bluuebunny/crossref_metadata_2025_split huggingface dataset:
What the papers say: Where is the somatic mutation that causes aging?
Authors: Driver Christopher 
Published: October 2004

AbstractIt 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

AbstractMeiotic 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

AbstractThe 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

AbstractImmunotherapeutic 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

AbstractA 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

AbstractIn 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

AbstractThe [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

AbstractArticular 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

AbstractMagnets 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

AbstractRadio 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

AbstractA 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

AbstractThe 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

AbstractStereological 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

AbstractPhotoreceptors 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

AbstractCholinergic 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

AbstractThe 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.