size distributions in geological drilled cores. Compared to the NMR‐MOUSE®, the Halbach tool is more sensitive, and porosities can be determined down to 3%. The scanner is a laboratory prototype of a future tool for measuring porosity and pore‐size distributions of standard‐size cores drilled from the ocean floor. The tool is particularly attractive for use on research vessels and on logging platforms. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 23B: 26–32, 2004.
Structure and connections of the thalamic reticular nucleus: Advancing views over half a century
Authors: Guillery R.W. , Harting John K.
Published: October 2004

The advance of knowledge of the thalamic reticular nucleus and its connections has been reviewed and Max Cowan's contributions to this knowledge and to the methods used for studying the nucleus have been summarized. Whereas 50 years ago the nucleus was seen as a diffusely organized cell group closely related to the brain stem reticular formation, it can now be seen as a complex, tightly organized entity that has a significant inhibitory, modulatory action on the thalamic relay to cortex. The nucleus is under the control, on the one hand, of topographically organized afferents from the cerebral cortex and the thalamus, and on the other of more diffuse afferents from brain stem, basal forebrain, and other regions. Whereas the second group of afferents can be expected to have global actions on thalamocortical transmission, relevant for overall attentive state, the former group will have local actions, modulating transmission through the thalamus to cortex with highly specific local effects. Since it appears that all areas of cortex and all parts of the thalamus are linked directly to the reticular nucleus, it now becomes important to define how the several pathways that pass through the thalamus relate to each other in their reticular connections. J. Comp. Neurol. 463:360–371, 2003. © 2003 Wiley‐Liss, Inc.
Quantitative stereological evaluation of the gracile and cuneate nuclei and their projection neurons in the rat
Authors: Bermejo Pedro E. , Jiménez Cristina E. , Torres Cristina V. , Avendaño Carlos
Published: October 2004

Stereological methods were employed to estimate the volume and neuron numbers of the rat dorsal column nuclei (DCN). These methods were applied to Nissl‐stained sections from control animals and cases that received injections of horseradish peroxidase in the thalamus, the cerebellum, or the spinal cord. Additional cases received combinations of fluorescent tracers in the same structures, to examine whether some of the retrogradely labeled neurons sent collaterals to different targets. The mean volume of the DCN is 0.81 mm3 (range 0.65–1.10 mm3), of which 3%, 39%, and 59% correspond, respectively, to the nucleus of Bischoff (Bi), the gracile (Gr), and the cuneate (Cu) nuclei. Within Cu, the middle division (CuM) is the largest (42%), followed by the rostral (CuR; 36%) and caudal (CuC; 22%) divisions. The mean total number of neurons in the DCN is 16,000 (range 12,400–19,500), of which 2.4%, 34.0% and 63.6% correspond, respectively, to Bi, Gr, and Cu. Within Cu, CuM contains 48% of all neurons, and 27% correspond to CuR and 25% to CuC. Interanimal variability is moderate for the whole DCN and Cu but increases when individual nuclei are considered. About 80% of DCN neurons project to the thalamus, 3% to the spinal cord, and 7% to the cerebellum. Thalamic‐projecting cells are more numerous in CuM and Gr (83%), and relatively less common in Bi and CuC (72–74%). Most of the DCN neurons projecting to the spinal cord appear in CuC and CuM. Two‐thirds of the neurons projecting to the cerebellum are located in CuR, 20% in CuM, and 15% in Gr. A small fraction of neurons projects simultaneously to spinal cord and thalamus. J. Comp. Neurol. 463:419–433, 2003. © 2003 Wiley‐Liss, Inc.
Mitochondria are redistributed in Drosophila photoreceptors lacking Milton, a kinesin‐associated protein
Authors: Górska‐Andrzejak J. , Stowers R.S. , Borycz J. , Kostyleva R. , Schwarz T.L. , Meinertzhagen I.A.
Published: October 2004

Photoreceptors are richly supplied with mitochondria, where they are required to meet the energetic demands, in the soma, of phototransduction and, in the terminal, of neurotransmitter release. Compromising the latter, we have made photoreceptors R1–R6 in Drosophila ommatidia homozygous for either of two alleles, milt186 and milt92, of milton in whole‐eye mosaics. Such mutant photoreceptors fail to target mitochondria to their terminals. We show from quantitative electron microscopy (EM) that mitochondria are totally lacking at the terminal but nevertheless abundant and present throughout the soma, where their distribution differs from that of control ommatidia, however, being more heavily concentrated in the nuclear region. Mitochondria are sparse at the basalmost level of mutant ommatidia, and are lacking beneath the basement membrane, in the axons and terminals of these cells. The absence of mitochondria from R1–R6 terminals and concommitant reductions in synaptic vesicle packing density, previously reported, we show here are accompanied by reduced immunoreactivity to the photoreceptor transmitter histamine but not by any change in total head histamine content, as determined by high‐performance liquid chromatography. Mutant terminals also contain vesicle profiles with a wider range of sizes. These two phenotypes suggest that the reduced availability of ATP when mutant terminals lack a mitochondrial supply compromises their ability to pump histamine into synaptic vesicles and perturbs membrane distribution within the terminal. In addition, a band of somata in the lamina cortex, at least some of which are postsynaptic neurons not homozygous for milton, also shows altered mitochondrial targeting, with abnormal clusters of mitochondria, as visualized by immunolabeling with anti‐hsp and by serial EM. Within the lamina, terminals of mutant photoreceptors are penetrated by neighboring cells with invaginations that frequently contain mitochondria, suggesting that a mechanism exists for intercellular metabolic support. Our findings indicate the direct and compensatory responses in a population of neurons when mitochondria are not correctly targeted to their synaptic terminals. J. Comp. Neurol. 463:372–388, 2003. © 2003 Wiley‐Liss, Inc.
Subcellular relationships between cholinergic terminals and estrogen receptor‐α in the dorsal hippocampus
Authors: Towart Laura A. , Alves Stephen E. , Znamensky Vladimir , Hayashi Shinji , McEwen Bruce S. , Milner Teresa A.
Published: October 2004

Cholinergic septohippocampal neurons are affected by circulating estrogens. Previously, we found that extranuclear estrogen receptor‐α (ERα) immunoreactivity in presynaptic profiles had an overlapping distribution with cholinergic afferents in the rat hippocampal formation. To determine the subcellular relationships between cholinergic presynaptic profiles and ERα, hippocampal sections were dually immunolabeled for vesicular acetylcholine transporter (VAChT) and ERα and examined by electron microscopy. Within the hippocampal formation, immunoreactivities for VAChT and ERα both were presynaptic, although their subcellular targeting was distinct. VAChT immunoreactivity was found exclusively within presynaptic profiles and was associated with small synaptic vesicles, which usually filled axon terminals. VAChT‐labeled presynaptic profiles were most concentrated in stratum oriens of the hippocampal CA1 region and dentate inner molecular layer and hilus. In contrast, ERα immunoreactivity was found in clusters affiliated either with select vesicles or with the plasmalemma within preterminal axons and axon terminals. ERα‐immunoreactive (IR) presynaptic profiles were more evenly distributed between hippocampal lamina than VAChT‐IR profiles. Quantitative ultrastructural analysis revealed that VAChT‐IR presynaptic profiles contained ERα immunoreactivity (ranging from 3% to 17%, depending on the lamina). Additionally, VAChT‐IR presynaptic profiles apposed ERα‐IR dendritic spines, presynaptic profiles, and glial profiles; many of the latter two types of profiles abutted unlabeled dendritic spines that received asymmetric (excitatory‐type) synapses from unlabeled terminals. The presence of ERα immunoreactivity in cholinergic terminals suggests that estrogen could rapidly and directly affect the local release and/or uptake of acetylcholine. The affiliation of cholinergic terminals with excitatory terminals near ERα‐labeled dendritic spines or glial profiles suggests that alterations in acetylcholine release could indirectly affect estrogen‐modulated structural plasticity. J. Comp. Neurol. 463:390–401, 2003. © 2003 Wiley‐Liss, Inc.
Projections from the rhomboid nucleus of the bed nuclei of the stria terminalis: Implications for cerebral hemisphere regulation of ingestive behaviors
Authors: Dong Hong‐Wei , Swanson Larry W.
Published: October 2004

The basic organization of an exceptionally complex pattern of axonal projections from one distinct cell group of the bed nuclei of the stria terminalis, the rhomboid nucleus (BSTrh), was analyzed with the PHAL anterograde tract‐tracing method in rats. Brain areas that receive a strong to moderate input from the BSTrh fall into nine general categories:central autonomic control network(central amygdalar nucleus, descending hypothalamic paraventricular nucleus, parasubthalamic nucleus and dorsal lateral hypothalamic area, ventrolateral periaqueductal gray, lateral parabrachial nucleus and caudal nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and salivatory nuclei),gustatory system(rostral nucleus of the solitary tract and medial parabrachial nucleus),neuroendocrine system(periventricular and paraventricular hypothalamic nuclei, hypothalamic visceromotor pattern generator network),orofaciopharyngeal motor control(rostral tip of the dorsal nucleus ambiguus, parvicellular reticular nucleus, retrorubral area, and lateral mesencephalic reticular nucleus),respiratory control(lateral nucleus of the solitary tract),locomotor or exploratory behavior control and reward prediction(nucleus accumbens, substantia innominata, and ventral tegmental area),ingestive behavior control(descending paraventricular nucleus and dorsal lateral hypothalamic area),thalamocortical feedback loops(medial‐midline‐intralaminar thalamus), andbehavioral state control(dorsal raphé and locus coeruleus). Its pattern of axonal projections and its position in the basal telencephalon suggest that the BSTrh is part of a striatopallidal differentiation involved in modulating the expression of ingestive behaviors, although it may have other functions as well. J. Comp. Neurol. 463:434–472, 2003. © 2003 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor‐, neurotrophin‐3‐, and tyrosine kinase receptor‐like immunoreactivity in lingual taste bud fields of mature hamster after sensory denervation
Authors: Ganchrow Donald , Ganchrow Judith R. , Verdin‐Alcazar Mary , Whitehead Mark C.
Published: October 2004

Unlike lingual taste buds in most mammals, fungiform buds on the anterior tongue of mature hamster survive sensory denervation. The role of the neurotrophin ligands, brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3), and their respective tyrosine kinase (Trk) receptors, TrkB and TrkC, in denervated taste buds is not known. The present report investigates changes in the degree of gemmal cell immunoreactivity (IR) (i.e., number of immunoreactive cells/bud profile) and density of nerve fiber‐IR of these markers in unilaterally denervated mature hamsters. The fungiform bud field after chorda tympani/lingual nerve resection is compared with the nerve‐dependent, posterior tongue foliate and circumvallate bud fields after glossopharyngeal nerve resection. Four weeks post lesion, the number of denervated fungiform buds matched that on the unoperated side, whereas denervated foliate and circumvallate bud counts decreased by 72% and 38%, respectively. In taste buds that survived on the posterior tongue, the degree of foliate bud cell BDNF‐, NT‐3‐, and TrkB‐like IR, and circumvallate bud cell BDNF‐ and NT‐3‐like IR, significantly decreased compared with the unoperated side. In contrast, for anterior tongue fungiform bud cells, the degree of neurotrophin‐ and receptor‐like IR was relatively less affected: NT‐3‐ and TrkB‐like IR were unchanged; BDNF‐like IR, although significantly decreased, was also maintained. Moreover, TrkB‐like fiber IR was essentially eliminated within and surrounding fungiform buds. Hence, NT‐3‐, BDNF‐, and TrkB‐like IR in fungiform gemmal cells may reflect an autocrine capacity promoting survival. Because TrkC‐like IR in bud cells is absent (i.e., immunonegative), and sparse in fibers intragemmally and perigemmally, NT‐3 may also bind to bud cell TrkB so as to sustain fungiform gemmal cell viability post denervation. J. Comp. Neurol. 455:25–39, 2003. © 2002 Wiley‐Liss, Inc.
On the evolution of sharp fronts for the quasi‐geostrophic equation
Authors: Rodrigo José Luis
Published: October 2004

We consider the problem of the evolution of sharp fronts for the surface quasi‐geostrophic (QG) equation. This problem is the analogue to the vortex patch problem for the two‐dimensional Euler equation.

The special interest of the quasi‐geostrophic equation lies in its strong similarities with the three‐dimensional Euler equation, while being a two‐dimen‐sional model. In particular, an analogue of the problem considered here, the evolution of sharp fronts for QG, is the evolution of a vortex line for the three‐dimensional Euler equation. The rigorous derivation of an equation for the evolution of a vortex line is still an open problem. The influence of the singularity appearing in the velocity when using the Biot‐Savart law still needs to be understood.

We present two derivations for the evolution of a periodic sharp front. The first one, heuristic, shows the presence of a logarithmic singularity in the velocity, while the second, making use of weak solutions, obtains a rigorous equation for the evolution explaining the influence of that term in the evolution of the curve.

Finally, using a Nash‐Moser argument as the main tool, we obtain local existence and uniqueness of a solution for the derived equation in the C∞ case. © 2004 Wiley Periodicals, Inc.
Transport inequalities, gradient estimates, entropy and Ricci curvature
Authors: von Renesse Max‐K. , Sturm Karl‐Theodor
Published: October 2004

We present various characterizations of uniform lower bounds for the Ricci curvature of a smooth Riemannian manifold M in terms of convexity properties of the entropy (considered as a function on the space of probability measures on M) as well as in terms of transportation inequalities for volume measures, heat kernels, and Brownian motions and in terms of gradient estimates for the heat semigroup. © 2004 Wiley Periodicals, Inc.
Photochemistry of Molecules Relevant to the Atmosphere: Photodissociation of Nitric Acid in the Gas Phase
Authors: Huber J. Robert
Published: October 2004

This Minireview gives an account of the photochemical decay of nitric acid HNO3 in the gas phase, which has been well investigated under bulk and molecular‐beam conditions. Due to the importance of this molecule in atmospheric chemistry, attention was paid to the irradiation regions around 300 and 200 nm, where solar photolysis of HNO3 is expected to be particularly efficient. While the low‐energy region is characterized by the products OH and NO2, the high‐energy region gives rise to a variety of photochemical decay pathways, dominated by channels which lead to the products HONO+O in different electronic states.
Myogenic regulatory factors: Redundant or specific functions? Lessons from Xenopus
Authors: Chanoine Christophe , Della Gaspera Bruno , Charbonnier Frédéric
Published: October 2004

The discovery, in the late 1980s, of the MyoD gene family of muscle transcription factors has proved to be a milestone in understanding the molecular events controlling the specification and differentiation of the muscle lineage. From gene knock‐out mice experiments progressively emerged the idea that each myogenic regulatory factor (MRF) has evolved a specialized as well as a redundant role in muscle differentiation. To date, MyoD serves as a paradigm for the MRF mode of function. The features of gene regulation by MyoD support a model in which subprograms of gene expression are achieved by the combination of promoter‐specific regulation of MyoD binding and MyoD‐mediated binding of various ancillary proteins. This binding likely includes site‐specific chromatin reorganization by means of direct or indirect interaction with remodeling enzymes. In this cascade of molecular events leading to the proper and reproducible activation of muscle gene expression, the role and mode of function of other MRFs still remains largely unclear. Recent in vivo findings using the Xenopus embryo model strongly support the concept that a single MRF can specifically control a subset of muscle genes and, thus, can be substituted by other MRFs albeit with dramatically lower efficiency. The topic of this review is to summarize the molecular data accounting for a redundant and/or specific involvement of each member of the MyoD family in myogenesis in the light of recent studies on the Xenopus model. Developmental Dynamics 231:662–270, 2004. © 2004 Wiley‐Liss, Inc.
Mouse myotomes pairs exhibit left–right asymmetric expression of MLC3F and α‐skeletal actin
Authors: Golding Jon P. , Partridge Terence A. , Beauchamp Jonathan R. , King Tim , Brown Nigel A. , Gassmann Martin , Zammit Peter S.
Published: October 2004

Most muscle originates from the myotomal compartment of the somites, paired structures flanking the neural tube. Whereas vertebrate embryos show molecular and morphological asymmetry about the left–right body axis, somitic myogenesis is thought to occur symmetrically. Here, we provide the first evidence that myotome pairs are transiently left–right asymmetric, with higher expression of α‐skeletal actin and myosin light chain 3F (MLC3F) on the left side between embryonic day 9.5–10.25. In iv mutants with situs inversus, the asymmetric expression of α‐skeletal actin and MLC3F was inverted, showing that this process is regulated by global left–right axis cues, initiated before gastrulation. However, although left–sided identity is later maintained by Pitx2 genes, we found that Pitx2c null embryos have normal left‐biased expression of α‐skeletal actin and MLC3F. Myotome asymmetry, therefore, is downstream of the iv mutation but upstream of, or unrelated to, the Pitx2c pathway. Developmental Dynamics 231:795–800, 2004. © 2004 Wiley‐Liss, Inc.
Early fin primordia of zebrafish larvae regenerate by a similar growth control mechanism with adult regeneration
Authors: Kawakami Atsushi , Fukazawa Taro , Takeda Hiroyuki
Published: October 2004

Some vertebrate species, including urodele amphibians and teleost fish, have the remarkable ability of regenerating lost body parts. Regeneration studies have been focused on adult tissues, because it is unclear whether or not the repairs of injured tissues during early developmental stages have the same molecular base as that of adult regeneration. Here, we present evidence that a similar cellular and molecular mechanism to adult regeneration operates in the repair process of early zebrafish fin primordia, which are composed of epithelial and mesenchymal cells. We show that larval fin repair occurs through the formation of wound epithelium and blastema‐like proliferating cells. Cell proliferation is first induced in the distal‐most region and propagates to more proximal regions, as in adult regeneration. We also show that fibroblast growth factor signaling helps induce cell division. Our results suggest that the regeneration machinery directing cell proliferation in response to injury may exist from the early developmental stages. Developmental Dynamics 231:693–699, 2004. © 2004 Wiley‐Liss, Inc.
Interleukin‐11 signaling is required for the differentiation of natural killer cells at the maternal–fetal interface
Authors: Ain Rupasri , Trinh My‐Linh , Soares Michael J.
Published: October 2004

Interleukin‐11 (IL‐11) is a multifunctional hematopoietic growth factor that has been implicated in the control of reproduction. Studies on IL‐11 receptor‐α (IL‐11Rα) ‐deficient mice showed that female mice are infertile due to defective decidualization. In this report, we evaluated the development of decidual cells, immune cells, and the vasculature associated with the implantation site of IL‐11Rα–deficient mice; with the aim of better understanding the nature of the fertility defect. Messenger RNAs for decidual differentiation, such as decidual prolactin‐related protein and prolactin‐like protein‐J are expressed in the IL‐11Rα mutant. However, the number of decidual cells expressing these genes is decreased in the mutant compared with the wild‐type control. Although, trophoblast cells differentiate and express placental lactogen‐I in the IL‐11Rα–deficient uterine environment, they fail to progress and expand in number. Defects in the organization of the decidual vasculature were also apparent in the IL‐11Rα mutant uterus. The most dramatic effect of IL‐11 signaling was on the hematopoietic environment of the uterine decidua. Differentiated/perforin‐expressing uterine natural killer (NK) cells were virtually absent from implantation sites of IL‐11Rα mutant mice. NK cell precursors were capable of homing to the IL‐11Rα–deficient uterus and a known regulator of NK cell differentiation; IL‐15 was expressed in the IL‐11Rα mutant uterus. Splenic NK cells from IL‐11Rα mutant mice were also able to respond to IL‐15 in vitro. Thus, the defect in NK precursor cell maturation was not intrinsic to the NK precursor cells but was dependent upon the tissue environment. In summary, IL‐11 signaling is required for decidual‐specific maturation of NK cells. Developmental Dynamics 231:700–708, 2004. © 2004 Wiley‐Liss, Inc.
Ventral otic cell lines as developmental models of auditory epithelial and neural precursors
Authors: Lawoko‐Kerali G. , Milo M. , Davies D. , Halsall A. , Helyer R. , Johnson C.M. , Rivolta M.N. , Tones M.A. , Holley M.C.
Published: October 2004

Conditionally immortal cell lines were established from the ventral otocyst of the Immortomouse at embryonic day 10.5 and selected to represent precursors of auditory sensory neural and epithelial cells. Selection was based upon dissection, tissue‐specific markers, and expression of the transcription factor GATA3. Two cell lines expressed GATA3 but possessed intrinsically different genetic programs under differentiating conditions. US/VOT‐E36 represented epithelial progenitors with potential to differentiate into sensory and nonsensory epithelial cells. US/VOT‐N33 represented migrating neuroblasts. Under differentiating conditions in vitro the cell lines expressed very different gene expression profiles. Expression of several cell‐ and tissue‐specific markers, including the transcription factors Pax2, GATA3, and NeuroD, differed between the cell lines in a pattern consistent with that observed between their counterparts in vivo. We suggest that these and other conditionally immortal cell lines can be used to study transient events in development against different backgrounds of cell competence. Developmental Dynamics 231:801–814, 2004. © 2004 Wiley‐Liss, Inc.
Expression of Nkx2‐5‐GFP bacterial artificial chromosome transgenic mice closely resembles endogenous Nkx2‐5 gene activity
Authors: Chi Xuan , Zhang Shu‐xing , Yu Wei , DeMayo Francesco J. , Rosenberg Susan M. , Schwartz Robert J.
Published: October 2004

Summary: Mouse Nkx2‐5 gene is essential for early heart development and it is regulated by a complex array of regulatory modules. In order to establish an efficient in vivo system for mapping the Nkx2‐5 genomic locus for regulatory regions, we developed improved homologous recombination technology for use in Escherichia coli and then knocked an IRES‐hrGFP reporter gene into Nkx2‐5 gene in a 120 kb Nkx2‐5 bacterial artificial chromosome (BAC) clone. We employed the recombination genes redα and redβ under the pBAD promoter, which was specifically induced by the addition of L‐arabinose. Recombination was selected for by our universal targeting cassette which conferred kanamycin resistance in bacterial cells and neomycin resistance in mammalian cells. Transgenic mouse lines generated from this modified BAC clone closely resembled the endogenous Nkx2‐5 expression in the heart, pylorus sphincter, and spleen, but expression was not detected in the tongue. Nkx2‐5 BAC‐GFP expression was copy number‐dependent and locus site‐independent. BAC transgenics using the GFP reporter offers an efficient model system to study gene expression and regulation. genesis 35:220–226, 2003. © 2003 Wiley‐Liss, Inc.
Insulin‐like growth factor‐binding protein 6 inhibits survival and differentiation of rat oligodendrocyte precursor cells
Authors: Kühl Nicole M. , Hoekstra Dick , De Vries Hans , De Keyser Jacques
Published: October 2004

Insulin‐like growth factor 1 (IGF‐1) is a growth and survival factor for oligodendrocyte lineage cells and promotes myelination. We demonstrate that IGF‐binding protein 6 (IGFBP‐6) is expressed and localized to the Golgi complex in rat oligodendrocyte precursor (O2A) cells. IGFBP‐6 mRNA showed a developmentally regulated expression pattern, displaying a transient decrease during early development, and enhanced levels upon cell maturation. IGFBP‐6 mRNA expression could be reduced by addition of basic fibroblast growth factor and progesterone while estrogen increased IGFBP‐6 mRNA. IGF‐1, platelet‐derived growth factor, and insulin had no effect. When added exogenously, IGFBP‐6 reduced O2A cell survival in the absence of IGF‐1 and inhibited IGF‐1‐stimulated survival in a partially IGF‐1‐dependent and partially IGF‐1‐independent fashion. In addition, IGFBP‐6 reduced the IGF‐stimulated expression of two myelin proteins, CNPase and MAG. Taken together, the data show that IGFBP‐6 is a new negative effector of oligodendrocyte survival and differentiation. © 2003 Wiley‐Liss, Inc.
Oligodendrocytes express functional A1 adenosine receptors that stimulate cellular migration
Authors: Othman Timothy , Yan Henglin , Rivkees Scott A.
Published: October 2004

A1 adenosine receptors (A1ARs) exert important effects in the central nervous system. However, the expression and function of A1ARs in oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLGs) is unclear. To address this issue, we examined A1AR expression during different stages of oligodendrocyte development. Radioreceptor studies showed that membranes prepared from OPCs and OLGs expressed high‐affinity A1ARs with Kd values of 1.35 ± 0.33 and 1.2 ± 0.27 nM for [3H]CCPA, 1.17 ± 0.24 and 1.4 ± 0.34 nM for [3H]DPCPX, respectively. Bmax values were 64.31 ± 6.14 and 75 ± 6 fmol/mg protein for [3H]CCPA, and 153 ± 12 and 205 ± 17.8 fmol/mg protein for [3H]DPCPX, respectively. Activation of A1ARs using N6‐cyclopentyladenosine (CPA) reduced both forskolin‐ and N‐ethylcarboxyamidoadenosine (NECA)‐stimulated cAMP accumulation, but did not affect basal cAMP levels. Activation of A1ARs by CPA stimulated OPC migration, but did not affect cell viability, proliferation, or differentiation. These results show that OPCs and OLGs express functional A1ARs that can stimulate the migration of OPCs. © 2003 Wiley‐Liss, Inc.
Paranodal transverse bands are required for maintenance but not initiation of Nav1.6 sodium channel clustering in CNS optic nerve axons
Authors: Rasband Matthew N. , Taylor Christopher M. , Bansal Rashmi
Published: October 2004

The rapid, efficient, and faithful propagation of action potentials in myelinated nerve fibers depends on the appropriate complement and localization of ion channels. Recent work has suggested that specific voltage‐dependent sodium (Nav) channel isoforms are differentially regulated both spatially and temporally in a myelin‐dependent manner. Since the principal site of axoglial contact occurs at the paranode, we postulated that disrupted paranodal structure might result in altered nodal Nav channel isoform localization and clustering. We have used UDP‐galactose/ceramide galactosyl transferase (CGT)‐deficient mice, which form compact myelin and paranodal loops but lack the transverse bands normally found at the interface of the axon and overlying glial cell, to determine if this structure contributes to the signaling machinery responsible for clustering and localization of distinct Nav channel isoforms. We find that as in control animals, most mutant nodes of Ranvier had Nav1.6 in high‐density clusters in the peripheral and central nervous systems; the localization of Nav1.2 and the protein levels of Nav1.2 and Nav1.6 were also normal in the CGT‐deficient mouse. However, with increasing age, in the mutant mouse we observed a decrease in the total number of nodal Nav1.6 clusters, a decrease in the density of Nav1.6 channels at nodes, and an increase in the average size of the Nav1.6 clusters. Thus, transverse bands are not required for Nav1.6 clustering and localization at nodes or for exclusion of Nav1.2 from myelinated nerve fibers, but are required for the maintenance of nodal Nav1.6 cluster size and density. © 2003 Wiley‐Liss, Inc.