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Distinct Domains (distinct + domain)
Selected AbstractsDorsally derived BMP4 inhibits the induction of spinal cord oligodendrocyte precursorsJOURNAL OF NEUROCHEMISTRY, Issue 2002R. H. Miller During development oligodendrocyte precursors arise in a distinct domain of the ventral ventricular zone in the spinal cord that they share with motor neurons. The localized appearance of oligodendrocyte and motor neuron precursors is the result of local inductive signals including sonic hedgehog (Shh). Previous studies suggested that inhibitory signals from dorsal spinal cord act to sharpen the boundaries of the Shh induced region. Here we show that the dorsal spinal cord contains BMP4 during the developmental period when oligodendrocyte precursors first appear. In dissociated cultures of embryonic spinal cord cells, BMP4 competitively blocks the induction of oligodendrocyte precursors by Shh. Similarly, in embryonic slice preparations addition of BMP4 inhibited the appearance of oligodendrocyte precursors in the ventral spinal cord while addition of Shh enhanced their appearance. In vivo, transplantation of a BMP4 coated bead adjacent to the dorsal spinal cord inhibited ventral oligodendrogenesis while transplantation of a Shh coated bead enhanced ventral oligodendrogenesis. These data suggest that the initial localization of oligodendrocytes in the ventral spinal cord reflects the neutralization of dorsally-derived BMP4 inhibition by locally supplied Shh. [source] Organization of connections of the basal and accessory basal nuclei in the monkey amygdalaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000Eva Bonda Abstract PLEASE NOTE: Expression of Concern (EJN, 12:11, p4153) The present study investigated the intrinsic connections of the basal and accessory basal nuclei of the Macaca fascicularis monkey by means of the anterograde tracers Phaseolus vulgaris-leucoagglutinin (PHA-L) and biotinylated dextran amine (BDA). Analysis of the intranuclear connections of the basal nucleus indicates that there are five modules: dorsal, intermediate, ventral lateral, ventral medial and periamygdaloid sulcal cortex. The dorsal division projects to the intermediate division. Laterally, the intermediate division projects to the ventral lateral division and dorsal parts of the ventral medial division. Ventrally, the ventral lateral division projects to the ventral medial division and periamygdaloid sulcal cortex, which appears to constitute a medial extension of the basal nucleus onto the cortical surface of the amygdala. Medially, the ventral medial division projects to the intermediate and dorsal divisions. Thus, the connections between these modules form functional microcolumns within the nucleus with distinct patterns of information flow that are dorsal to ventral laterally, lateral to medial ventrally, and ventral to dorsal medially. Observations on the intranuclear connections of the accessory basal nucleus suggest that they are organized into two relatively distinct domains: the dorsal division projects to the ventral division and the ventral division projects primarily to the ventromedial division. Projections to other amygdaloid areas originate in select divisions of the basal and accessory basal nuclei, and are topographically distributed. The organization of intrinsic connections of the basal nuclei correlates with specific amygdalo-cortical connections and suggests that extensive convergence of information takes place within the amygdala, which potentially influences activity at both the temporal and parietal pathways and hippocampal fields. [source] Two conserved domains in regulatory B subunits mediate binding to the A subunit of protein phosphatase 2AFEBS JOURNAL, Issue 2 2002Xinghai Li Protein phosphatase 2A (PP2A) is an abundant heterotrimeric serine/threonine phosphatase containing highly conserved structural (A) and catalytic (C) subunits. Its diverse functions in the cell are determined by its association with a highly variable regulatory and targeting B subunit. At least three distinct gene families encoding B subunits are known: B/B55/CDC55, B,/B56/RTS1 and B,/PR72/130. No homology has been identified among the B families, and little is known about how these B subunits interact with the PP2A A and C subunits. In vitro expression of a series of B56, fragments identified two distinct domains that bound independently to the A subunit. Sequence alignment of these A subunit binding domains (ASBD) identified conserved residues in B/B55 and PR72 family members. The alignment successfully predicted domains in B55 and PR72 subunits that similarly bound to the PP2A A subunit. These results suggest that these B subunits share a common core structure and mode of interaction with the PP2A holoenzyme. [source] E1-Ngn2/Cre is a new line for regional activation of Cre recombinase in the developing CNSGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 4 2004Joachim Berger Abstract We generated a transgenic mouse line named E1-Ngn2/Cre that expresses Cre recombinase and GFP under the control of the E1 enhancer element of the gene Ngn2 (Scardigli et al.: Neuron 31:203,217, 2001). Cre-recombinase activity and GFP fluorescence are consistent with the reported expression pattern controlled by the E1-Ngn2 enhancer. Recombination was detected in the progenitor domains p1 and p2 in the ventricular zone of the neural tube and in distinct domains of the pretectum, the dorsal and ventral thalamus, the tegmentum of the mesencephalon, and the hindbrain. In the developing cortex, Cre-recombinase activity is confined to a subpopulation of progenitors predominantly in the region of the ventral and lateral pallium. The E1-Ngn2/Cre mouse line thus provides an excellent novel tool for a region-specific conditional mutagenesis in the developing CNS. genesis 40:195,199, 2004. © 2004 Wiley-Liss, Inc. [source] The ABCA1 cholesterol transporter associates with one of two distinct dystrophin-based scaffolds in Schwann cellsGLIA, Issue 6 2008Douglas E. Albrecht Abstract Cytoskeletal scaffolding complexes help organize specialized membrane domains with unique functions on the surface of cells. In this study, we define the scaffolding potential of the Schwann cell dystrophin glycoprotein complex (DGC) by establishing the presence of four syntrophin isoforms, (,1, ,1, ,2, and ,2), and one dystrobrevin isoform, (,-dystrobrevin-1), in the abaxonal membrane. Furthermore, we demonstrate the existence of two separate DGCs in Schwann cells that divide the abaxonal membrane into spatially distinct domains, the DRP2/periaxin rich plaques and the Cajal bands that contain Dp116, utrophin, ,-dystrobrevin-1 and four syntrophin isoforms. Finally, we show that the two different DGCs can scaffold unique accessory molecules in distinct areas of the Schwann cell membrane. Specifically, the cholesterol transporter ABCA1, associates with the Dp116/syntrophin complex in Cajal bands and is excluded from the DRP2/periaxin rich plaques. © 2008 Wiley-Liss, Inc. [source] Aldehyde-Amine Chemistry Enables Modulated Biosealants with Tissue-Specific AdhesionADVANCED MATERIALS, Issue 32-33 2009Natalie Artzi The interfacial regions between PEG: dextran-based adhesive sealant and excised rat heart, lung, liver, and duodenum tissues exhibit three distinct domains; target tissue (red and blue), bulk material (green), and an adhesive regime interposed between the two. The variation in adhesive regime morphology when applied to different tissues provides a rational approach for the engineering of application-specific surgical sealants. [source] Mucosal tissue transglutaminase expression in celiac diseaseJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2009Vincenzo Villanacci Abstract Tissue transglutaminase (tTG) plays an important role in celiac disease pathogenesis and antibodies to tTG are a diagnostic marker of gluten-sensitive enteropathy. The aim of this study was to investigate the localization of tTG in the duodenal mucosa in control tissues and in different histological stages of celiac disease by using a commercial and a novel set of anti-tTG monoclonal antibodies, to see whether this assessment can be useful for diagnostic purpose. The distribution of tTG was firstly evaluated in 18 untreated celiac patients by using a commercial monoclonal antibody (CUB7402) against tissue transglutaminase enzyme and directed against the loop-core region of the enzyme. Thereafter, in further 30 untreated celiac patients we employed three newly characterized anti-tTG monoclonal antibodies produced against recombinant human-tTG. The epitopes recognized are located in three distinct domains of the protein corresponding to the core, C1 and C2 protein structure. Eleven age- and sex-matched patients with chronic duodenitis acted as controls. All subjects underwent upper endoscopy to obtain biopsy samples from the duodenum. Overall, we found that (i) tTG is equally expressed in CD at different stages of disease; (ii) tTG is expressed, at similar level, in CD and controls with duodenitis. Assessment of tTG level in biopsy samples by immunohistochemical methods is not useful in the clinical diagnostic work-up of CD. [source] Distinct regions of cyclinT1 are required for binding to CDK9 and for recruitment to the HIV-1 Tat/TAR complexJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S36 2001Alessandro Fraldi Abstract Tat-mediated activation of the HIV-1 promoter activity requires Tat-dependent recruitment of the cyclinT1/CDK9 complex (P-TEFb) to the transacting element (TAR) RNA. Tat interaction with the cyclinT1, the regulatory partner of CDK9, results in a specific recruitment of the heterodimer CycT1/CDK9 complex to TAR, whereby it promotes transcription elongation of the HIV-1 LTR-mediated transcription. Using the yeast two-hybrid protein interaction assay we analyzed the binding between cyclinT1 and CDK9. Moreover, using a modified three-hybrid yeast interaction system, we analyzed the recruitment of CycT1 to the Tat/TAR complex. The data presented here demonstrated that distinct domains of cyclinT1 interact with CDK9 and Tat/TAR in vivo. These findings will be instrumental for the designing of proper dominant-negative P-TEFb components capable to interfere with Tat function. J. Cell. Biochem. Suppl. 36: 247,253, 2001. © 2001 Wiley-Liss, Inc. [source] Behavioral and self-reported aggression as a function of domain-specific self-esteemAGGRESSIVE BEHAVIOR, Issue 1 2006Gregory D. Webster Abstract On the basis of a domain-specific theory of self-esteem, it was hypothesized that functionally distinct domains of self-esteem would predict aggression differentially. Participants completed self-report measures of self-perceived superiority, mate value, social inclusion, and global self-esteem, as well as of aggression. Self-assessed mate value emerged as a reliable, positive predictor, and social inclusion as a reliable inverse predictor, of self-reported hostility and aggression. In a subsequent laboratory experiment, in which participants had an opportunity to aggress against the source of positive or negative feedback about a personal essay that they had written, mate value again predicted increased aggression, whereas global self-esteem predicted decreased aggression. These main effects were moderated by the feedback manipulation, such that their respective simple effects were only present among participants that received negative feedback. Aggr. Behav. 00:1,11, 2005. © 2005 Wiley-Liss, Inc. [source] Characterization of polymetamorphism in the Austroalpine basement east of the Tauern Window using garnet isopleth thermobarometryJOURNAL OF METAMORPHIC GEOLOGY, Issue 6 2006F. GAIDIES Abstract Garnet in metapelites from the Wölz and Rappold Complexes of the Austroalpine basement east of the Tauern Window typically shows two distinct growth zones. A first garnet generation usually forms the cores of garnet porphyroblasts and is separated by a prominent microstructural and chemical discontinuity from a second garnet generation, which forms rims of variable width. Whereas the rims were formed during the Eo-Alpine metamorphic overprint, the garnet cores represent remnants of at least two pre-Eo-Alpine metamorphic events. The pressure and temperature estimates obtained from garnet isopleth thermobarometry applied to the first growth increments of the pre-Eo-Alpine garnet cores from the Wölz and Rappold Complexes cluster into two distinct domains: (i) in the Wölz Complex, incipient growth of the first-generation garnet occurred at 4 ± 0.5 kbar and 535 ± 20 °C, (ii) in the Rappold Complex, incipient growth of the oldest garnet cores took place at 5.3 ± 0.3 kbar and 525 ± 15 °C. The Eo-Alpine garnet generation started to grow at 6.5 ± 0.5 kbar and 540 ± 10 °C. According to radiometric dating, the low-pressure garnet from the Wölz complex was formed during a Permian metamorphic event. The first-generation garnet of the Rappold Complex is probably of Variscan age. [source] Synaptic localization of neuroligin 2 in the rodent retina: Comparative study with the dystroglycan-containing complexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2010Leona Lui Abstract Several recent studies have shown that neuroligin 2 (NL2), a component of the cell adhesion neurexins,neuroligins complex, is localized postsynaptically at hippocampal and other inhibitory synapses throughout the brain. Other studies have shown that components of the dystroglycan complex are also localized at a subset of inhibitory synapses and are coexpressed with NL2 in brain. These data prompted us to undertake a comparative study between the localization of NL2 and the dystroglycan complex in the rodent retina. First, we determined that NL2 mRNA is expressed both in the inner and in the outer nuclear layers. Second, we found that NL2 is localized both in the inner and in the outer synaptic plexiform layers. In the latter, the horseshoe-shaped pattern of NL2 and its extensive colocalization with RIM2, a component of the presynaptic active zone at ribbon synapses, argue that NL2 is localized presynaptically at photoreceptor terminals. Third, comparison of NL2 and the dystroglycan complex distribution patterns reveals that, despite their coexpression in the outer plexiform layer, they are spatially segregated within distinct domains of the photoreceptor terminals, where NL2 is selectively associated with the active zone and the dystroglycan complex is distally distributed in the lateral regions. Finally, we report that the dystroglycan deficiency in the mdx3cv mouse does not alter NL2 localization in the outer plexiform layer. These data show that the NL2- and dystroglycan-containing complexes are differentially localized in the presynaptic photoreceptor terminals and suggest that they may serve distinct functions in retina. © 2009 Wiley-Liss, Inc. [source] Frontloading Mitigation: The "Legal" and the "Human" in Death Penalty DefenseLAW & SOCIAL INQUIRY, Issue 1 2010Jesse Cheng The bifurcation of capital trials into determinations of guilt and sentencing presents defense advocates with what seem to be two distinct domains of knowledge,one apparently "legal" in character, the other "human." But this epistemological division is actually not so clear in practice. This article dissects the procedural and strategic mechanisms through which these two domains unsettle and reconstitute the other. I provide a historical, empirically grounded account that explicitly articulates the connections between developments in legal procedure, prevailing standards of care concerning the need to conduct humanistic investigations of mitigating factors, and the on-the-ground trial practice of "frontloading" as a defense strategy. Drawing from documentary research, interview data with leading capital defense practitioners, and analytical observations based on my own experience as a mitigation specialist, this article presents itself as a case study of the processes of mutually constitutive rupturing that reconfigure the categories of the legal and the human. [source] Dimer-induced signal propagation in Spo0AMOLECULAR MICROBIOLOGY, Issue 3 2004K. Muchová Summary Spo0A, the response regulator protein controlling the initiation of sporulation in Bacillus, has two distinct domains, an N-terminal phosphoacceptor (or receiver) domain and a C-terminal DNA-binding (or effector) domain. The phosphoacceptor domain mediates dimerization of Spo0A on phosphorylation. A comparison of the crystal structures of phosphorylated and unphosphorylated response regulators suggests a mechanism of activation in which structural changes originating at the phosphorylatable aspartate extend to the ,4,5,5 surface of the protein. In particular, the data show an important role in downstream signalling for a conserved aromatic residue (Phe-105 in Spo0A), the conformation of which alters upon phosphorylation. In this study, we have prepared a Phe-105 to Ala mutant to probe the contribution of this residue to Spo0A function. We have also made an alanine substitution of the neighbouring residue Tyr-104 that is absolutely conserved in the Spo0As of spore-forming Bacilli. The spo0A(Y104A) and spo0A(F105A) alleles severely impair sporulation in vivo. In vitro phosphorylation of the purified proteins by phosphoramidate is unaffected, but dimerization and DNA binding are abolished by the mutations. We have identified intragenic suppressor mutations of spo0A(F105A) and shown that these second-site mutations in the purified proteins restore phosphorylation-dependent dimer formation. Our data support a model in which dimerization and signal transduction between the two domains of Spo0A are mediated principally by the ,4,5,5 signalling surface in the receiver domain. [source] An amino-terminal domain of Enterococcus faecalis aggregation substance is required for aggregation, bacterial internalization by epithelial cells and binding to lipoteichoic acidMOLECULAR MICROBIOLOGY, Issue 4 2004Christopher M. Waters Summary Aggregation substance (AS), a plasmid-encoded surface protein of Enterococcus faecalis, plays important roles in virulence and antibiotic resistance transfer. Previous studies have suggested that AS-mediated aggregation of enterococcal cells could involve the binding of this protein to cell wall lipoteichoic acid (LTA). Here, a method to purify an undegraded form of Asc10, the AS of the plasmid pCF10, is described. Using this purified protein, direct binding of Asc10 to purified E. faecalis LTA was demonstrated. Equivalent binding of Asc10 to LTA purified from INY3000, an E. faecalis strain that is incapable of aggregation, was also observed. Surprisingly, mutations in a previously identified aggregation domain from amino acids 473 to 683 that abolished aggregation had no effect on LTA binding. In frame deletion analysis of Asc10 was used to identify a second aggregation domain located in the N-terminus of the protein from amino acids 156 to 358. A purified Asc10 mutant protein lacking this domain showed reduced LTA binding, while a purified N-terminal fragment from amino acids 44,331 had high LTA binding. Like the previously described aggregation domain, the newly identified Asc10(156,358) aggregation domain was also required for efficient internalization of E. faecalis into HT-29 enterocytes. Thus, Asc10 possess two distinct domains required for aggregation and eukaryotic cell internalization: an N-terminal domain that promotes binding to LTA and a second domain located near the middle of the protein. [source] The N-terminal region of Pseudomonas type III effector AvrPtoB elicits Pto-dependent immunity and has two distinct virulence determinantsTHE PLANT JOURNAL, Issue 4 2007Fangming Xiao Summary Resistance to bacterial speck disease in tomato is activated by the physical interaction of the host Pto kinase with either of the sequence-dissimilar type III effector proteins AvrPto or AvrPtoB (HopAB2) from Pseudomonas syringae pv. tomato. Pto-mediated immunity requires Prf, a protein with a nucleotide-binding site and leucine-rich repeats. The N-terminal 307 amino acids of AvrPtoB were previously reported to interact with the Pto kinase, and we show here that this region (AvrPtoB1-307) is sufficient for eliciting Pto/Prf-dependent immunity against P. s. pv. tomato. AvrPtoB1-307 was also found to be sufficient for a virulence activity that enhances ethylene production and increases growth of P. s. pv. tomato and severity of speck disease on susceptible tomato lines lacking either Pto or Prf. Moreover, we found that residues 308,387 of AvrPtoB are required for the previously reported ability of AvrPtoB to suppress pathogen-associated molecular patterns-induced basal defenses in Arabidopsis. Thus, the N-terminal region of AvrPtoB has two structurally distinct domains involved in different virulence-promoting mechanisms. Random and targeted mutagenesis identified five tightly clustered residues in AvrPtoB1-307 that are required for interaction with Pto and for elicitation of immunity to P. s. pv. tomato. Mutation of one of the five clustered residues abolished the ethylene-associated virulence activity of AvrPtoB1-307. However, individual mutations of the other four residues, despite abolishing interaction with Pto and avirulence activity, had no effect on AvrPtoB1-307 virulence activity. None of these mutations affected the basal defense-suppressing activity of AvrPtoB1-387. Based on sequence alignments, estimates of helical propensity, and the previously reported structure of AvrPto, we hypothesize that the Pto-interacting domains of AvrPto and AvrPtoB1-307 have structural similarity. Together, these data support a model in which AvrPtoB1-307 promotes ethylene-associated virulence by interaction not with Pto but with another unknown host protein. [source] Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenonARTHRITIS & RHEUMATISM, Issue 9 2002Peter A. Merkel Objective To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients. Methods Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data. Results Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18,82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 ± 2.33 (mean ± SD) daily RP attacks (range 0.8,14.6), with a duration of 82.1 ± 91.6 minutes/attack. RCS for RP activity (possible range 0,10) was 4.30 ± 1.92. HAQ scores (0,3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33,0.76). Conclusion Our findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2). [source] Enzymatic Release of a Surface-Adsorbed RGD Therapeutic from a Cleavable Peptide AnchorCHEMMEDCHEM, Issue 11 2008Steven Implanted medical devices inevitably promote inflammation of the surrounding tissue. A method for enzymatically triggered localized drug delivery would have marked benefits in dealing with this response. Herein we present a rationally designed peptide coating for use with medical devices such as stents, that contains three distinct domains: 1),an implant-adsorptive sequence, 2),an enzymatically cleavable release mechanism, and 3),a therapeutic to be delivered. [source] | ||||||||||||||||