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Molecular Nature (molecular + nature)
Selected AbstractsUnderstanding heart development and congenital heart defects through developmental biology: A segmental approachCONGENITAL ANOMALIES, Issue 4 2005Masahide Sakabe ABSTRACT The heart is the first organ to form and function during development. In the pregastrula chick embryo, cells contributing to the heart are found in the postero-lateral epiblast. During the pregastrula stages, interaction between the posterior epiblast and hypoblast is required for the anterior lateral plate mesoderm (ALM) to form, from which the heart will later develop. This tissue interaction is replaced by an Activin-like signal in culture. During gastrulation, the ALM is committed to the heart lineage by endoderm-secreted BMP and subsequently differentiates into cardiomyocyte. The right and left precardiac mesoderms migrate toward the ventral midline to form the beating primitive heart tube. Then, the heart tube generates a right-side bend, and the d-loop and presumptive heart segments begin to appear segmentally: outflow tract (OT), right ventricle, left ventricle, atrioventricular (AV) canal, atrium and sinus venosus. T-box transcription factors are involved in the formation of the heart segments: Tbx5 identifies the left ventricle and Tbx20 the right ventricle. After the formation of the heart segments, endothelial cells in the OT and AV regions transform into mesenchyme and generate valvuloseptal endocardial cushion tissue. This phenomenon is called endocardial EMT (epithelial-mesenchymal transformation) and is regulated mainly by BMP and TGF,. Finally, heart septa that have developed in the OT, ventricle, AV canal and atrium come into alignment and fuse, resulting in the completion of the four-chambered heart. Altered development seen in the cardiogenetic process is involved in the pathogenesis of congenital heart defects. Therefore, understanding the molecular nature regulating the ,nodal point' during heart development is important in order to understand the etiology of congenital heart defects, as well as normal heart development. [source] Fly Six-type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye developmentDEVELOPMENTAL DYNAMICS, Issue 3 2005Kristy L. Kenyon Abstract Two members from the Six class of homeobox transcription factors, Sine oculis (SO) and Optix, function during development of the fly visual system. Differences in gain-of-function phenotypes and gene expression suggest that these related factors play distinct roles in the formation of the fly eye. However, the molecular nature of their functional differences remains unclear. In this study, we report the identification of two novel factors that participate in specific partnerships with Sine oculis and Optix during photoreceptor neurons formation and in eye progenitor cells. This work shows that different cofactors likely mediate unique functions of Sine oculis and Optix during the development of the fly eye and that the repeated requirement for SO function at multiple stages of eye development reflects the activity of different SO,cofactor complexes. Developmental Dynamics 234:497,504, 2005. © 2005 Wiley-Liss, Inc. [source] Ligand binding of leukocyte integrin very late antigen-4 involves exposure of sulfhydryl groups and is subject to redox modulationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Si-Yen Liu Abstract Activation of leukocyte integrins is important for selective recruitment of cells from the circulation to tissues. Our previous studies showed that the binding between the integrin very late antigen-4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1) is modulated by reactive oxygen species. In this study, we investigated the molecular nature of redox modulation on the activation states of VLA-4 on human leukocytes. We found that ligand binding of VLA-4 induced exposure of sulfhydryl groups on the ,4 peptide. Low concentrations (5,10,µM) of exogenous hydrogen peroxide in the presence or absence of added glutathione enhanced the ligand binding ability of VLA-4 to VCAM-1 and cell rolling on VCAM-1, while higher concentrations (,100,µM) of hydrogen peroxide inhibited the binding. Exogenous hydrogen peroxide and glutathione induced molecular modification of S -glutathionylation on the ,4 peptide. The redox regulation of the VLA-4 binding activity required outside-in signaling and cytoskeleton rearrangement. Our results indicate that ligand binding of VLA-4 involves redox modulations which may play a pivotal role in regulating the activation states of VLA-4 in inflammatory tissues and hence direct leukocyte trafficking. [source] The molecular composition of soil organic matter as determined by 13C NMR and elemental analyses and correlation with pesticide sorptionEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 6 2006R. Ahmad Summary Although the chemical composition of soil organic matter (SOM) is known to significantly influence sorption of pesticides and other pollutants, it has been difficult to determine the molecular nature of SOM in situ. Here, using 13C nuclear magnetic resonance (NMR) data and elemental composition in a molecular mixing model, we estimated the molecular components of SOM in 24 soils from various agro-ecological regions. Substantial variations were revealed in the molecular nature of SOM. As a proportion of soil carbon the proportion of the carbonyl component ranged from 0.006 to 0.05, charcoal from 0 to 0.15, protein from 0.09 to 0.29, aliphatic from 0.14 to 0.30, carbohydrate from 0.21 to 0.31, and lignin from 0.05 to 0.42. The relationships between Koc (sorption per unit mass of organic carbon) of carbaryl (1-naphthyl methylcarbamate) and phosalone (S- 6-chloro-2,3-dihydro-2-oxobenzoxazol-3-ylmethyl O,O -diethyl phosphorodithioate) and the molecular nature of organic matter in the soils were significant. Of the molecular components estimated, lignin and charcoal contents correlated best with sorption of carbaryl and phosalone. Aliphatic, carbohydrate and protein contents were found to be negatively correlated with the Koc of both pesticides. The study highlights the importance of the molecular nature of SOM in determining sorption affinities of non-ionic pesticides and presents an indirect method for sorption estimation of pesticides. [source] Chemical bonding in ternary magnesium hydridesINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3 2003Emilio Orgaz Abstract The electronic structure of various alkali and alkaline,earth magnesium-based hydrides was investigated in detail. These types of crystalline compounds show MgH4 or MgH6 units ordered within a light-metal framework. We investigated the nature of the chemical bonding in these units by means of quantum chemical calculations of several related clusters. The properties of the charge density of the clusters, within the framework of the theory of atoms in molecules, was analyzed. A further set of computations of the band structure of the solid hydrides was conducted using a state-of the-art density functional-based method and the mechanism of stabilization of the MgH units is discussed. It was found that the properties obtained at the molecular level correlate well with those of the solid crystals, indicating the molecular nature of the extended systems in which the units MgHx, x = 4, 6, are stabilized by means of MgH closed-shell interactions. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 150,164, 2003 [source] Florigen: One Found, More to Follow?JOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 6 2006Xuhong Yu Abstract Florigen(s) are molecules that are synthesized in response to appropriate photoperiods and transmitted from leaves to shoot apices to promote floral initiation. It has been recently discovered in Arabidopsis that mRNA of the FT gene acts as a florigen. In Arabidopsis, cryptochromes and phytochromes mediate long-day promotion of CO protein expression, which activates FT mRNA expression in leaves. FT mRNA is transmitted to the shoot apex, where it acts together with FD to activate transcription of floral meristem identity genes, resulting in floral initiation. The discovery of the molecular nature of a florigen was a major scientific breakthrough in 2005. (Managing editor: Li-Hui Zhao) [source] The development of PET radioligands for imaging the translocator protein (18,kDa): What have we learned?JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2010Christopher Luus Abstract The translocator protein (TSPO; 18,kDa), formerly known as the peripheral benzodiazepine receptor (PBR), is minimally expressed in the healthy brain. On the other hand, increased levels of TSPO have been noted in brain disorders for which an immune response is elicited. This increase in TSPO expression has been reported to coincide with the process of microglial activation making the measurement of TSPO density a useful indicator of active brain disease. To this end several new classes of TSPO positron emission tomography radioligands have been developed and evaluated. However, the incomplete pharmacological characterization of the TSPO and its ligands as well as differences in pathophysiology, pharmacology and molecular nature across species and tissue types means that caution must be exercised when comparing data obtained with various TSPO radioligands. A re-evaluation of our interpretation of imaging data, which better correlates with our current understanding of TSPO pharmacology in disease, requires consideration. Copyright © 2010 John Wiley & Sons, Ltd. [source] CDNA microarray analysis of gene expression in fibroblasts of patients with x-linked Emery,Dreifuss muscular dystrophyMUSCLE AND NERVE, Issue 6 2002Toshifumi Tsukahara PhD Abstract To clarify the molecular nature of the pathogenesis in X-linked Emery,Dreifuss muscular dystrophy (EDMD), we monitored the expression of 2400 genes in control and EDMD fibroblasts by using complementary DNA (cDNA) microarray techniques. A total of 60 genes whose expression was altered in EDMD fibroblasts when compared with control fibroblasts were identified. Twenty-eight genes whose expression was altered with the emerin deficiency were rescued by infection with a recombinant adenovirus expressing emerin. The altered expression in five genes, including the lamin A/C gene, was confirmed by reverse transcription,polymerase chain reaction. Our preliminary results suggest a correlation between disease similarity and gene expression. We conclude that the cDNA microarray is a very efficient tool to clarify genetic and pathological features of diseases. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 898,901, 2002 [source] Replacing the rod with the cone transducin , subunit decreases sensitivity and accelerates response decayTHE JOURNAL OF PHYSIOLOGY, Issue 17 2010C.-K. Chen Cone vision is less sensitive than rod vision. Much of this difference can be attributed to the photoreceptors themselves, but the reason why the cones are less sensitive is still unknown. Recent recordings indicate that one important factor may be a difference in the rate of activation of cone transduction; that is, the rising phase of the cone response per bleached rhodopsin molecule (Rh*) has a smaller slope than the rising phase of the rod response per Rh*, perhaps because some step between Rh* and activation of the phosphodiesterase 6 (PDE6) effector molecule occurs with less gain. Since rods and cones have different G-protein , subunits, and since this subunit (T,) plays a key role both in the interaction of G-protein with Rh* and the activation of PDE6, we investigated the mechanism of the amplification difference by expressing cone T, in rod T,-knockout rods to produce so-called GNAT2C mice. We show that rods in GNAT2C mice have decreased sensitivity and a rate of activation half that of wild-type (WT) mouse rods. Furthermore, GNAT2C responses recover more rapidly than WT responses with kinetic parameters resembling those of native mouse cones. Our results show for the first time that part of the difference in sensitivity and response kinetics between rods and cones may be the result of a difference in the G-protein , subunit. They also indicate more generally that the molecular nature of G-protein , may play an important role in the kinetics of G-protein cascades for metabotropic receptors throughout the body. [source] Cytoplasmic calcium oscillations and store-operated calcium influxTHE JOURNAL OF PHYSIOLOGY, Issue 13 2008James W. Putney Intracellular calcium oscillations have fascinated scientists for decades. They provide an important cellular signal which, unlike most signalling mechanisms, is digitally encoded. While it is generally agreed that oscillations most frequently arise from cyclical release and re-uptake of intracellularly stored calcium, it is becoming increasingly clear that influx of calcium across the plasma membrane also plays a critical role in their maintenance and even in delivering their signal to the correct cellular locus. In this review we will discuss the role played by Ca2+ entry mechanisms in Ca2+ oscillations, and approaches to understanding the molecular nature of this Ca2+ entry pathway. [source] Constitutive activation of a CC-NB-LRR protein alters morphogenesis through the cytokinin pathway in ArabidopsisTHE PLANT JOURNAL, Issue 1 2008Kadunari Igari Summary Possible links between plant defense responses and morphogenesis have been postulated, but their molecular nature remains unknown. Here, we introduce the Arabidopsis semi-dominant mutant uni-1D with morphological defects. UNI encodes a coiled-coil nucleotide-binding leucine-rich-repeat protein that belongs to the disease resistance (R) protein family involved in pathogen recognition. The uni-1D mutation causes the constitutive activation of the protein, which is stabilized by the RAR1 function in a similar way as in other R proteins. The uni-1D mutation induces the upregulation of the Pathogenesis-related gene via the accumulation of salicylic acid, and evokes some of the morphological defects through the accumulation of cytokinin. The rin4 knock-down mutation, which causes the constitutive activation of two R proteins, RPS2 and RPM1, induces an upregulation of cytokinin-responsive genes and morphological defects similar to the uni-1D mutation, indicating that the constitutive activation of some R proteins alters morphogenesis through the cytokinin pathway. From these data, we propose that the modification of the cytokinin pathway might be involved in some R protein-mediated responses. [source] Complex nature of the human antisperm antibody response in SCID miceANDROLOGIA, Issue 2 2004M. Kurpisz Summary. Human peripheral blood mononuclear (PBMs) cells were introduced into the peritoneal cavity of severely-combined immunodeficient (SCID) mice in concentrations of 2.5,4.0 × 107 cells per mouse. Whole mononuclear cell suspensions were used either unstimulated or following primary in vitro culture with human spermatozoa. In some experiments, immunodepletion of CD8+ cells was carried out prior to grafting. Lymphocytes were obtained from nonsensitized (to antigen) human subjects or from individuals who were primed in vivo (vasectomized individuals in case of sperm antigens). An enzyme-linked immunosorbent assay was employed to assess total human immunoglobulin (G or M) levels as well as the specificity of the antibodies generated. We have been successful by generating primary and secondary immune responses with ,naïve' human lymphocytes, challenged with chlamydia or ovalbumin but without adjuvant or CD8+ immunodepletion; however, we were unable to induce specific antibodies to spermatozoa under this regime in SCID male mice. We then employed female SCID mice, treated with sperm antigen extracts (glycosylated or deglycosylated) encapsulated in liposomes and human lymphocytes obtained from ,naïve' or pre-sensitized in vivo subjects. It was found that the most pronounced humoral response to sperm antigens was obtained with deglycosylated antigens and PBMs from vasectomized (in vivo pre-primed to spermatozoa) individuals. A presented SCID mice model can be helpful at understanding of antisperm antibody development and the molecular nature of generated antibodies to modified sperm antigenic entities. [source] Pho d 2, a major allergen from date palm pollen, is a profilin: cloning, sequencing, and immunoglobulin E cross-reactivity with other profilinsCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2005J. A. Asturias Summary Background Up to now, some date palm pollen (DPP) allergens have been described but very few data are available about their molecular nature. The aim of this study was to identify and characterize Pho d 2, a major allergen from this pollen. Methods Sera from 25 patients allergic to DPP were analysed by immunoblotting. Purification of DPP profilin was performed by poly- l -proline affinity chromatography. Profilin-encoding cDNA from DPP was cloned by using a RT-PCR strategy and recombinant allergen was expressed as a non-fusion protein in Escherichia coli. Natural and recombinant Pho d 2 were investigated by means of enzyme allergosorbent test to compare the immunologic properties of both allergens and to analyse cross-reactivity with other profilins. Results A 14.4 kDa protein was identified as a major allergen in DPP extract. Purification, cloning, heterologous expression, and inhibition experiments identified it as profilin (Pho d 2). Pho d 2 comprises 131 amino acids and has high sequence identity with other allergenic food and pollen profilins. The prevalence of specific IgE antibody reactivity to natural Pho d 2 by ELISA was 56% and 64% by skin prick test (SPT). Pho d 2 is an important allergen as it is responsible for more than 70% of the IgE reactivity to the pollen extract. IgE directed against Pho d 2 showed a strong cross-reactivity with other profilins such as those from olive tree and grass pollens. Conclusion Pho d 2, a 14.4 kDa protein identified as profilin, is a major and relevant allergen in DPP, as confirmed by SPT and thereby may elicit clinical symptoms in sensitized patients. [source] WHAT MAKES A CGRP2 RECEPTOR?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007DL Hay SUMMARY 1Heterogeneity in the receptors for the neuropeptide calcitonin gene-related peptide (CGRP) has been apparent for nearly 20 years. This is most clearly manifested in the observation of CGRP8,37 -sensitive and -insensitive populations of CGRP-activated receptors. The pA2 values for CGRP8,37 in excess of 7 are widely considered to be the result of antagonism of CGRP1 receptors, whereas those below 7 are believed to be the consequence of antagonism of a second population of receptors, namely CGRP2 receptors. 2However, a multitude of pA2 values exist for CGRP8,37, spanning several log units, and as such no obvious clusters of values are apparent. Understanding the molecular nature of the receptors that underlie this phenomenon is likely to aid the development of selective pharmacological tools to progress our understanding of the physiology of CGRP and related peptides. Because there is active development of CGRP agonists and antagonists as therapeutics, such information would also further this pursuit. 3The CGRP1 receptor is pharmacologically and molecularly well defined as a heterodimer of the calcitonin receptor-like receptor (CL) and receptor activity modifying protein (RAMP) 1. The CL/RAMP1 complex is highly sensitive to CGRP8,37. Conversely, the constituents of the CGRP2 receptor have not been identified. In fact, there is little evidence for a distinct molecular entity that represents the CGRP2 receptor. 4Recent pharmacological characterization of receptors related to CGRP1 has revealed that some of these receptors may explain CGRP2 receptor pharmacology. Specifically, AMY1(a) (calcitonin receptor/RAMP1) and AM2 (CL/RAMP3) receptors can be activated by CGRP but are relatively insensitive to CGRP8,37. 5This, along with other supporting data, suggests that the ,CGRP2 receptor' that has been extensively reported in the literature may, in fact, be an amalgamation of contributions from a variety of CGRP-activated receptors. The use of appropriate combinations of agonists and antagonists, along with receptor expression studies, could allow such receptors to be separated. [source] Cystic kidney diseases and planar cell polarity signalingCLINICAL GENETICS, Issue 2 2009RL Bacallao Renal cystic diseases are a major clinical concern as they are the most common genetic cause of end-stage renal disease. While many of the genes causing cystic disease have been identified in recent years, knowing the molecular nature of the mutations has not clarified the mechanisms underlying cyst formation. Recent research in model organisms has suggested that cyst formation may be because of defective planar cell polarity (PCP) and/or ciliary defects. In this review, we first outline the clinical features of renal cystic diseases and then discuss current research linking our understanding of cystic kidney disease to PCP and cilia. [source] | ||||||||||||||||