bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bifunctional Ligands that Target Cells Displaying the αvβ3 Integrin
Authors: Owen Robert M. , Carlson Coby B. , Xu Jinwang , Mowery Patricia , Fasella Elisabetta , Kiessling Laura L. 
Published: December 2006

AbstractStrategies to eliminate tumor cells have long been sought. We envisioned that a small molecule could be used to decorate the offending cells with immunogenic carbohydrates and evoke an immune response. To this end, we describe the synthesis of bifunctional ligands possessing two functional motifs: one binds a cell‐surface protein and the other binds a naturally occurring human antibody. Our conjugates combine an RGD‐based peptidomimetic, to target cells displaying the αvβ3 integrin, with the carbohydrate antigen galactosyl‐α(1–3)galactose [Galα(1–3)Gal or α‐Gal]. To generate such bifunctional ligands, we designed and synthesized RGD mimetics 1 b and 2 c, which possess a free amino group for modification. These compounds were used to generate bifunctional derivatives 1 c and 2 d, with dimethyl squarate serving as the linchpin; thus, our synthetic approach is modular. To evaluate the binding of our peptidomimetics to the target αvβ3‐displaying cells, we implemented a cell‐adhesion assay. Results from this assay indicate that the designed, small‐molecule ligands inhibit αvβ3‐dependent cell adhesion. Additionally, our most effective bifunctional ligand exhibits a high degree of selectivity (4000‐fold) for αvβ3 over the related αvβ5 integrin, a result that augurs its utility in specific cell targeting. Finally, we demonstrate that the bifunctional ligands can bind to αvβ3‐positive cells and recruit human anti‐Gal antibodies. These results indicate that both the integrin‐binding and the anti‐Gal‐binding moieties can act simultaneously. Bifunctional conjugates of this type can facilitate the development of new methods for targeting cancer cells by exploiting endogenous antibodies. We anticipate that our modifiable αvβ3‐binding ligands will be valuable in a variety of applications, including drug delivery and tumor targeting.
Caged Capsaicins: New Tools for the Examination of TRPV1 Channels in Somatosensory Neurons
Authors: Gilbert Daniel , Funk Katharina , Dekowski Brigitte , Lechler Ralf , Keller Sandro , Möhrlen Frank , Frings Stephan , Hagen Volker 
Published: December 2006

AbstractThe vanilloid capsaicin,N‐(4‐hydroxy‐3‐methoxybenzyl)‐8‐methylnon‐6‐enamide, is the pungent ingredient of chili peppers and is used in pain research as an activating ligand of heat‐sensitive transduction channels in nociceptive neurons. Here we describe the synthesis and application of two capsaicin derivatives modified at the hydroxy function of the vanillyl motif: α‐carboxy‐4,5‐dimethoxy‐2‐nitrobenzyl‐caged (CDMNB‐caged) capsaicin and {7‐[bis(carboxymethyl)amino]coumarin‐4‐yl}methoxycarbonyl‐caged (BCMACMOC‐caged) capsaicin. These compounds show dramatically reduced pungency, but release active capsaicin upon irradiation with UV light. CDMNB‐caged capsaicin can be used to perform concentration‐jump experiments, while BCMACMOC‐caged capsaicin is membrane‐impermeant and can be applied selectively to the intracellular or extracellular sides of a plasma membrane. Both compounds can serve as valuable research tools in pain physiology.
8‐Hydroxy‐2′‐deoxyguanosine (8‐OH‐dG) as a potential survival biomarker in patients with nonsmall‐cell lung cancer
Authors: Shen Jie , Deininger Prescott , Hunt Jay D. , Zhao Hua 
Published: December 2006

AbstractBACKGROUND.8‐Hydroxy‐2′‐deoxyguanosine (8‐OH‐dG) is 1 of the most abundant oxidative products of cellular DNA. Accumulation of impaired 8‐OH‐dG could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. Therefore, the effects of 8‐OH‐dG on survival in 99 resected nonsmall‐cell lung cancer (NSCLC) patients was evaluated.METHODS.The enzyme‐linked immunosorbent assay was applied to measure the levels of 8‐OH‐dG in tumor DNA. The median levels of 8‐OH‐dG were 6.5 pmol/μg for all study subjects.RESULTS.Patients with low levels of 8‐OH‐dG had significantly longer survival times compared with those with high levels of 8‐OH‐dG (log‐rank test: P < .001). In Cox regression analysis, patients with high levels of 8‐OH‐dG had an over 3‐fold increased hazard of death. In addition, a statistically significant correlation between levels of 8‐OH‐dG and age was noted (rho = 0.206, P = .048). Furthermore, we observed a genotype‐phenotype modification between hOGG1 gene polymorphism (Ser326Cys) and levels of 8‐OH‐dG.CONCLUSIONS.The results demonstrated that levels of 8‐OH‐dG could predict survival in resected NSCLC patients. It is postulated that an intact base excision repair mechanism may reduce the accumulation of oxidative DNA damage that is thought to contribute to the tumor's malignant potential and therefore the risk of death. Cancer 2007 © 2006 American Cancer Society.
Neuropeptide Y activates urocortin 1 neurons in the nonpreganglionic Edinger‐Westphal nucleus
Authors: Gaszner Balázs , Korosi Anikó , Palkovits Miklós , Roubos Eric W. , Kozicz Tamás 
Published: December 2006

AbstractCentral regulatory pathways promoting stress adaptation utilize various neurotransmitters/neuropeptides, such as urocortin 1 (Ucn1) and neuropeptide Y (NPY). Ucn1 is abundantly expressed in the nonpreganglionic Edinger‐Westphal nucleus (npEW), where it is codistributed with NPY‐immunoreactive (ir) terminals. A special role for both neuropeptides has been postulated in stress adaptation. Using double‐labeling immunohistochemistry, we observed close appositions between NPY‐ir terminals and neurons immunoreactive for Ucn1 in the rat, as well as in the human npEW. Therefore, we hypothesized that NPY might control the activity of Ucn1‐positive neurons in the npEW. To test this hypothesis, NPY was injected into the lateral cerebral ventricle of rats, resulting in a strong activation of npEW Ucn1 neurons as revealed by Fos immunohistochemistry. Ucn1 mRNA was also upregulated in the npEW 2 hours after the injection of NPY. In a search for the type of NPY receptor that mediates this NPY‐induced recruitment of npEW‐Ucn1 cells, we found that the great majority of Ucn1 cells exhibited NPY Y5 receptor immunoreactivity, and only a few of the Ucn1 cells coexpressed the Y1 receptor. We concluded that NPY, via NPY Y5 and to a lesser extent via the Y1 receptors, exerts a stimulatory action on Ucn1 cells in the npEW. Further studies are currently in progress to elucidate the significance of this NPY–Ucn1 interaction in the npEW. J. Comp. Neurol. 500:708–719, 2007. © 2006 Wiley‐Liss, Inc.
Anatomical organization of antennal lobe projection neurons in the moth Heliothis virescens
Authors: RØ Helge , Müller Dirk , Mustaparta Hanna 
Published: December 2006

AbstractA prerequisite for understanding how odor information is coded in the central nervous system is to know the morphology and spatial relationship of the principal neurons forming the olfactory pathways. The present account provides an anatomical description of the morphology of the neuronal connections between the antennal lobe and the protocerebrum in the moth Heliothis virescens, a species used for studies of olfactory processing and learning. Intracellular labeling and antennal lobe focal injections with dextran fluorescent markers were combined with neuropil immunostaining and three‐dimensional reconstructions. The experiments revealed four antennocerebral tracts, the inner, middle, outer, and dorsomedial, and eight morphological types of projection neurons in addition to a neuron with an unpaired median soma in the subesophageal ganglion. Multiglomerular projection neurons, present in all but the dorsomedial antennocerebral tract, project in several olfactory foci of the protocerebral neuropil. With few exceptions, these neurons do not innervate the calyces of the mushroom body. Uniglomerular projection neurons appear most numerous in the inner antennocerebral tract but are also present in the outer and dorsomedial tracts. These neurons always ramify in the calyces of the mushroom body and in the lateral horn. The projection areas of the neurons following different tracts are largely separated in the secondary olfactory centers. This is most evident in the lateral horn, whereas, in the calyces, the axonal ramifications are more intermingled. The mushroom body architecture, revealed by neuropil immunolabeling, showed striking similarities to that of other lepidopteran species as well as insects of other taxa. J. Comp. Neurol. 500:658–675, 2007. © 2006 Wiley‐Liss, Inc.
Axonal bias at a representational border in adult rat somatosensory cortex (S1)
Authors: Steen Patricia A. , Mason Matthew , Pham Lanchi , Lefebvre Yann , Hickmott Peter W. 
Published: December 2006

AbstractThe cortex is a highly organized structure and this organization is integral to cortical function. However, the circuitry underlying cortical organization is only partially understood, thus limiting our understanding of cortical function. Within the somatosensory cortex, organization is manifest as a map of the body surface. At the level of the cortical circuitry the horizontal connections of Layer 2/3 express a physiological bias that reflects discontinuities within the somatosensory map. Both excitation and inhibition are smaller when evoked from across a representational border, as compared to when they are evoked from within the representation. This physiological bias may be due to a bias in either the strength or number of synapses and/or the number of axons that cross this border and the extent of their arborization. In this study we used both an anterograde (Phaseolus vulgaris leucoagglutinin) and a retrograde (cholera toxin B) tracer to examine Layer 2/3 horizontal projections in rat S1. We determined that there is a bias in the amount of horizontal axonal projections that cross the forepaw/lower jaw border as compared to projections remaining within an individual representation. This bias in axonal projection and the correlated bias in excitation and inhibition may underlie the expression of the representational border. J. Comp. Neurol. 500:634–645, 2007. © 2006 Wiley‐Liss, Inc.
Premotor circuits controlling eyelid movements in conjunction with vertical saccades in the cat: II. Interstitial nucleus of Cajal
Authors: Chen Bingzhong , May Paul J. 
Published: December 2006

AbstractVertical saccadic eye movements are accompanied by concurrent eyelid movements in the same direction. The interstitial nucleus of Cajal (InC) controls eye position for vertical eye movements and may also control saccade‐related lid position as well. This study investigates whether the InC serves as a premotor center for eyelid saccades, by employing dual‐tracer methods in cats to label both the projections of the InC and the motoneurons supplying the levator palpebrae superioris (LPS) muscle, which lie in the caudal central subdivision (CCS) of the oculomotor complex. Injections of biotinylated dextran amine (BDA) into the InC anterogradely labeled axons that terminated bilaterally throughout the CCS and in the oculomotor nuclei proper. Labeled terminals lay in close association with labeled LPS motoneurons, which were retrogradely labeled following injections of wheat germ agglutinin‐conjugated horseradish peroxidase (WGA‐HRP) into the muscle. Ultrastructural investigation revealed that most terminals contained spherical vesicles and formed asymmetric synaptic contacts with the labeled motoneurons. These results strongly suggest that the InC monosynaptically controls lid movements in conjunction with vertical eye movements, including saccades. To identify the neurons of origin for this pathway, WGA‐HRP injections were centered in the CCS. These experiments indicate that lid and eye motoneurons may share a common source of bilateral InC input. Thus, a common vertical position signal may be employed to maintain the lid and eye at appropriate elevations during fixation, such that the lid sits just above the pupil, allowing unobstructed vision, but at the ready to protect the cornea. J. Comp. Neurol. 500:676–692, 2007. © 2006 Wiley‐Liss, Inc.
Distribution of soluble guanylyl cyclase in rat retina
Authors: Ding Jin‐Dong , Weinberg Richard J. 
Published: December 2006

AbstractThe nitric oxide (NO)‐cGMP pathway is implicated in modulation of visual information processing in the retina. Despite numerous functional studies of this pathway, information about the retinal distribution of the major downstream effector of NO, soluble guanylyl cyclase (sGC), is very limited. In the present work, we have used immunohistochemistry and multiple labeling to determine the distribution of sGC in rat retina. sGC was present at high levels in inner retina but barely detectable in outer retina. Photoreceptors and horizontal cells, as well as Müller cells, were immunonegative, whereas retinal ganglion cells exhibited moderate staining for sGC. Strong immunostaining was found in subpopulations of bipolar and amacrine cells, but staining was weak in rod bipolar cells, and AII amacrine cells were immunonegative. Double labeling of sGC with neuronal nitric oxide synthase showed that the two proteins are generally located in adjacent puncta in inner plexiform layer, implying paracrine interactions. Our results suggest that the NO‐cGMP pathway modulates the neural circuitry in inner retina, preferentially within the cone pathway. J. Comp. Neurol. 500:734–745, 2007. © 2006 Wiley‐Liss, Inc.
Vessicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus
Authors: Zhou Jianxun , Nannapaneni Naveen , Shore Susan 
Published: December 2006

AbstractProjections of glutamatergic somatosensory and auditory fibers to the cochlear nucleus (CN) are mostly nonoverlapping: projections from the spinal trigeminal nucleus (Sp5) terminate primarily in the granule cell domains (GCD) of CN, whereas type I auditory nerve fibers (ANFs) project to the magnocellular areas of the VCN (VCNm) and deep layers of Dorsal CN (DCN). Vesicular glutamate transporters (VGLUTs), which selectively package glutamate into synaptic vesicles, have different isoforms associated with distinct subtypes of excitatory glutamatergic neurons. Here we examined the distributions of VGLUT1 and VGLU2 expression in the CN and their colocalization with Sp5 and ANF terminals following injections of anterograde tracers into Sp5 and the cochlea in the guinea pig. The CN regions that showed the most intense expression of VGLUT1 and VGLUT2 were largely nonoverlapping and were consistent with ANF and Sp5 projections, respectively: VGLUT1 was highly expressed in VCNm and the molecular layer of the DCN, whereas VGLUT2 was expressed predominantly in the GCD. Half (47% ± 3%) of the Sp5 mossy fiber endings colabeled with VGLUT2, but few (2.5% ± 1%) colabeled with VGLUT1. In contrast, ANFs colabeled predominantly with VGLUT1. The pathway‐specific expression of VGLUT isoforms in the CN may be associated with the intrinsic synaptic properties that are unique to each sensory pathway. J. Comp. Neurol. 500:777–787, 2007. © 2006 Wiley‐Liss, Inc.
Taste‐evoked Fos expression in nitrergic neurons in the nucleus of the solitary tract and reticular formation of the rat
Authors: Travers Susan P. , Travers Joseph B. 
Published: December 2006

AbstractThe current investigation used double labeling for NADPHd and Fos‐like immunoreactivity to define the relationship between nitric oxide synthase‐containing neural elements and taste‐activated neurons in the nucleus of the solitary tract (NST) and subjacent reticular formation (RF). Stimulation of awake rats with citric acid and quinine resulted in significant increases in the numbers of double‐labeled neurons in both the NST and RF, suggesting that some medullary gustatory neurons utilize nitric oxide (NO) as a transmitter. Overall, double‐labeled neurons were most numerous in the caudal reaches of the gustatory zone of the NST, where taste neurons receive inputs from the IXth nerve, suggesting a preferential role for NO neurons in processing gustatory inputs from the posterior oral cavity. However, double‐labeled neurons also exhibited a preferential distribution depending on the gustatory stimulus. In the NST, double‐labeled neurons were most numerous in the rostral central subnucleus after either stimulus but had a medial bias after quinine stimulation. In the RF, after citric acid stimulation, there was a cluster of double‐labeled neurons with distinctive large soma in the parvicellular division of the lateral RF, subjacent to the rostral tip of NST. In contrast, in response to quinine, there was a cluster of double‐labeled neurons with much smaller soma in the intermediate zone of the medial RF, a few hundred micrometers caudal to the citric acid cluster. These differential distributions of double‐labeled neurons in the NST and RF suggest a role for NO in stimulus‐specific gustatory autonomic and oromotor reflex circuits. J. Comp. Neurol. 500:746–760, 2007. © 2006 Wiley‐Liss, Inc.
Comparative analysis of the subcellular and subsynaptic localization of mGluR1a and mGluR5 metabotropic glutamate receptors in the shell and core of the nucleus accumbens in rat and monkey
Authors: Mitrano Darlene A. , Smith Yoland 
Published: December 2006

AbstractGroup I metabotropic glutamate receptors (mGluRs) play critical roles in synaptic plasticity and drug addiction. To characterize potential sites whereby these receptors mediate their effects in the ventral striatum, we studied the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the shell and core of the nucleus accumbens in rat and monkey. In both species, group I mGluRs are mainly postsynaptic in dendrites and spines, with rare presynaptic labeling in unmyelinated axons. Minor, yet significant, differences in proportions of specific immunoreactive elements were found between the accumbens shell and the accumbens core in monkey. At the subsynaptic level, significant differences were found in the proportion of plasma membrane‐bound mGluR5 labeling between species. In dendrites, spines, and unmyelinated axons, a significantly larger proportion of mGluR5 labeling was bound to the plasma membrane in rats (50–70%) than in monkeys (30–50%). Conversely, mGluR1a displayed the same pattern of immunogold labeling in the two species. Electron microscopic colocalization studies revealed 30% colocalization of mGluR1a and mGluR5 in dendrites and as much as 50–65% in spines in both compartments of the rat accumbens. Both group I mGluRs were significantly expressed in D1‐immunoreactive dendritic processes (60–75% colocalization) and spines (30–50%) of striatal projection neurons as well as dendrites of cholinergic (30–70%) and parvalbumin‐containing (70–85%) interneurons. These findings highlight the widespread expression of group I mGluRs in projection neurons and interneurons of the shell and core of the nucleus accumbens, providing a solid foundation for regulatory and therapeutic functions of group I mGluRs in reward‐related behaviors and drug addiction. J. Comp. Neurol. 500:788–806, 2007. © 2006 Wiley‐Liss, Inc.
FTY720 enhances the activation‐induced apoptosis of donor T cells and modulates graft‐versus‐host disease
Authors: Hashimoto Daigo , Asakura Shoji , Matsuoka Ken‐ichi , Sakoda Yukimi , Koyama Motoko , Aoyama Kazutoshi , Tanimoto Mitsune , Teshima Takanori 
Published: December 2006

AbstractFTY720 is a novel immunosuppressant that improves the outcomes after solid organ and bone marrow transplantation (BMT) due to the sequestration of T cells into LN. We tested the hypothesis that the sequestration of donor T cells in LN by FTY720 would enhance their interaction with host APC, thus causing a greater degree of activation‐induced apoptosis of alloreactive T cells, and thereby resulting in a reduction of graft‐vs.‐host disease (GVHD). The short‐term administration of FTY720 improved the recipient survival after allogeneic BMT. FTY720 treatment facilitated a rapid contraction of the donor T cell pool in association with an increased degree of apoptosis of donor T cells. The donor T cell reactivity to host alloantigens was diminished in host's LN and adoptive transfer of donor T cells isolated from LN of FTY720‐treated recipients of allogeneic BMT induced less severe GVHD in secondary recipients than the transfer from controls. Caspase‐dependent apoptosis was involved in this mechanism because FTY720‐induced protection was abrogated when a pan‐caspase inhibitor was administered. These findings thus demonstrate the presence of a novel mechanism by which FTY720 modulates the allogeneic T cell responses: namely, by the induction of activation‐induced apoptosis of alloreactive T cells in LN.
Mast cell‐expressed complement receptor, not TLR2, is the main detector of zymosan in peritonitis
Authors: Mullaly Sarah C. , Kubes Paul 
Published: December 2006

AbstractThe in vitro macrophage response to zymosan has been attributed to Toll‐like receptor 2 (TLR2). Whether TLR2 is obligatory for the zymosan‐induced in vivo response has not been assessed. The importance of this question is underscored by the fact that zymosan activates complement in a cell‐independent manner. We have investigated whether the in vitro observation of TLR2 as the dominant zymosan receptor on macrophages would translate to an experimental peritonitis model in vivo. We have treated mice with zymosan, resulting in significant leukocyte (primarily neutrophil) accumulation in the peritoneum at 4 h. Zymosan‐mediated leukocyte recruitment was TLR2 independent, but was predominantly dependent on the complement components, C3 and C5a with a minor contribution from LTB4. Peritoneal neutrophilia was 50% mast cell dependent and this defect was reproduced using C5a receptor (C5aR)‐deficient mast cells in mast cell‐deficient mice, suggesting that C5aR is responsible for mast cell activation following zymosan challenge. By 24 h, the response to zymosan involved primarily monocyte recruitment and was C3 and C5aR independent. Taken together, these studies indicate that the in vivo inflammatory response to zymosan does not necessarily mimic the TLR2 dependence observed in vitro, and that complement plays a dominant role in early, but not late, zymosan‐mediated peritonitis.