bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphogenesis of the First Blood Vessels
Authors: DRAKE CHRISTOPHER J. , HUNGERFORD JILL E. , LITTLE CHARLES D. 
Published: February 2006

ABSTRACT: The initial phase of vessel formation is the establishment of nascent endothelial tubes from mesodermal precursor cells. Development of the vascular epithelium is examined using the transcription factor TAL1 as a marker of endothelial precursor cells (angioblasts), and a functional assay based on intact, whole‐mounted quail embryos. Experimental studies examining the role(s) of integrins and vascular endothelial growth factor (VEGF) establish that integrin‐mediated cell adhesion is necessary for normal endothelial tube formation and that stimulation of embryonic endothelial cells with exogenous VEGF results in a massive “fusion” of vessels and the obliteration of normally avascular zones.The second phase of vessel morphogenesis is assembly of the vessel wall. To understand the process by which mesenchyme gives rise to vascular smooth muscle, a novel monoclonal antibody, 1E12, that recognizes smooth muscle precursor cells was used. Additionally, development of the vessel wall was examined using the expression of extracellular matrix proteins as markers. Comparison of labeling patterns of 1E12 and the extracelllar matrix molecles fibulin‐1 and fibrillin‐2 indicate vessel wall heterogeneity at the earliest stages of development; thus smooth muscle cell diversity is manifested during the differentiation and assembly of the vessel wall. From these studies it is postulated that the extracellular matrix composition of the vessel wall may prove to be the best marker of smooth muscle diversity.The data are discussed in the context of recent work by others, especially provocative new studies suggesting an endothelial origin for vascular smooth muscle cells. Also discussed is recent work that provides clues to the mechanism of vascular smooth muscle induction and recruitment. Based on these findings, vascular smooth muscle cells can be thought of as existing along a continuum of phenotypes. This spectrum varies from mainly matrix‐producing cells to primarily contractile cells; thus no one cell type typifies vascular smooth muscle. This view of the smooth muscle cell is considered in terms of a contrasting opinion that views smooth muscle cell as existing in either a synthetic or proliferative state.
Gs Protein‐Coupled Serotonin Receptors: Receptor Isoforms and Functional Differences
Authors: HAMBLIN M. W. , GUTHRIE C. R. , KOHEN R. , HEIDMANN D.E. A. 
Published: February 2006

ABSTRACT: Three distinct mammalian Gs coupled serotonin receptor genes have been identified, 5‐HT4, 5‐ht6, and 5‐HT7, which produce at least seven different functional receptors through alternative splicing. One of the chief questions facing workers in this area mirrors that confronting the serotonin receptor field as a whole: why so many subtypes? The answer to this question is made more elusive at present by two further considerations. First, there may well be additional Gs coupled receptor subtypes yet to be described. Secondly, although the various isoforms of 5‐HT4 and 5‐HT7 have been shown to be functional in in vitro assays, it remains to be shown that all isoforms have biological significance.This paper will summarize some of the differences at the molecular and cellular level that are becoming apparent among the 5‐HT4, 5‐ht6 and 5‐HT7 receptor subtypes and their various isoforms. As an example, it will focus on the 5‐HT7 system, and describe recent developments in ascribing particular functions to differences due to alternative splicing.
A Three‐State Receptor Model: Predictions of Multiple Agonist Pharmacology for the Same Receptor Typea
Authors: CARAMELLINI C. , LEFF P. 
Published: February 2006

ABSTRACT: Recent studies have demonstrated that activation of the same G‐protein coupled receptor can generate different agonist pharmacology depending on the signaling pathway(s) to which it couples. Two types of behavior have been exemplified; differences in affinity order, and differences in efficacy order with the same affinity order. The two‐state model of receptor activation cannot explain these data, since a single active receptor state cannot couple differently to the two response pathways for different ligands. We have therefore extended the two‐state model to a three‐state model in which receptors exist in three states: an inactive state, R, and two different active states, R* and R**.The model has two modes, the ‘intact mode’, in which all the equilibria are linked; and the ‘isolated mode’ in which the two response pathways are isolated from each other, giving effectively two separate two‐state systems. In the ‘intact mode’ the same agonist affinity order is predicted for both response pathways, but a different efficacy order. In the ‘isolated mode’, since the equilibria are no longer linked, the model predicts that a different affinity order may be obtained for the two pathways.Owing to the linkage of all the equilibria in the intact three‐state model the level of constitutive activity through one pathway can affect the direction of agonism through the other pathway, resulting in the conversion of an inverse agonist into a positive agonist. This change in the direction of agonism is also predicted to occur when the two response pathways are isolated.The three‐state model therefore predicts that agonists, acting at the same receptor, may show different affinity orders and different efficacy orders depending upon which response is measured and the assay system used, and also predicts that inverse agonism may be system dependent.
Enzymatic Modification of Natural Compounds with Pharmacological Propertiesa
Authors: RIVA SERGIO , MONTI DANIELI , LUISETTI MONICA , DANIELI BRUNO 
Published: February 2006

Abstract: Glycosides of various classes of natural products are widely distributed in nature, where they are often present esterified with aliphatic and aromatic acids at specific OH's of their sugar moieties.Many of these compounds are pharmacologically important molecules or possess other interesting properties. For instance, ginsenosides (e.g., 3) are therapeutic dammarane‐type oligoglycosides isolated from the water‐soluble portion of the dried roots and leaves of Panax ginseng C.A. Meyer (Araliaceae), a plant widely used in traditional Chinese medicine.In recent years, we have exploited the regioselectivity of lipases and proteases in organic solvents for the synthesis of specific esters of ginsenosides as well as the selectivity of the β‐1,4‐galactosyltransferase from bovine colostrum to obtain new glycosyl derivatives of these compounds.The application of these two enzymatic methodologies has also been exemplified with other natural compounds with pharmacological properties: digitonin (5), colchicoside (6), and flavonoid glycosides.
Production of “Neometalloenzymes” by De Novo Biosynthesis: New ELISA Method for Their Characterization
Authors: NEDONCHELLE E. , LEDUC C. , GARCIA X. , GUZMAN R. , VIJAYALAKSHMI M. A. 
Published: February 2006

Several approaches known for producing “neometalloenzymes” are classified into two categories: protein engineering using antibodies as starting materials and “de novo” biosynthesis of metal‐binding antibodies with potential catalytic metal‐binding structure. This latter approach is chosen in this study. Polyclonal anti‐zinc‐iminodiacetate [IDA‐Zn(II)] antibodies are produced in rabbits and mice. Because of the absolute need for the unequivocal screening of the hapten [IDA‐Zn(II)] specific antibodies, a new ELISA method was developed using a biheaded polyethylene glycol with biotin on one end and the hapten on the other end.The parameters for optimizing the immunization and the ELISA technique are discussed and the method is validated with rabbit and mice sera.
Global Epidemiology of Hemoglobin Disorders
Authors: ANGASTINIOTIS MICHAEL , MODELL BERNADETTE 
Published: February 2006

Abstract: Thalassemias and the hemoglobinopathies such as Hemoglobins S, C and E, are now a global problem. They have spread through migration from their native areas in the Mediterranean, Africa and Asia and are now endemic throughout Europe, the Americas and Australia. Comprehensive control programs in recent years have succeeded in limiting the numbers of new births and prolonging life in affected individuals. Such programs have been successful in a minority of countries and have little global impact. Over 300,000 infants with major syndromes are born every year and the majority die undiagnosed, untreated or under‐treated.Countries may be divided into three general categories according to the services available: A. Endemic Mediterranean countries. In these long‐established prevention programs have succeeded in achieving 80%‐100% prevention. Specialized clinics able to provide optimum treatment. B. Areas of the developed, industrialized world where prevalence is increasing because of migration. These countries have the means to provide adequate control but have problems in reaching immigrant groups with different cultural background. C. Countries of the developing world where the provision of services is hampered by economic difficulties, other health priorities due to high infant mortality from infectious diseases, and religious/cultural constraints.
The Psychosocial Impact of Chronic Illness
Authors: POLITIS CONSTANTINA 
Published: February 2006

Abstract: Depending on the severity of thalassemia and the level of health care provided, the thalassemic person may suffer from his/her chronic condition going through the path: disease → impairment → disability → handicap. There is evidence that a high clinical burden is associated with a psychosocial burden for the patients and the family.In Greece, support strategies have developed in the last twenty years to help the thalassemic patient and his/her family. Recent studies in 909 patients show that the life span is prolonged (mean age 27 years), 83% of the patients study or work, 12% are married and 2.3% have set up a family, and 98% utilize the social benefits provided (free education, free entrance to universities, tax allowances, cash benefit, early retirement, etc.). However, psychometric tests performed in 131 patients and 65 matched normal controls over 14 years of age have shown that hostility (extroverted, delusional, total p < 0.001) is an important component of the psychological profile of the patients.The patient's role through their association is strong and undoubtedly has influenced the public's extremely high (93%) awareness of the basic features of the disease and the supportive attitude of the average Greek citizen toward the life style of the thalassemic patient. On the whole, in many thalassemic patients illness has overpowered all other aspects of life. For few, however, life is much more than an illness. Shouldn't this be the message for the patient's psychosocial support strategies?
New Aspects of Chemoreception in Flies
Authors: HANSEN KAI , WACHT SUSANNE , SEEBAUER HELGA , SCHNUCH MARIANNE 
Published: February 2006

ABSTRACT: For studies of insect taste the sensory cells of labellar taste hairs on the proboscis of calliphorid flies (e.g., Phormia) are preferred objects. Three sensory cells are electrophysiologically characterized: a sugar cell, a water cell and a cation or salt cell. Studying hairs on legs and proboscis of other families of flies we recently obtained results that extend our knowledge about the complexity of food detection in flies.The hoverfly Eristalis tenax (Syrphidae family) feeds on nectar and pollen of flowers. While nectar is recognized via the sugar cell, the so‐called salt cell is activated by low concentrations of a water‐soluble substance in extracts of pollen. From several tested pollen constituents only proline, an essential amino acid for pollen germination, stimulates the salt cell. The discrimination between salt and pollen in behavioral tests can be explained by the finding that the water cell remains active in the presence of pollen extract, but is inhibited by salts. Obviously the water cell activity is involved in the feeding decision. We already described a similar situation in Phormia, where the salt cell activity only elicits feeding behavior when the water cell is active too.In contrast to the sugar cells of species of flies studied so far the sugar cell of the house fly Musca domestica (Muscidae family) is highly sensitive to lactose, a disaccharide (β‐galactoside (1→4) glucoside) naturally occurring only in the milk of mammals. Thus sugar spectra adapt to special environmental food situations.The fifth tarsomere of the forelegs of Musca bears besides two D‐hairs 46 hairs of the B‐type. The B‐hairs are functionally not uniform in contrast to their structural identity. Only two hairs, the 'water hairs,' contain a water cell beside a spontaneously firing cell, but no sugar cell. Other examples of diversity are hairs that contain apart from the classical sugar cells, additional cells which react either to p‐nitrophenyl‐β‐galactoside, but not to the chemically related lactose, or to p‐nitrophenyl‐α‐glucoside. Therefore the rule established for the labellar taste hairs that each hair type contains the same physiological equipment of sensory cells, does not hold for the taste hairs of the legs.
Molecular Cloning and Taste Bud‐Specific Expression of a Novel Cyclic Nucleotide‐Gated Channel
Authors: MISAKA TAKUMI , KUSAKABE YUKO , EMORI YASUFUMI , ARAI SOICHI , ABEA KEIKO 
Published: February 2006

ABSTRACT: Cyclic nucleotide‐gated (CNG) channels serve as downstream targets of signaling pathways in vertebrate photoreceptor cells and olfactory sensory neurons. For taste signaling as well, a great deal of information is available predicting the presence of a CNG channel, but no report has been presented on its molecular entity. Here we report on molecular cloning and functional expression of a taste bud‐specific CNG channel tentatively named CNGgust.Reverse transcriptase polymerase chain reaction (RT‐PCR) primers were synthesized according to some amino acid sequences generally conserved in many CNG channels. RT‐PCR was conducted using rat circumvallate papillary mRNA‐derived cDNA as a template to obtain positive clones. A corresponding genomic DNA clone was then obtained by screening from a genomic DNA library. Dissecting the entire structure of this gene, we found that the encoding protein had an amino acid sequence similarity of 80% to each of retina and olfactory CNG channels. It was also found by immunostaining with a specific antibody that this gustatory CNG channel (CNGgust) is localized in the tongue and also expressed specifically on the pore side of each taste bud in the circumvallate papillae. Electrophysiological experiments demonstrated that CNGgust resided in a functional state.All these data suggest that CNGgust may be involved in taste signal transduction in sensory cells.
The Influence of Ensheathing Cells on Olfactory Receptor Cell Neurite Outgrowth In Vitroa
Authors: KAFITZ KARL W. , GREER CHARLES A. 
Published: February 2006

ABSTRACT: We previously reported that laminin substrates increased primary (1°) neurite outgrowth from olfactory receptor cells (ORCs) in vitro.5 To further explore mechanisms underlying the outgrowth of ORC neurites, we have cocultured ORCs with the ensheathing cells (ENSH) from the olfactory nerve.ORCs were plated either: (i) directly on monolayers of ENSH (prepared with minor modifications as reported by Doucette and Devon,8 or (ii) on coverslips suspended above the ENSH monolayer to investigate diffusible trophic influences of ENSH. In addition, ORCs were cocultured with either olfactory bulb glia (OBG) or hippocampal astrocytes (HG) or grown on either laminin (LN) substrates or poly‐l‐lysine (PLL) controls. The length of ORC neurites was determined after 48 hr in vitro. Immunocytochemical characterization of the ENSH cultures for p75 nerve growth factor (NGF) receptor and glial fibrillary acidic protein (GFAP) revealed that those cultures contained more than 80% ENSH. In OBG cultures ~10% and in HG cultures no cells with ENSH characteristics were found. All cells with ENSH characteristics were also LN‐immunoreactive. After 48 hr in culture ORCs had the longest 1° neurites when they were cocultured with ENSH. No significant differences in the 1° neurite length were found comparing ORCs grown directly on ENSH and ORCs physically separated from ENSH. ORCs cultured on HG and on EHS‐LN showed no significant differences in the ORC 1° neurite length, but on both substrates the ORC 1° neurites were significantly shorter than on ENSH. The length of the ORC secondary neurites did not vary significantly in the different culture conditions. Our results suggest that while LN appears to contribute to ORC neurite extension, additional diffusible factors released from ENSH are likely to be further determinants of neurite outgrowth. Because the OBG and HG cocultures did not influence ORC neurite outgrowth as significantly as did the ENSH, it seems plausible to suggest that these diffusible factors may be specific to subpopulations of glial cells.
On the Nature of Mammalian and Human Pheromones
Authors: McCLINTOCK MARTHA K. 
Published: February 2006

ABSTRACT: Communication by chemical (Pheromone) signals is important in many species, including mammals. Chemosensory and hormonal systems can interact in at least two ways: (i) chemosensory input, especially but not exclusively that through the vomeronasal organ, may elicit hormonal release, which, in turn, may facilitate behavioral or physiological responses; and (ii) hormones, especially steroids, may be essential for some responses to chemosensory, including vomeronasal, input. Recent, still controversial reports, suggest that chemosensory communication may occur in humans via a residual vomeronasal organ and that chemosensory/hormonal interactions also operate in humans.In this symposium these matters are examined critically. Johnston explores the concept of Pheromone communication and suggests that the notion of a single‐chemical 'magic bullet' irresistably leading to a preprogrammed result is too simplistic despite documented examples of special stimuli acting via the vomeronasal organ. Meredith briefly reviews evidence for hormonal mediation of the effects of vomeronasal input; including a situation where vomeronasal and hormonal facilitation of a behavior appear to be interchangable‐but where vomeronasal input appears important only in inexperienced animals. Wood discusses evidence that the effectiveness of chemosensory input to particular brain nuclei depends critically on the simultaneous presence of a steroid hormone within the same nucleus. Monti‐Bloch presents his evidence that steroids may act as gender‐specific chemical signals in humans, exciting an electrical response from the residual human vomeronasal organ and affecting human hormone levels.
fMRI Study of Taste Cortical Areas in Humans
Authors: Faurion Annick , Cerf Barbara , Le Bihan Denis , Pilliasa Anne‐Marie 
Published: February 2006

ABSTRACT: We used 3 Tesla functional magnetic resonance imaging (fMRI) with echo planar imaging to map taste projections in the human. Activations were found surrounding and buried in the sylvian fissure; the upper part of insula, the frontal operculum, and the foot of the pre‐ and postcentral gyri were usually activated. Moreover, we could describe, for the first time, a lateralized associative projection located in the lower part of the dominant hemisphere of the subject (n= 10). We also observed activations in the anterior cingulate gyrus, the centromedial thalamus, and other areas related to emotional or cognitive processes.Thirty subjects were submitted to a familiarization experiment sampling neophobic and nonneophobic stimuli. Measurements of isointense concentrations, magnitude estimates and hedonic values were assessed repetitively for 10 weeks. Five subjects performed 3 fMRI experiments, before, during and after familiarization.Psychophysical data showed a relationship between the evolution of the hedonic assessment and the intensity of the perception, and fMRI results showed a relationship between the evolution of the hedonic assessment and the evolution of the percent of activated pixels in taste cortical area.
Human Brain Function during Odor Encoding and Recognition: A PET Activation Studya
Authors: DADE L. A. , JONES‐GOTMAN M. , ZATORRE R. J. , EVANS A. C. 
Published: February 2006

ABSTRACT: In previous positron emission tomography (PET) studies we have shown significant regional cerebral blood flow (rCBF) increases during olfactory stimulation: unilaterally in the right orbitofrontal cortex, and bilaterally in the inferior frontal and temporal lobes (piriform cortex). In the present study we investigated brain function during different stages of olfactory memory processing.Subjects were scanned during four tasks: odor encoding, long‐term odor recognition, short‐term odor recognition and a no‐odor sensorimotor control task. Subjects were 12 right‐handed healthy volunteers (6 men, 6 women). Each subject underwent a training session four days prior to their PET scan to learn the six odors required for the long‐term memory scan. PET scans were obtained with a Siemens Exact ECAT HR+ 3D system using H215O methodology and 60‐sec scanning intervals. PET images were coregis tered with each subject's magnetic resonance imaging scan, averaged, and transformed into standard stereotaxic space. Paired image subtractions were analyzed for rCBF changes.Preliminary analyses have revealed significant activation of the right orbitofrontal region and bilateral piriform cortices during the long‐term odor recognition task compared with the control task. Activation of the right piriform cortex was present during the short‐term recognition task. Brain activity during encoding and retrieval tasks also involved prefrontal corti ces. PET activation studies of memory in other modalities have led to hypotheses of a hemispheric encoding/retrieval asymmetry in frontal cortex; the generalizability of this theory to olfactory memory will be discu ssed.
Draize Eye Scores and Eye Irritation Thresholds in Man Can Be Combined into One QSARa
Authors: ABRAHAM MICHAEL H. , KUMARSINGH RACHEL , COMETTO‐MUÑIZ J.ENRIQUE , CAIN WILLIAM S. 
Published: February 2006

ABSTRACT: Draize eye scores (DES) of 37 pure organic liquids have been converted into scores for the corresponding vapors, DES/P0, where P0 is the liquid vapor pressure in atmospheres at 298 K. It is shown that there is a constant difference of 6.7 between values of log(DES/P0) and log (1/EIT), where EIT is the eye irritation threshold in parts per million (ppm, by volume) of eight vapors for human subjects. The 37 log(DES/P0) values can be combined with log(1/EIT) values for 17 vapors into one quantitative structure‐activity relationship (QSAR) for sensory potency (SP) using our general solvation equation,Equation 1

image
where R2 is an excess molar refraction, π2H the compound polarizability/dipolarity, Σα2H and Σβ2H are the compound hydrogen‐bond acidity and basicity, and L16 is the gas‐hexadecane partition coefficient at 298 K. n is the number of data points, r the correlation coefficient, SD the standard deviation, and F the F‐statistic. LogSP is then either [log(DES/P0) ‐ 0.66] or log (1/EIT), confirming the result for the eight common compounds. It is suggested that the equation can be used to predict eye irritancy of organic vapors and pure liquids. It is further suggested that for the compounds in the data set, the main process in eye irritation is transfer of the compound from the vapor or pure liquid to a biological phase, and a number of chemical properties of the biological phase have been mapped out through the equation. These properties are consistent with corresponding properties for a number of organic liquid phases.