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Cleft
Kinds of Cleft Terms modified by Cleft Selected AbstractsRock Around the Clock in the Middle Ear CleftTHE LARYNGOSCOPE, Issue 6 2002Sady Selaimen da Costa MD First page of article [source] Water Accessibility to the Binding Cleft as a Major Switching Factor from Entropy-Driven to Enthalpy-Driven Binding of an Alkyl Group by Synthetic ReceptorsCHEMISTRY - AN ASIAN JOURNAL, Issue 5 2010Sayaka Matsumoto Abstract Free energy, enthalpy, and entropy changes in the binding of alkyl pyridines to water-soluble zinc porphyrin receptors with varying accessibility of water to the binding cleft were determined to explain why the driving force of hydrophobic effects is enthalpic in some occasions and entropic in others. Zinc porphyrins bearing four alkyl pillars with terminal solubilizing poly(oxyethylene) (POE) chains of molecular weight of 750 (1), with eight alkyl pillars with terminal solubilizing POE chains of molecular weight of 350 (3), and with eight alkyl pillars with POE of molecular weight of 750 (4) had a binding cleft with decreasing water accessibility in this order as revealed by binding selectivity of imidazole/pyridine. Although all these porphyrins showed that the free energy of binding (,,Go) increases linearly as the alkyl group of the guest is lengthened (,,Go per CH2 was 2.6, 2.8, and 2.6,kJ,mol,1 for 1, 3, and 4, respectively), the origin of the free energy gain was much different. Receptor 1 with the most hydrophilic binding site bound the alkyl group by an enthalpic driving force (4-pentylpyridine favored over 4-methylpyridine by ,,Ho=,16.4,kJ,mol,1), while receptor 4 with the most hydrophobic binding site by an entropic driving force (4-pentylpyridine favored over 4-methylpyridine by ,,So=39.6,J,K,1,mol,1). Receptor 3 showed intermediate behavior: both enthalpic and entropic terms drove the binding of the alkyl group with the enthalpic driving force being dominant. The binding site of the four-pillared receptor (1) is open and accessible to water molecules, and is more hydrophilic than that of the eight-pillared receptor (4). We propose that the alkyl chains of 1 are exposed to water to produce a room to accommodate the guest to result in enthalpy-driven hydrophobic binding, whereas 4 can accommodate the guest without such structural changes to lead to entropy-driven hydrophobic binding. Therefore, accessibility of water or exposure of the binding site to the water phase switches the driving force of hydrophobic effects from an entropic force to an enthalpic force. [source] Genes causing clefting syndromes as candidates for non-syndromic cleft lip with or without cleft palate: a family-based association studyEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2008Luca Scapoli Clefts of the orofacial region are among the most common congenital defects, caused by abnormal facial development during gestation. Non-syndromic cleft lip with or without cleft palate (NSCLP) is a complex trait most probably caused by multiple interacting loci, with possible additional environmental factors. As facial clefts form part of more than 300 syndromes, one strategy for identifying the genetic causes of NSCLP could be to study candidate genes responsible for clefting syndromes. Three genes were selected for this investigation: TP63, which codes for the tumour protein p63 and causes Ectrodactyly-Ectodermal dysplasia-orofacial Cleft syndrome; JAG2, a downstream gene of TP63; and MID1, which is responsible for Opitz syndrome. A linkage disequilibrium investigation was performed with intragenic single nucleotide polymorphisms on each of these genes in a sample study of 239 patients/parents trios. Evidence which suggests that JAG2 and MID1 may play a role in NSCLP was obtained. [source] Functions of glutamate transporters in cerebellar Purkinje cell synapsesACTA PHYSIOLOGICA, Issue 1 2009Y. Takayasu Abstract Glutamate transporters play a critical role in the maintenance of low extracellular concentrations of glutamate, which prevents the overactivation of post-synaptic glutamate receptors. Four distinct glutamate transporters, GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3 and EAAT4, are distributed in the molecular layer of the cerebellum, especially near glutamatergic synapses in Purkinje cells (PCs). This review summarizes the current knowledge about the differential roles of these transporters at excitatory synapses of PCs. Data come predominantly from electrophysiological experiments in mutant mice that are deficient in each of these transporter genes. GLAST expressed in Bergmann glia contributes to the clearing of the majority of glutamate that floods out of the synaptic cleft immediately after transmitter release from the climbing fibre (CF) and parallel fibre (PF) terminals. It is indispensable to maintain a one-to-one relationship in synaptic transmission at the CF synapses by preventing transcellular glutamate spillover. GLT-1 plays a similar but minor role in the uptake of glutamate as GLAST. Although the loss of neither GLAST nor GLT-1 affects cerebellar morphology, the deletion of both GLAST and GLT-1 genes causes the death of the mutant animal and hinders the folium formation of the cerebellum. EAAT4 removes the low concentrations of glutamate that escape from uptake by glial transporters, preventing the transmitter from spilling over into neighbouring synapses. It also regulates the activation of metabotropic glutamate receptor 1 (mGluR1) in perisynaptic regions at PF synapses, which in turn affects mGluR1-mediated events including slow EPSCs and long-term depression. No change in synaptic function is detected in mice that are deficient in EAAC1. [source] Cellular dynamics of epithelial clefting during branching morphogenesis of the mouse submandibular glandDEVELOPMENTAL DYNAMICS, Issue 6 2010Yuichi Kadoya Abstract We cultured the rudimental submandibular gland (SMG) of mice with a non,cell-permeable fluorescent tracer, and observed cell behavior during epithelial branching morphogenesis using confocal time-lapse microscopy. We traced movements of individual cells as shadowgraph movies. Individual epithelial cells migrated dynamically but erratically. The epithelial cleft extended by wiggling and separated a cluster of cells into two buds during branching. We examined the ultrastructure of the clefts in SMG rudiments treated with the laminin peptide A5G77f, which induces epithelial clefting. A short cytoplasmic shelf with a core of microfilaments was found at the deep end of the cleft. We propose that epithelial clefting involves a dynamic movement of cells at the base of the cleft, and the formation of a shelf within a cleft cell. The shelf might form a matrix attachment point at the base of the cleft with a core of microfilaments driving cleft elongation. Developmental Dynamics 239:1739,1747, 2010. © 2010 Wiley-Liss, Inc. [source] Mechanisms of substrate transport-induced clustering of a glial glutamate transporter GLT-1 in astroglial,neuronal culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Takayuki Nakagawa Abstract Glutamate uptake by the Na+ -dependent glutamate transporter GLT-1, which is predominantly expressed in astrocytes, is crucial for regulating glutamate concentration at the synaptic cleft and achieving proper excitatory neurotransmission. A body of evidence suggests that GLT-1 constitutively traffics between the plasma membrane and endosomes via an endocytosis/recycling pathway, and forms a cluster. Here, we report substrate transport via GLT-1-induced formation of GLT-1 cluster accompanied by intracellular trafficking in rat astroglial,neuronal cultures. We constructed a recombinant adenovirus expressing enhanced green fluorescence protein (EGFP)-tagged GLT-1. Adenoviral infection resulted in the expression of functional GLT-1,EGFP preferentially in astrocytes, partly as clusters. Treatment with glutamate, but not N -methyl-D-aspartate, dramatically increased the number of GLT-1 clusters within 1 h. The estimated EC50 value of glutamate was 240 ,m. In addition, glutamate decreased the cell surface expression and increased the intracellular expression of GLT-1. The GLT-1 clusters were found in early and recycling endosomes and partly in lysosomes, and were inhibited by blockade of endocytotic pathways. Ionotropic and metabotropic glutamate receptor antagonists had no effect on glutamate-induced GLT-1 clustering. The non-transportable glutamate uptake inhibitors (2S,3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate and dihydrokainate, as well as Na+ -free conditions, prevented the glutamate-induced GLT-1 clustering, whereas the competitive substrates, aspartate and L- trans -pyrrolidine-2,4-dicarboxylate, induced GLT-1 clustering. Furthermore, the Na+/K+ -ATPase inhibitor, ouabain, and the Na+ ionophores, gramicidin and monensin, produced GLT-1 clustering. Modulators of intracellular Ca2+signaling or membrane depolarization had no effect on GLT-1 clustering. Taken together, these results suggest that Na+ influx associated with GLT-1 substrate transport triggers the formation of GLT-1 clusters accompanied by intracellular trafficking via endocytotic pathways in astrocytes. [source] Regulated recycling and plasma membrane recruitment of the high-affinity choline transporterEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Fabiola M. Ribeiro Abstract The high-affinity choline transporter (CHT1) is responsible for uptake of choline from the synaptic cleft and supplying choline for acetylcholine synthesis. CHT1 internalization by clathrin-coated vesicles is proposed to represent a mechanism by which high-affinity choline uptake can be modulated. We show here that internalized CHT1 is rapidly recycled back to the cell surface in both human embryonic kidney cells (HEK 293 cells) and SH-SY5Y neuroblastoma cells. This rapidly recycling pool of CHT1 comprises about 10% of total CHT1 protein. In the SH-SY5Y neuroblastoma cell line K+ -depolarization promotes Ca2+ -dependent increase in the rate of CHT1 recycling to the plasma membrane without affecting the rate of CHT1 internalization. K+ -depolarization also increases the size of the pool of CHT1 protein that can be mobilized to the plasma membrane. Thus, the activity-dependent increase in plasma membrane CHT1 localization appears to be regulated by two mechanisms: (i) an increase in the rate of externalization of the intracellular CHT1 pool; and (ii) the recruitment of additional intracellular transporters to the recycling pool. [source] Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in cultureEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Andrea Barberis Abstract The variability of quantal size depends on both presynaptic (profile of the neurotransmitter concentration in the cleft) and postsynaptic (number and gating properties of postsynaptic receptors) factors. Here we have examined the possibility that at nonsaturated synapses in cultured hippocampal neurons, changes in both the transmitter concentration peak and its clearance from the synaptic cleft may influence the variability of spontaneous miniature synaptic GABAergic currents (mIPSCs). We found that, in contrast to the slow-off GABAA receptor antagonist bicuculline, fast-off competitive antagonists such as SR-95103 and TPMPA differentially blocked small and large mIPSCs. In the presence of flurazepam, a drug believed to increase the affinity of GABA for GABAAR, small mIPSCs were enhanced more efficiently than large events. Moreover, the addition of dextran, which increases the viscosity of the extracellular fluid, preferentially increased small mIPSCs with respect to large ones. These observations suggest that changes in the concentration peak and the speed of GABA clearance in the cleft may be an important source of synaptic variability. The study of the correlation between peak amplitude and kinetics of mIPSCs allowed determination of the relative contribution of transmitter peak concentration vs. time of GABA clearance. Small synaptic responses were associated with fast onset and decay kinetics while large amplitude currents were asociated with slow kinetics, indicating a crucial role for GABA synaptic clearance in variability of mIPSCs. By using model simulations we were able to estimate the range of variability of both the concentration and the speed of clearance of the GABA transient in the synaptic cleft. [source] Synthesis and Structure of Macrolactams of 3,-Aminodeoxycholanic AcidEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2006Martin Feigel Abstract The macrolactams cyclo(3,-aminodeoxycholic amide)2 (1) and cyclo(3,-aminodeoxycholic amide)3 (2) were prepared in high yields (1: 32,%; 2: 41,%) from the pentafluorophenyl esters of the linear precursors. The solid-state structures of both macrocycles were determined by X-ray diffraction. Compound 1 forms a cleft of C2 symmetry which holds two methanol and two water molecules fixed by hydrogen bonds. The crystals of compound 2 contain two slightly different macrolactam rings of 7,8 Å diameter. The polar ,-surface of the deoxycholanic parts and the amide NH groups are oriented into the center of the rings. The cavity formed by the ring system and the void volume between the macrocycles is filled by disordered solvent molecules. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Specific cleavage of the DNase-I binding loop dramatically decreases the thermal stability of actinFEBS JOURNAL, Issue 18 2010Anastasia V. Pivovarova Differential scanning calorimetry was used to investigate the thermal unfolding of actin specifically cleaved within the DNaseI-binding loop between residues Met47-Gly48 or Gly42-Val43 by two bacterial proteases, subtilisin or ECP32/grimelysin (ECP), respectively. The results obtained show that both cleavages strongly decreased the thermal stability of monomeric actin with either ATP or ADP as a bound nucleotide. An even more pronounced difference in the thermal stability between the cleaved and intact actin was observed when both actins were polymerized into filaments. Similar to intact F-actin, both cleaved F-actins were significantly stabilized by phalloidin and aluminum fluoride; however, in all cases, the thermal stability of the cleaved F-actins was much lower than that of intact F-actin, and the stability of ECP-cleaved F-actin was lower than that of subtilisin-cleaved F-actin. These results confirm that the DNaseI-binding loop is involved in the stabilization of the actin structure, both in monomers and in the filament subunits, and suggest that the thermal stability of actin depends, at least partially, on the conformation of the nucleotide-binding cleft. Moreover, an additional destabilization of the unstable cleaved actin upon ATP/ADP replacement provides experimental evidence for the highly dynamic actin structure that cannot be simply open or closed, but rather should be considered as being able to adopt multiple conformations. Structured digital abstract ,,MINT-7980274: Actin (uniprotkb:P68135) and Actin (uniprotkb:P68135) bind (MI:0407) by biophysical (MI:0013) [source] The crystal structure of a xyloglucan-specific endo-,-1,4-glucanase from Geotrichum sp.FEBS JOURNAL, Issue 18 2009M128 xyloglucanase reveals a key amino acid residue for substrate specificity Geotrichum sp. M128 possesses two xyloglucan-specific glycoside hydrolases belonging to family 74, xyloglucan-specific endo-,-1,4-glucanase (XEG) and oligoxyloglucan reducing-end-specific cellobiohydrolase (OXG-RCBH). Despite their similar amino acid sequences (48% identity), their modes of action and substrate specificities are distinct. XEG catalyzes the hydrolysis of xyloglucan polysaccharides in endo mode, while OXG-RCBH acts on xyloglucan oligosaccharides at the reducing end in exo mode. Here, we determined the crystal structure of XEG at 2.5 Å resolution, and compared it to a previously determined structure of OXG-RCBH. For the most part, the amino acid residues that interact with substrate are conserved between the two enzymes. However, there are notable differences at subsite positions ,1 and +2. OXG-RCBH has a loop around the +2 site that blocks one end of the active site cleft, which accounts for its exo mode of action. In contrast, XEG lacks a corresponding loop at this site, thereby allowing binding to the middle of the main chain of the substrate. At the ,1 site in OXG-RCBH, Asn488 interacts with the xylose side chain of the substrate, whereas the ,1 site is occupied by Tyr457 in XEG. To confirm the contribution of this residue to substrate specificity, Tyr457 was substituted by Gly in XEG. The wild-type XEG cleaved the oligoxyloglucan at a specific site; the Y457G variant cleaved the same substrate, but at various sites. Together, the absence of a loop in the cleft and the presence of bulky Tyr457 determine the substrate specificity of XEG. [source] Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitroFEBS JOURNAL, Issue 17 2009Suzana Kovac Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin,gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin,ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8,10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo. Structured digital abstract ,,MINT-7212832, MINT-7212849: Apo-transferrin (uniprotkb:P02787) and Gamide (uniprotkb:P01350) bind (MI:0407) by surface plasmon resonance (MI:0107) ,,MINT-7212881, MINT-7212909: Ggly (uniprotkb:P01350) and Apo-transferrin (uniprotkb:P02787) bind (MI:0407) by cross-linking studies (MI:0030) ,,MINT-7212864: Apo-transferrin (uniprotkb:P02787) and Ggly (uniprotkb:P01350) bind (MI:0407) by competition binding (MI:0405) [source] Molecular determinants of ligand specificity in family 11 carbohydrate binding modules , an NMR, X-ray crystallography and computational chemistry approachFEBS JOURNAL, Issue 10 2008Aldino Viegas The direct conversion of plant cell wall polysaccharides into soluble sugars is one of the most important reactions on earth, and is performed by certain microorganisms such as Clostridium thermocellum (Ct). These organisms produce extracellular multi-subunit complexes (i.e. cellulosomes) comprising a consortium of enzymes, which contain noncatalytic carbohydrate-binding modules (CBM) that increase the activity of the catalytic module. In the present study, we describe a combined approach by X-ray crystallography, NMR and computational chemistry that aimed to gain further insight into the binding mode of different carbohydrates (cellobiose, cellotetraose and cellohexaose) to the binding pocket of the family 11 CBM. The crystal structure of C. thermocellum CBM11 has been resolved to 1.98 Å in the apo form. Since the structure with a bound substrate could not be obtained, computational studies with cellobiose, cellotetraose and cellohexaose were carried out to determine the molecular recognition of glucose polymers by CtCBM11. These studies revealed a specificity area at the CtCBM11 binding cleft, which is lined with several aspartate residues. In addition, a cluster of aromatic residues was found to be important for guiding and packing of the polysaccharide. The binding cleft of CtCBM11 interacts more strongly with the central glucose units of cellotetraose and cellohexaose, mainly through interactions with the sugar units at positions 2 and 6. This model of binding is supported by saturation transfer difference NMR experiments and linebroadening NMR studies. [source] Crystal structure of archaeal highly thermostable L -aspartate dehydrogenase/NAD/citrate ternary complexFEBS JOURNAL, Issue 16 2007Kazunari Yoneda The crystal structure of the highly thermostable l -aspartate dehydrogenase (l -aspDH; EC 1.4.1.21) from the hyperthermophilic archaeon Archaeoglobus fulgidus was determined in the presence of NAD and a substrate analog, citrate. The dimeric structure of A. fulgidusl -aspDH was refined at a resolution of 1.9 Å with a crystallographic R -factor of 21.7% (Rfree = 22.6%). The structure indicates that each subunit consists of two domains separated by a deep cleft containing an active site. Structural comparison of the A. fulgidusl -aspDH/NAD/citrate ternary complex and the Thermotoga maritimal -aspDH/NAD binary complex showed that A. fulgidusl -aspDH assumes a closed conformation and that a large movement of the two loops takes place during substrate binding. Like T. maritimal -aspDH, the A. fulgidus enzyme is highly thermostable. But whereas a large number of inter- and intrasubunit ion pairs are responsible for the stability of A. fulgidusl -aspDH, a large number of inter- and intrasubunit aromatic pairs stabilize the T. maritima enzyme. Thus stabilization of these two l -aspDHs appears to be achieved in different ways. This is the first detailed description of substrate and coenzyme binding to l -aspDH and of the molecular basis of the high thermostability of a hyperthermophilic l -aspDH. [source] Authentic interdomain communication in an RNA helicase reconstituted by expressed protein ligation of two helicase domainsFEBS JOURNAL, Issue 2 2007Anne R. Karow RNA helicases mediate structural rearrangements of RNA or RNA,protein complexes at the expense of ATP hydrolysis. Members of the DEAD box helicase family consist of two flexibly connected helicase domains. They share nine conserved sequence motifs that are involved in nucleotide binding and hydrolysis, RNA binding, and helicase activity. Most of these motifs line the cleft between the two helicase domains, and extensive communication between them is required for RNA unwinding. The two helicase domains of the Bacillus subtilis RNA helicase YxiN were produced separately as intein fusions, and a functional RNA helicase was generated by expressed protein ligation. The ligated helicase binds adenine nucleotides with very similar affinities to the wild-type protein. Importantly, its intrinsically low ATPase activity is stimulated by RNA, and the Michaelis,Menten parameters are similar to those of the wild-type. Finally, ligated YxiN unwinds a minimal RNA substrate to an extent comparable to that of the wild-type helicase, confirming authentic interdomain communication. [source] Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B12 biosynthesis, and CbiL in complex with S -adenosylhomocysteine , implications for the reaction mechanismFEBS JOURNAL, Issue 2 2007Kei Wada During anaerobic cobalamin (vitamin B12) biosynthesis, CbiL catalyzes methylation at the C-20 position of a cyclic tetrapyrrole ring using S -adenosylmethionine as a methyl group source. This methylation is a key modification for the ring contraction process, by which a porphyrin-type tetrapyrrole ring is converted to a corrin ring through elimination of the modified C-20 and direct bonding of C-1 to C-19. We have determined the crystal structures of Chlorobium tepidum CbiL and CbiL in complex with S -adenosylhomocysteine (the S -demethyl form of S -adenosylmethionine). CbiL forms a dimer in the crystal, and each subunit consists of N-terminal and C-terminal domains. S -Adenosylhomocysteine binds to a cleft between the two domains, where it is specifically recognized by extensive hydrogen bonding and van der Waals interactions. The orientation of the cobalt-factor II substrate was modeled by simulation, and the predicted model suggests that the hydroxy group of Tyr226 is located in close proximity to the C-20 atom as well as the C-1 and C-19 atoms of the tetrapyrrole ring. These configurations allow us to propose a catalytic mechanism: the conserved Tyr226 residue in CbiL catalyzes the direct transfer of a methyl group from S -adenosylmethionine to the substrate through an SN2-like mechanism. Furthermore, the structural model of CbiL binding to its substrate suggests the axial residue coordinated to the central cobalt of cobalt-factor II. [source] Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albuminFEBS JOURNAL, Issue 24 2005Alessio Bocedi Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional capacity to bind ligands (e.g. heme and drugs). Here, binding of the anti-HIV drugs abacavir, atazanavir, didanosine, efavirenz, emtricitabine, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, and zidovudine to HSA and ferric heme,HSA is reported. Ferric heme binding to HSA in the absence and presence of anti-HIV drugs was also investigated. The association equilibrium constant and second-order rate constant for the binding of anti-HIV drugs to Sudlow's site I of ferric heme,HSA are lower by one order of magnitude than those for the binding of anti-HIV drugs to HSA. Accordingly, the association equilibrium constant and the second-order rate constant for heme binding to HSA are decreased by one order of magnitude in the presence of anti-HIV drugs. In contrast, the first-order rate constant for ligand dissociation from HSA is insensitive to anti-HIV drugs and ferric heme. These findings represent clear-cut evidence for the allosteric inhibition of anti-HIV drug binding to HSA by the heme. In turn, anti-HIV drugs allosterically impair heme binding to HSA. Therefore, Sudlow's site I and the heme cleft must be functionally linked. [source] Mutation of residues in the coenzyme binding pocket of Dopa decarboxylaseFEBS JOURNAL, Issue 10 2001Effects on catalytic properties Residues D271, H192, H302 and N300 of l -3,4-dihydroxyphenylalanine decarboxylase (DDC), a homodimeric pyridoxal 5,-phosphate (PLP) enzyme, were mutated in order to acquire information on the catalytic mechanism. These residues are potential participants in catalysis because they belong to the common PLP-binding structural motif of group I, II and III decarboxylases and other PLP enzymes, and because they are among the putative active-site residues of structural modelled rat liver DDC. The spectroscopic features of the D271E, H192Q, H302Q and N300A mutants as well as their dissociation constants for PLP suggest that substitution of each of these residues causes alteration of the state of the bound coenzyme molecule and of the conformation of aromatic amino acids, possibly in the vicinity of the active site. This supports, but does not prove, the possibility that these residues are located in the coenzyme-binding cleft. Interestingly, mutation of each residue generates an oxidative decarboxylase activity towards l -3,4-dihydroxyphenylalanine (l -Dopa), not inherent in the wild-type in aerobiosis, and reduces the nonoxidative decarboxylase activity of l -Dopa from 3- to 390-fold. The partition ratio between oxidative and nonoxidative decarboxylation ranges from 5.7 × 10,4 for N300A mutant to 946 × 10,4 for H302Q mutant. Unlike wild-type enzyme, the mutants catalyse these two reactions to the same extent either in the presence or absence of O2. In addition, all four mutants exhibit an extremely low level of the oxidative deaminase activity towards serotonin with respect to wild-type. All these findings demonstrate that although D271, H192, H302 and N300 are not essential for catalysis, mutation of these residues alters the nature of catalysis. A possible relationship among the integrity of the PLP cleft, the productive binding of O2 and the transition to a closed conformational state of DDC is discussed. [source] Sympathetic control of short-term heart rate variability and its pharmacological modulationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007Jean-Luc Elghozi Abstract The static relationship between heart rate (HR) and the activity of either vagal or sympathetic nerves is roughly linear within the physiological range of HR variations. The dynamic control of HR by autonomic nerves is characterized by a fixed time delay between the onset of changes in nerve activity and the onset of changes in HR. This delay is much longer for sympathetically than for vagally mediated changes in HR. In addition, the kinetics of the HR responses shows the properties of a low-pass filter with short (vagal) and long (sympathetic) time constants. These differences might be secondary to differences in nervous conduction times, width of synaptic cleft, kinetics of receptor activation and post-receptor events. Because of the accentuated low-pass filter characteristics of the HR response to sympathetic modulation, sympathetic influences are almost restricted to the very-low-frequency component of HR variability, but the chronotropic effects of vagal stimulation usually predominate over those of sympathetic stimulation in this frequency band. Oscillations in cardiac sympathetic nerve activity are not involved in respiratory sinus arrhythmia (high-frequency component) and make a minor contribution to HR oscillations of approximately 10-s period (low-frequency component of approximately 0.1 Hz), at least in the supine position. In the latter case, HR oscillations are derived mainly from a baroreflex, vagally mediated response to blood pressure Mayer waves. Beta-blockers and centrally acting sympathoinhibitory drugs share the ability to improve the baroreflex control of HR, possibly through vagal facilitation, which might be beneficial in several cardiovascular diseases. [source] Diamond Transistor Array for Extracellular Recording From Electrogenic CellsADVANCED FUNCTIONAL MATERIALS, Issue 18 2009Markus Dankerl Abstract The transduction of electric signals from cells to electronic devices is mandatory for medical applications such as neuroprostheses and fundamental research on communication in neuronal networks. Here, the use of diamond with its advantages for biological applications as a new material for biohybrid devices for the detection of cell signals is investigated. Using the surface conductivity of hydrogen-terminated single-crystalline diamond substrates, arrays of solution-gate field-effect transistors were fabricated. The characterization of the transistors reveals a good stability in electrolyte solutions for at least 7 days. On these devices, cardiomyocyte-like HL-1 cells as well as human embryonic kidney cells (HEK293), which were stably transfected with potassium channels, are cultured. Both types of cells show healthy growth and good adhesion to the substrate. The diamond transistors are used to detect electrical signals from both types of cells by recording the extracellular potential. For the HL-1 cells, the shape of action potentials can be resolved and the propagation of the signal across the cell layer is visible. Potassium currents of HEK293 cells are activated with the patch-clamp technique in voltage-clamp mode and simultaneously measured with the field-effect transistors. The ion sensitivity of the diamond surface enables the detection of released potassium ions accumulated in the cleft between transistor and cell. [source] Sporadic dystrophic epidermolysis bullosa with albopapuloid and prurigo- and folliculitis-like lesionsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2009Yi-Ming Fan MD A case of sporadic dystrophic epidermolysis bullosa (DEB) with albopapuloid and prurigo- and folliculitis-like lesions is reported. Histopathology of the scalp biopsy showed hyperkeratosis, a subepidermal cleft near the orifice of a hair follicle, dermal fibrosis, and a moderate perivascular and perifollicular lymphohistiocytic inflammatory cell infiltrate in the papillary dermis, without neutrophilic infiltrate in the orifice of the hair follicle. It is uncertain whether the present case should be classified as DEB pruriginosa or represents a new subtype of DEB. [source] An unusual association of pemphigus vulgaris with hyperprolactinemiaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2002MNAMS, Sujay Khandpur MD A 21-year-old unmarried woman presented with oral ulcerations and generalized, itchy, fluid-filled, skin lesions of 10 days' duration. The lesions ruptured spontaneously, resulting in extensive denuded areas covered by crusts. One month prior to this, she experienced pain and enlargement of both breasts with galactorrhea. Her menstrual cycles were normal initially, but later she developed menstrual irregularities. No past history suggestive of any other systemic or skin disease, including atopy or drug allergies, could be obtained. Her family history was not contributory. Dermatologic examination revealed multiple, flaccid bullae and extensive denuded areas of skin covered with crusts over the scalp, face, trunk, and upper and lower limbs (Fig. 1). Bulla spread sign and Nikolsky's sign were positive. The oral mucosa, including the lips, buccal surface, tongue, and palate, showed multiple erosions covered with necrotic slough. The rest of the mucocutaneous and systemic examination was within normal limits. Figure 1. Extensive erosions and flaccid bullae over the trunk with breast enlargement The patient's diagnostic work-up revealed: hemoglobin, 11.2 g%; total leukocyte count, 7400/mm3; differential leukocyte count, P62L34E2M2; erythrocyte sedimentation rate, 34 mm/h. A peripheral blood smear examination, urinalysis, blood sugar, and renal and liver function tests were normal. Venereal Disease Research Laboratory (VDRL) test and enzyme-linked immunoabsorbent assay (ELISA) for human immunodeficiency virus (HIV) were nonreactive. Antinuclear antibody, lupus erythematosus (LE) cell, rheumatoid factor, and anti-dsDNA levels were normal. Serum protein electrophoresis demonstrated increased levels of immunoglobulin G (IgG) antibody. The serum prolactin level was significantly raised to 139.49 ng/mL (normal, 3.6,18.9 ng/mL). The sex hormone levels, however, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone, were within normal limits. The thyroid hormone profile was also unaltered. Chest X-ray was normal. Ultrasound of the abdomen and pelvis revealed no visceral abnormality and computerized tomography (CT) scan of the pituitary sella showed no adenoma. Mammography was negative for breast malignancy. A Tzanck smear prepared from the base of the erosion showed multiple acantholytic cells and lymphocytes. Histologic examination from an intact vesicle was suggestive of pemphigus vulgaris (PV), showing a suprabasal cleft with acantholytic cells and the basal layer demonstrating a "row of tombstones" appearance (Fig. 2). Direct immunofluorescence (DIF) revealed the intercellular deposition of IgG and C3 throughout the epidermis in a "fishnet pattern." Indirect immunofluorescence (IIF) test performed on rat esophagus for circulating IgG antibody was positive in a titer of 1 : 120. Figure 2. Photomicrograph showing suprabasal cleft with "row of tombstones" appearance, suggestive of pemphigus vulgaris (hematoxylin and eosin, × 40) Based on the clinical and immunohistological features, a diagnosis of PV with idiopathic hyperprolactinemia was made. The patient was treated with bromocriptine mesylate (Tablet Proctinal, Glaxo Wellcome Ltd, India) at a dose of 2.5 mg twice a day. After 2 months of therapy, significant improvement in the skin lesions was observed. The existing lesions re-epithelialized with a drastic reduction in the number and distribution of new vesicles. However, no change in the mucosal erosions was noticed. IIF test demonstrated a lower antibody titer (1 : 40). The breast complaints also improved with a reduction in serum prolactin level to 6.5 ng/mL. The patient refused further treatment as she experienced nausea and dizziness with bromocriptine. After 2 weeks, the disease relapsed with the appearance of new vesicles over the forearms, abdomen, back, and thighs. She again complained of breast tenderness and galactorrhea, and the serum prolactin level was 95 ng/mL. The IgG titer increased to 1 : 120. Hence, treatment with oral prednisolone (2 mg/kg/day) and bromocriptine (2.5 mg twice a day) with an antiemetic was initiated. After 6 weeks, the skin lesions had cleared completely, the breast symptoms had improved, menses had become regular, and the prolactin level had decreased to 4 ng/mL. IIF test was negative for circulating antibody. Steroids were tapered off and maintenance therapy with bromocriptine at a dose of 2.5 mg/day was continued. [source] A medieval example of a sagittal cleft or ,butterfly' vertebraINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 6 2003T. Anderson Abstract A mature adult medieval male with a rare congenital anomaly, a sagittal-cleft or butterfly vertebra, is presented. Clinical cases are frequently associated with axial as well as soft-tissue defects. The present case, based only on skeletal evidence, appears to be an isolated finding. The aetiology of the clefting is outlined and palaeopathological evidence for the condition is included. Copyright © 2003 John Wiley & Sons, Ltd. [source] Usefulness of Intraoperative Real-Time 3D Transesophageal Echocardiography in Cardiac SurgeryJOURNAL OF CARDIAC SURGERY, Issue 6 2008Thierry V. Scohy M.D. Methods: Preoperative transthoral echocardiography (TTE) revealed: hypertrophic ventricular septum (TTE:19.3 mm), systolic anterior motion (SAM) not causing obstruction and malcoaptation of the anterior mitral valve leaflet (AMVL), and posterior mitral valve leaflet (PMVL) with severe mitral regurgitation. Results: Intraoperative TEE with a x7-2t MATRIX-array transducer (Philips, Andover, MA, USA) with a transducer frequency of x7,2 t mHz, connected to a iE33 (Philips), shows us that the main mechanism and site of regurgitation was an AMVL cleft. We also measured a 24.3-mm thickness of the ventricular septum and analyzing the 3D full volume acquisition revealed that there was no SAM. Conclusion: Intraoperative RT3DTEE permitted comprehensive 3D viewing of the mitral valve revealing the mechanism of mitral valve regurgitation, SAM, and the exact width of the hypertrophic ventricular septum. [source] Intracellular dynamics of Smad-mediated TGF, signalingJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2003Robert M. Greene The transforming growth factor-, (TGF,) family represents a class of signaling molecules that plays a central role in morphogenesis, growth, and cell differentiation during normal embryonic development. Members of this growth factor family are particularly vital to development of the mammalian secondary palate where they regulate palate mesenchymal cell proliferation and extracellular matrix synthesis. Such regulation is particularly critical since perturbation of either cellular process results in a cleft of the palate. While the cellular and phenotypic effects of TGF, on embryonic craniofacial tissue have been extensively catalogued, the specific genes that function as downstream mediators of TGF, action in the embryo during palatal ontogenesis are poorly defined. Embryonic palatal tissue in vivo and murine embryonic palate mesenchymal (MEPM) cells in vitro secrete and respond to TGF,. In the current study, elements of the Smad component of the TGF, intracellular signaling system were identified and characterized in cells of the embryonic palate and functional activation of the Smad pathway by TGF,1, TGF,2, and TGF,3 was demonstrated. TGF,-initiated Smad signaling in cells of the embryonic palate was found to result in: (1) phosphorylation of Smad 2; (2) nuclear translocation of the Smads 2, 3, and 4 protein complex; (3) binding of Smads 3 and 4 to a consensus Smad binding element (SBE) oligonucleotide; (4) transactivation of transfected reporter constructs, containing TGF,-inducible Smad response elements; and (4) increased expression of gelatinases A and B (endogenous genes containing Smad response elements) whose expression is critical to matrix remodeling during palatal ontogenesis. Collectively, these data point to the presence of a functional Smad-mediated TGF, signaling system in cells of the developing murine palate. J. Cell. Physiol. 197: 261,271, 2003. © 2003 Wiley-Liss, Inc. [source] Periodontal attachment loss over 14 years in cleft lip, alveolus and palate (CLAP, CL, CP) subjects not enrolled in a supportive periodontal therapy programJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2003Giovanni E. Salvi Abstract Objectives: (i) To assess the overall and (ii) cleft-associated rate of periodontal disease (PD) progression in subjects with cleft lip, alveolus and palate (CLAP) and (iii) to compare these rates with those of subjects with cleft lip (CL) and cleft palate (CP). Material and methods: Twenty-six subjects not enrolled in a supportive periodontal therapy (SPT) program were examined in 1979, 1987 and 1993. PD progression was assessed as increase in pocket probing depth (PPD in mm) and probing attachment loss (PAL in mm). Results: Extensive plaque accumulation and high frequencies of gingival units bleeding on probing were observed at all three examinations. A statistically significant increase in mean PPD of 0.57±0.21 mm (SD) in both groups as well as a statistically significant loss of PAL of 1.85±0.23 mm (SD) in the CLAP group and of 1.72±0.21 mm (SD) in the CL/CP group occurred over the observation period (p<0.05). In subjects with CLAP, statistically significant increases in PPD and loss of PAL were recorded over time at sites adjacent to the cleft as well as at control sites (p<0.05). Over 14 years, however, PPD increased 1.72±1.08 mm (SD) at cleft sites versus 0.72±1.14 mm (SD) at control sites (p<0.05), and PAL amounted to 3.19±1.35 mm (SD) at cleft sites versus 2.41±1.52 mm (SD) at control sites (p<0.05). Conclusion: Both the CLAP and the CL/CP subjects are at high risk for PD progression if no SPT program is provided. This also suggests that alveolar cleft sites in subjects with high plaque and gingival inflammation scores underwent more periodontal tissue destruction than control sites over a 14-year period. Zusammenfassung Ziele: 1. Beurteilung der gesamten und 2. der mit der Spalte assoziierten Progressionsrate der Parodontalerkrankung (PD) bei Patienten mit Lippen-Kiefer-Gaumenspalten (CLAP) und 3. der Vergleich dieser Progressionsraten mit denen von Patienten mit Lippenspalten (CL) sowie Gaumenspalten (CP). Material und Methoden: 26 Patienten, die nicht an einem SPT-Programm teilnahmen wurden in 1979, 1987 und 1993 untersucht. Die PD-Progression wurde über die Zunahme der Sondierungstiefe (PPD in mm) und den klinischen Attachmentverlust (PAL in mm) beurteilt. Ergebnisse: Bei allen drei Untersuchungszeitpunkten wurde eine ausgedehnte Plaqueakkumulation und eine große Häufigkeit von Gingivabereichen, die bei Sondierung bluteten beobachtet. Während der Beobachtungsperiode fand in beiden Gruppen ein statistisch signifikanter Anstieg der mittleren PPD von 0.57±0.21 mm (SD) als auch ein statistisch signifikanter Attachmentverlust von 1.85±0.23 mm (SD) in der CLAP-Gruppe sowie von 1.72±0.21 mm (SD) in der CL/CP-Gruppe statt (p<0.05). Bei den Patienten mit CLAP wurde im Laufe der Zeit sowohl an den Parodontien neben der Spalte als auch an den Kontrollstellen (p<0.05) ein statistisch signifikanter Anstieg der PPD und Attachmentverlust registriert. Während der 14 Jahre jedoch nahm die PPD an Stellen mit Spalte um 1.72±1.08 mm (SD) zu im Gegensatz zu den Kontrollstellen (p<0.05) wo dieser Wert 0.72±1.14 mm (SD) betrug. Für den Attachmentverlust lag dieser Wert bei 3.19±1.35 mm (SD) an den Stellen mit Spalte im Gegensatz zu den Kontrollstellen (p<0.05) mit 2.41±1.52 mm (SD). Schlussfolgerung: Wenn keine parodontale Erhaltungstherapie zur Verfügung gestellt wird haben beide Personen, die mit CLAP und die mit CL/CP ein hohes Risiko hinsichtlich der Parodontitisprogression. Dies läßt annehmen, dass bei Personen mit viel Plaque und ausgeprägter Entzündung der Gingiva, die Stellen mit Kieferspalten während einer 14-jährigen Zeitperiode eine stärkere Zerstörung der parodontalen Gewebe erfahren als die Kontrollstellen. Résumé Les buts de cette étude ont été de suivre la progression du taux de la maladie parodontale associée au bec de lièvre (CLAP) et de comparer ces taux avec ceux de sujets ayant lèvre fendue (CL) et palais fendu (CP). Vingt-six sujets non-soumis à un programme parodontal de maintien (SPT) ont été examinés en 1979, 1987 et 1993. La progression PD a été enregistrée telle une augmentation de la profondeur au sondage (PPD en mm) et une perte d'attache au sondage (PAL en mm). Une énorme accumulation de plaque dentaire et de très hautes fréquences dans les nombres d'unités gingivales avec saignement au sondage ont été observées lors des trois examens. Une augmentation statistiquement significative dans la moyenne PPD de 0.57±0.21 mm (SD) dans les deux groupes ainsi qu'une perte significative de PAL de 1.85±0.23 mm (SD) dans le groupe CLAP et de 1.72±0.21 mm (SD) dans le groupe CL/CP apparaîssaient durant cette période d'observation (p<0.05). Chez les sujets avec CLAP, les augmentations statistiquement significatives de PPD et la perte de PAL ont été enregistrées avec le temps sur les sites adjacents au bec de lièvre ainsi qu'au niveau des sites contrôles (p<0.05). Sur les quatorze années, cependant, PPD augmentait de 1.72±1.08 mm (SD) au niveau des sites bec de lièvre vs 0.72±1.14 mm (SD) au niveau des contrôles (p<0.05), et PAL s'élevait à 3.19±1.35 mm (SD) au niveau des sites bec de lièvre vs 2.41±1.52 mm au niveau des contrôles (p<0.05). Tant les sujets CLAP que les CL/CP étaient à haut risque pour la progression PD si un programme SPT n'était pas suivi. Ceci suggère également que les sites alvéolaires associés au bec de lièvre avec des scores de plaque et de gingivite importants s'accompagnaient de plus de destruction que les sites contrôles sur une période de quatorze années. [source] How does acantholysis occur in pemphigus vulgaris: a critical reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2006Alessandro Lanza Background:, Pemphigus vulgaris is a life-threatening autoimmune blistering disease targeting skin and mucous membranes, characterized by disruption of keratinocytes' adhesion termed acantholysis. Today multiple classes of targets are considered to play a role in the genesis of the acantholysis; of these, the classical pemphigus antigens, desmosomal cadherins (desmoglein 1 and 3) are the best characterized and considered as the most important. Additional antigens include the novel epithelial acetylcholine receptors (,9 and pemphaxin). Thus, acantholysis in pemphigus seems to result from a cooperative action of antibodies to different keratinocyte self-antigens, but the mechanisms by which epithelial cleft occurs are not yet clearly understood. In fact, the binding of the autoantibodies to these targets generates a plethora of biological effects due, on one hand, to their direct interference with adhesive function and, on the other, to more complex events involving intracellular pathways that modify proteases activity or calcium metabolism, leading to loss of cell,cell adhesion. [source] DNA aptamers developed against a soman derivative cross-react with the methylphosphonic acid core but not with flanking hydrophobic groupsJOURNAL OF MOLECULAR RECOGNITION, Issue 3 2009John G. Bruno Abstract Twelve rounds of systematic evolution of ligands by exponential enrichment (SELEX) were conducted against a magnetic bead conjugate of the para -aminophenylpinacolylmethylphosphonate (PAPMP) derivative of the organophosphorus (OP) nerve agent soman (GD). The goal was to develop DNA aptamers that could scavenge GD in vivo, thereby reducing or eliminating the toxic effects of this dangerous compound. Aptamers were sequenced and screened in peroxidase-based colorimetric plate assays after rounds 8 and 12 of SELEX. The aptamer candidate sequences exhibiting the highest affinity for the GD derivative from round 8 also reappeared in several clones from round 12. Each of the highest affinity PAPMP-binding aptamers also bound methylphosphonic acid (MPA). In addition, the aptamer with the highest overall affinity for PAPMP carried a sequence motif (TTTAGT) thought to bind MPA based on previously published data (J. Fluoresc 18: 867,876, 2008). This sequence motif was found in several other relatively high affinity PAPMP aptamer candidates as well. In studies with the nerve agent GD, pre-incubation of a large molar excess of aptamer candidates failed to protect human butyrylcholinesterase (BuChE) from inhibition. With the aid of three-dimensional molecular modeling of the GD derivative it appears that a hydrophilic cleft sandwiched between the pinacolyl group and the p -aminophenyl ring might channel nucleotide interactions to the phosphonate portion of the immobilized GD derivative. However, bona fide GD free in solution may be repulsed by the negative phosphate backbone of aptamers and rotate its phosphonate and fluorine moieties away from the aptamer to avoid being bound. Future attempts to develop aptamers to GD might benefit from immobilizing the pinacolyl group of bona fide GD to enhance exposure of the phosphonate and fluorine to the random DNA library. Copyright © 2008 John Wiley & Sons, Ltd. [source] Applications of time-resolved resonance energy transfer measurements in studies of the molecular crowding effect,JOURNAL OF MOLECULAR RECOGNITION, Issue 5 2004Varda Ittah Abstract The native structures of many globular proteins are only weakly stabilized and form in solution ensembles of multiple conformers. The energy differences between the conformers are assumed to be small. This is the case of flexible multidomain proteins where domain motions were observed. High concentrations of inert macrosolute, which create a crowded or confined environment, can cause shifts of the distribution of the conformers of such proteins towards the more compact structures. This effect may also promote compact structures in partially folded proteins. Time-resolved dynamic non-radiative excitation energy transfer (tr-RET) is suitable for detection of either subtle or major changes in distributions of intramolecular distances in protein molecules in solutions. Two experiments were performed which demonstrated the applicability of tr-RET for detection of the effect of macrosolutes on the conformational ensembles of flexible states of protein molecules. The distribution of distances between residues 203 and 169 in the CORE domain of E. coli adenylate kinase (AK) in the denatured state was determined in the presence of high concentrations of dextran 40. A significant shift of the mean of the distribution was observed without reduction of its width. This was interpreted as a shift to compact structure without change of the degree of disorder of the chain. In a second experiment the distribution of the distance between residues 55 and 169 in AK, which spans the cleft between the CORE and the AMPbind domains, was monitored. No clear effect of high concentrations of dextran 40 was found. These experiments show the strength of the application of tr-RET in investigation of changes in the sub-states of flexible conformations of globular protein. Networks of pairs of labeled sites can be prepared and tr-RET experiments can be performed in order to search for the segments of the protein molecules, which respond to the presence of inert macromolecules in their environment. Copyright © 2004 John Wiley & Sons, Ltd. [source] Ultrastructure of the protonephridial system in Neodasys chaetonotoideus (Gastrotricha: Chaetonotida) and in the ground pattern of Gastrotricha,JOURNAL OF MORPHOLOGY, Issue 7 2007Alexander Kieneke Abstract The taxon Neodasys has a basal position within Gastrotricha. This makes it very interesting for phylogenetic considerations in this group. To complete the reconstruction of the nephridial system in the stem species of Gastrotricha started earlier, we have studied the whole protonephridial system of Neodasys chaetonotoideus by means of complete sets of ultrathin sections and TEM. In many characters, protonephridia of N. chaetonotoideus resemble those of macrodasyidan gastrotrich species. For example, each of the six protonephridia, arranged in three pairs, consists of three distinct cells that constitute the continuous protonephridial lumen. Especially, the terminal cell of the protonephridia of N. chaetonotoideus shows a striking pattern: The perforation of the filter region is a meandering cleft that is continuous with the seam of the enfolded lumen of that cell. With the results presented here and that of former TEM studies, we give a comprehensive idea of the excretory organs in the ground pattern of Gastrotricha. Moreover, we can elaborate on the hypothesized protonephridial system in the stem species of Bilateria. We suggest that a meandering filtration cleft is a feature of the ground pattern of the Bilateria. J. Morphol., 2007. © 2007 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||