Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Axial patterning of the aboral end of the hydra body column was examined using expression data from two genes. One, shin guard, is a novel receptor protein-tyrosine kinase gene expressed in the ectoderm of the peduncle, the end of the body column adjacent to the basal disk. The other gene, manacle, is a paired-like homeobox gene expressed in differentiating basal disk ectoderm. During regeneration of the aboral end, expression of manacle precedes that of shin guard. This result is consistent with a requirement for induction of peduncle tissue by basal disk tissue. Our data contrast with data on regeneration of the oral end. During oral end regeneration, markers for tissue of the tentacles, which lie below the extreme oral end (the hypostome), are detected first. Later, markers for the hypostome itself appear at the regenerating tip, with tentacle markers displaced to the region below. Additional evidence that tissue can form basal disk without passing through a stage as peduncle tissue comes from LiCl-induced formation of patches of ectopic basal disk tissue. While manacle is ectopically expressed during formation of basal disk patches, shin guard is not. The genes examined also provide new information on development of the aboral end in buds. Although adult hydra are radially symmetrical, expression of both genes in the bud's aboral end is initially asymmetrical, appearing first on the side of the bud closest to the parent's basal disk. The asymmetry can be explained by differences in positional information in the body column tissue that evaginates to form a bud. As predicted by this hypothesis, grafts reversing the orientation of evaginating body column tissue also reverse the orientation of asymmetrical gene expression.
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PMID:Expression of a novel receptor tyrosine kinase gene and a paired-like homeobox gene provides evidence of differences in patterning at the oral and aboral ends of hydra. 1075 14

The formation of vasoconstrictors (e.g., angiotensin II and endothelin) and the inactivation of vasodilators (e.g., bradykinin and atrial natriuretic) by membrane-bound zinc metallopeptidases are key mechanisms in the control of blood pressure and fluid homeostasis. The way in which these peptides modulate physiological functions has been intensively studied. With the aim to develop compounds that can jointly block the three metallopeptidases-neutral endopeptidase (NEP, neprilysin), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE-1)-we studied the common structural specificity of the S1' subsites of these peptidases. Various mercaptoacyl amino acids of the general formula HS-CH2-CH(R1')CO-Trp-OH, possessing more or less constrained R1' side chains, were designed. The mercapto-acyl synthons contain one or two asymmetrical centers. The K(i) values of the separated stereoisomers of the most efficient inhibitors were used to determine the stereochemical preference of each enzyme. A guideline for the joint inhibition of the three peptidases was obtained with the (2R,3R) isomer of compound 13b. Its K(i) values on NEP, ACE, and ECE were 0.7, 43, and 26 nM, respectively.
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PMID:Toward an optimal joint recognition of the S1' subsites of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE), and neutral endopeptidase (NEP). 1190 89

The expression of phosphorylated extracellular signal-regulated kinase 1/2 (pERK 1/2) was evaluated in the vestibular nuclei (VN) of rats following unilateral labyrinthectomy (UL). Immunohistochemistry revealed a significant asymmetrical increase in pERK 1/2 expression in the VN, 5 min after UL, after which pERK 1/2 immunoreactivity decreased rapidly and was undetectable by 90 min after UL. These results suggest that unilateral deafferentation of the vestibular system triggers intracellular signal pathways that activate ERK 1/2 in the VN.
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PMID:Asymmetric activation of extracellular signal-regulated kinase 1/2 in rat vestibular nuclei by unilateral labyrinthectomy. 1515 10

Mutations in genes known to be responsible for most of the recognizable syndromes associated with bilateral coronal synostosis can be detected by molecular testing. The genetic alterations that could cause unilateral coronal synostosis are more elusive. It is recognized that FGFR and TWIST mutations can give rise to either bilateral or unilateral coronal synostosis, even in the same family. The authors undertook a prospective study of patients presenting with synostotic frontal plagiocephaly (unilateral coronal synostosis) to Children's Hospital Boston during the period from 1997 to 2000. Mutational analysis was performed on all patients and on selected parents whenever familial transmission was suspected. Intraoperative anthropometry was used in an effort to differentiate those patients in whom a mutation was detected from those in whom it was not. The anthropometric measures included bilateral sagittal orbital-globe distance, inter medial canthal distance, and nasal angulation. Macrocephaly and palpebral angulation were also considered possible determinants. There was a 2:1 female preponderance in 47 patients with synostotic frontal plagiocephaly. Mutations were found in eight of 47 patients: two patients with different single-amino-acid changes in FGFR2, three patients with FGFR3 Pro250Arg, and three patients with TWIST mutations. Another patient had craniofrontonasal syndrome for which a causative locus has been mapped to chromosome X, although molecular testing is not yet available. Two features were strongly associated with a detectable mutation in patients with synostotic frontal plagiocephaly: asymmetrical brachycephaly (retrusion of both supraorbital rims) and orbital hypertelorism. Other abnormalities in the craniofacial region and extremities were clues to a particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. Neither macrocephaly nor degree of nasal angulation nor relative vertical position of the lateral canthi correlated with mutational detection. An additional four patients in this study had either unilateral or bilateral coronal synostosis in an immediate relative and had anthropometric findings that predicted a mutation, and yet no genetic alteration was found. This suggests either that the authors' screening methods were not sufficiently sensitive or that perhaps there are other unknown pathogenic loci. Nevertheless, molecular testing is recommended for infants who have unilateral coronal synostosis, particularly if there are the anthropometric findings highlighted in this study or an otherwise suspicious feature in the child or a parent. Infants with either an identified or a suspected mutation usually need bilateral asymmetric advancement of the bandeau and may be more likely to require frontal revision in childhood.
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PMID:Molecular analysis of patients with synostotic frontal plagiocephaly (unilateral coronal synostosis). 1525 76

WNT/planar cell polarity (PCP) signaling pathway controls tissue polarity and cell movement through the activation of RHOA, c-Jun N-terminal kinase (JNK), and nemo-like kinase (NLK) signaling cascades. PCP is induced in Drosophila by the asymmetrical localization of Frizzled-Dishevelled-Diego-Starry night (Flamingo) complex and Van Gogh (Strabismus)-Prickle complex. Here, WNT/PCP signaling pathway implicated in human carcinogenesis is reviewed. Human WNT5A, WNT5B, and WNT11 are representative non-canonical WNTs transducing PCP signals through FZD3 or FZD6 receptors, and ROR1, ROR2 or PTK7 co-receptors. Human VANGL1, VANGL2 (Van Gogh homologs), CELSR1, CELSR2, CELSR3 (Starry night homologs), DVL1, DVL2, DVL3 (Dishevelled homologs), PRICKLE1, PRICKLE2 (Prickle homologs), and ANKRD6 (Diego homolog) are core PCP signaling molecules. MAGI3 assembles FZD, VANGL, PTEN, and adhesion molecules. Dishevelled-dependent WNT/PCP signals are transduced to the RHOA signaling cascade through Formin homology proteins DAAM1 and DAAM2, and to the JNK signaling cascade through MAPKKKs and MAPKK4/7. Dishevelled-independent WNT/ PCP signals are transduced to the NLK signaling cascade through MAP3K7 (TAK1). ANKRD6, NKD1 and NKD2 induce class switch from the WNT/GSK3beta signaling pathway to the WNT/PCP signaling pathway. WNT5A is up-regulated in various types of human cancer, such as gastric cancer, lung cancer, and melanoma. FZD3/FZD6 receptor and ROR2 co-receptor transduce WNT5A signal in gastric cancer. Aberrant activation of WNT/PCP signaling pathway in human cancer leads to more malignant phenotypes, such as abnormal tissue polarity, invasion, and metastasis. cDNA-PCR, microarray or ELISA reflecting aberrant activation of WNT/PCP signaling pathway could be developed as novel cancer prognostics. Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) of WNT/PCP signaling molecules mentioned above are suitable for use in screening of cancer predisposition, especially for gastric cancer. Antibody, RNAi, or small molecule compounds to regulate the function of WNT/PCP signaling molecules mentioned above are good candidates for development as novel cancer therapeutics.
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PMID:WNT/PCP signaling pathway and human cancer (review). 1627 60

Developmental processes mediating the initiation of lineage commitment from self-renewing neural stem cells (NSCs) remain mostly unclear because of the persisting ambiguity in identifying true NSCs from proliferative lineage-restricted progenitors (LRPs), which are directly or indirectly derived from NSCs. Our multilineage immunohistochemical analyses of early embryonic rat telencephalon at the onset of neurogenesis revealed clear dorsoventral gradients in the emergence of two types of neuronal progenitors (NPs) from multilineage-negative NSCs. Enumeration of NSCs using comprehensive flow cytometric analysis demonstrated that their precipitous decline in vivo involved both active differentiation into NPs and an increased propensity toward apoptosis. Both processes paralleled the dorsoventral changes in fibroblast growth factor receptor (FGFR) expressions. NSCs residing in the dorsal telencephalon coexpressed FGFR1 and FGFR3, whereas those residing in the ventral telencephalon also expressed FGFR2. NSCs exposed to basic fibroblast growth factor (bFGF) in vitro generated four stereotypical clonal expansion states: efficiently self-renewing, inefficiently self-renewing limited by apoptosis, exclusively neurogenic, and multipotential, generating up to five types of LRPs. The plasticity among these expansion states depended on ambient [bFGF], telencephalic developmental stage, and differential activation/inactivation of specific FGFRs. Coactivation of FGFR1 and FGFR3 promoted symmetrical divisions of NSCs (self-renewal), whereas inactivation of either triggered asymmetrical divisions and neurogenesis from these cells. Developmental upregulation of FGFR2 expression correlated with a shift of NSCs into a multipotential state or apoptosis. These results provide new insights regarding the roles of FGFRs in diversification of NSC properties and initiation of neural lineage-restricted differentiation.
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PMID:Self-renewing and differentiating properties of cortical neural stem cells are selectively regulated by basic fibroblast growth factor (FGF) signaling via specific FGF receptors. 1731 81

Non-Hodgkin lymphoma of the breast is a rare malignancy and present with almost equal frequency either as a primary or a secondary disease. Survival is poor in most cases of secondary breast lymphoma because of their advanced stage. We report a 35-year-old woman presenting with dyspnea as well as swelling, tenderness, and ruddiness in the left breast with non-cyclic pain for several months and maculopapular skin eruption in the same breast. Physical examination revealed fixed lymphadenopathies in both axillary regions. Radiologic evaluations (bilateral mammaograpy and ultrasonography) showed skin thickening in the left breast, asymmetrical densities in both breasts, and confirmed lymphadenopathies in the axillary regions. Excisional biopsies were performed to the left axillary lymph nodes and the breast skin eruptions. The histologic and immunohistochemical features were diagnosed as an ALK (-) anaplastic large cell lymphoma. A Computed Tomography examination was performed for staging the lymphoma and then chemotherapy was started. Thirty months after the diagnosis, the patient is still alive with disease. Because of the presence of systemic symptoms such as skin involvement and generalized lymphadenopathies (mediastinal, axillary or cervical), T cell lymphoma cases with breast involvement could mimic the clinical presentation of inflammatory breast carcinoma. Pathologic examination is needed for the correct diagnosis.
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PMID:Secondary involvement of the breast in T-cell non-Hodgkin lymphoma, an unusual example mimicking inflammatory breast carcinoma. 1908 16

When walking, step length provides critical information on traveled distance along the ongoing path [corrected] Little is known on the role that knowledge about body dimensions plays within this process. Here we directly addressed this question by evaluating whether changes in body proportions interfere with computation of traveled distance for targets located outside the reaching space. We studied locomotion and distance estimation in an achondroplastic child (ACH, 11 yr) before and after surgical elongation of the shank segments of both lower limbs and in healthy adults walking on stilts, designed to mimic shank-segment elongation. Kinematic analysis of gait revealed that dynamic coupling of the thigh, shank, and foot segments changed substantially as a result of elongation. Step length remained unvaried, in spite of the significant increase in total limb length ( approximately 1.5-fold). These relatively shorter strides resulted from smaller oscillations of the shank segment, as would be predicted by proportional increments in limb size and not by asymmetrical segmental increment as in the present case (length of thighs was not modified). Distance estimation was measured by walking with eyes closed toward a memorized target. Before surgery, the behavior of ACH was comparable to that of typically developing participants. In contrast, following shank elongation, the ACH walked significantly shorter distances when aiming at the same targets. Comparable changes in limb kinematics, stride length, and estimation of traveled distance were found in adults wearing on stilts, suggesting that path integration errors in both cases were related to alterations in the intersegmental coordination of the walking limbs. The results are consistent with a dynamic locomotor body schema used for controlling step length and path estimation, based on inherent relationships between gait parameters and body proportions.
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PMID:Changes in the limb kinematics and walking-distance estimation after shank elongation: evidence for a locomotor body schema? 1909 16

An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-beta1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-beta1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-beta1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1-dependent manner. Although the invasion induced by HRG-beta1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-beta1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands.
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PMID:The EGF/CSF-1 paracrine invasion loop can be triggered by heregulin beta1 and CXCL12. 1929 85

A new class of dendron-like polypeptide/linear poly(epsilon-caprolactone) block copolymers with asymmetrical topology (i.e., dendron-like poly(gamma-benzyl-l-glutamate)/linear PCL copolymers having 2(m) PBLG branches, m = 0, 1, 2, and 3; denoted as PCL-Dm-PBLG) was for the first time synthesized via the combination of controlled ring-opening polymerization (ROP) of epsilon-caprolactone, click chemistry, and the ROP of gamma-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA). The linear hydroxyl-terminated PCL (PCL-OH) was synthesized by controlled ROP of epsilon-caprolactone and then transformed into clickable azide-terminated PCL (PCL-N(3)). The PCL-N(3) precursor was further click conjugated with propargyl focal point PAMAM-typed dendrons (i.e., Dm having 2(m) primary amine groups) to generate PCL-dendrons (PCL-Dm) using CuBr/PMDETA as catalyst in dimethylformamide solution at 35 degrees C. Finally, PCL-Dm was used as macroinitiator for the ROP of BLG-NCA monomer to produce the targeted PCL-Dm-PBLG block copolymers. Their molecular structures and physical properties were characterized in detail by FT-IR, NMR, matrix assisted laser desorption ionization time-of-flight mass spectrometry, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. To the best of our knowledge, this is the first report that describes the synthesis of dendron-like polypeptide/linear PCL block copolymers with asymmetrical topology via the combination of ROP and click chemistry. Consequently, this provides a versatile strategy for the synthesis of biodegradable and biomimetic dendron-like polypeptide-based biohybrids.
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PMID:Versatile strategy for the synthesis of dendronlike polypeptide/linear poly(epsilon-caprolactone) block copolymers via click chemistry. 1932 56


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