scholarly journals Molecular Regions Controlling the Activity of Cng Channels

2001 ◽  
Vol 118 (2) ◽  
pp. 183-192 ◽  
Author(s):  
Holger Möttig ◽  
Jana Kusch ◽  
Thomas Zimmer ◽  
Annette Scholle ◽  
Klaus Benndorf
Keyword(s):  
Energy Difference ◽  
Core Region ◽  
The Other ◽  
Wild Type ◽  
The Core ◽  
Retinal Photoreceptors ◽  
Channel Opening ◽  
Main Portion ◽  
The Difference ◽  
Α Subunits

The α subunits of CNG channels of retinal photoreceptors (rod) and olfactory neurons (olf) are proteins that consist of a cytoplasmic NH2 terminus, a transmembrane core region (including the segments S1–S6), and a cytoplasmic COOH terminus. The COOH terminus contains a cyclic nucleotide monophosphate binding domain NBD) that is linked by the C-linker (CL) to the core region. The binding of cyclic nucleotides to the NBD promotes channel opening by an allosteric mechanism. We examined why the sensitivity to cGMP is 22 times higher in olf than in rod by constructing chimeric channels and determining the [cGMP] causing half maximum channel activity (EC50). The characteristic difference in the EC50 value between rod and olf was introduced by the NH2 terminus and the core-CL region, whereas the NBD showed a paradoxical effect. The difference of the free energy difference Δ(ΔG) was determined for each of these three regions with all possible combinations of the other two regions. For rod regions with respect to corresponding olf regions, the open channel conformation was destabilized by the NH2 terminus (Δ(ΔG) = −1.0 to −2.0 RT) and the core-CL region (Δ(ΔG) = −2.0 to −2.9 RT), whereas it was stabilized by the NBD (Δ(ΔG) = 0.3 to 1.1 RT). The NH2 terminus deletion mutants of rod and olf differed by Δ(ΔG) of only 0.9 RT, whereas the wild-type channels differed by the much larger value of 3.1 RT. The results show that in rod and olf, the NH2 terminus, the core-CL region, and the NBD differ by characteristic Δ(ΔG) values that do not depend on the specific composition of the other two regions and that the NH2 terminus generates the main portion of Δ(ΔG) between the wild-type channels.

128 Differences in PRRSV Resilience for Reproductive Performance Between Landrace and Duroc Sows

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 18-19
Author(s):  
Felipe Hickmann ◽  
José Braccini Neto ◽  
Luke M Kramer ◽  
Kent A Gray ◽  
Yijian Huang ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Mixed Model ◽  
Performance Data ◽  
The Other ◽  
Wild Type ◽  
Prrs Virus ◽  
The Difference ◽  
The Impact

Abstract Studies on differences in resilience to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) between breeds are scarce in the literature. Thus, the objective of this work was to assess PRRSV resilience in PRRSV wild-type infected sows from two breeds. Farrowing data included 2546 and 2522 litters from 894 Duroc and 813 Landrace sows, respectively, which were housed together and experienced the same PRRSV outbreak. Traits used for this study were number of piglets born alive (NBA), number born dead (NBD), total number born (TNB), and number weaned (NW). The impact of PRRSV infection was evaluated by comparing the reproductive performance of breeds between PRRS phases (pre-PRRS, PRRS, and post-PRRS). PRRS phases were defined based on the reproductive performance data. NBA, NBD, and NW were analyzed as a proportion of TNB using a Poisson mixed model. Pre-defined contrasts were used to evaluate the effect of breed on PRRSV resilience and on return to PRRSV-free performance, representing the differences between breeds for the difference between pre-PRRS and PRRS phases, and pre-PRRS and post-PRRS phases, respectively. There was a significant (P ≤ 0.003) interaction between PRRS phase and breed for all traits, as shown in Table 1. In general, reproductive performance reduced from pre-PRRS to PRRS, and then increased from PRRS to post-PRRS, as expected. The resilience contrast was significant for all traits (P ≤ 0.003). In all cases, the drop in percent reproductive performance from pre-PRRS to PRRS was lower for Duroc than for Landrace, indicating that Duroc sows have greater PRRSV resilience than Landrace sows. The return to PRRSV-free performance contrast had a trending effect for NBD (P = 0.055), and it was not significant for the other traits (P ≥ 0.515). These results indicate that Duroc sows have overall greater phenotypic PRRSV resilience for reproductive performance than Landrace sows.

An alkaline phosphatase mutant of Pseudomonas aeruginosa. 1. Effects of regulatory, structural, and environmental shifts on enzyme function

1978 ◽  
Vol 24 (4) ◽  
pp. 427-432 ◽  
Author(s):  
M. L. Marceau-Day ◽  
D. F Day ◽  
J. M. Ingram
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Alkaline Phosphatase ◽  
Core Region ◽  
Significant Activity ◽  
Wild Type ◽  
Glycerol Phosphate ◽  
The Core ◽  
Nitrophenyl Phosphate ◽  
Mutant Cells

An alkaline phosphatase mutant of Pseudomonas aeruginosa exhibiting both regulatory and catalytic changes was isolated. Under repression conditions (i.e. high inorganic phosphate (Pi)) the mutant culture produced an alkaline phosphatase (APase) displaying significant activity against both β-glycerol phosphate (βGP) and p-nitrophenyl phosphate (pNPP), while the wild type displayed no activity directed towards these substrates under the same conditions. In vivo, the mutant enzyme's ratio of specific activities was 45:1 in favour of βGP versus pNPP, whereas this ratio was reversed to 1:9 βGP versus pNPP for the same enzyme isolated from mutant cells. In addition, the kinetic parameters and stability requirements for the mutant-derived enzyme was altered in comparison with those of the wild type. A study of lipopolysaccharide(LPS) preparations from both the mutant and wild type indicated the mutant to be deficient in the core region of its LPS. The authors propose that the modifications in the catalytic activity of the mutant enzyme, demonstrated in vivo, are due to a change in the enzyme's microenvironment.

Manipulated Agents

2019 ◽  
Author(s):  
Alfred R. Mele
Keyword(s):  
Moral Responsibility ◽  
Significant Role ◽  
Thought Experiments ◽  
The Other ◽  
Value Systems ◽  
Psychological State ◽  
Important Lesson ◽  
The Core ◽  
The Difference ◽  
Historical Difference

Thought experiments featuring manipulated agents and designed agents have played a significant role in the literature on moral responsibility. What can we learn from thought experiments of this kind about the nature of moral responsibility? That is this book’s primary question. An important lesson lies at the core of its answer: Moral responsibility for actions has a historical dimension of a certain kind. A pair of agents whose current nonhistorical properties are very similar and who perform deeds of the same kind may nevertheless be such that one is morally responsible for the deed whereas the other is not, and what makes the difference is a difference in how they came to be as they are at that time—that is, a historical difference. Imagine that each of these agents attempts to assassinate someone. Depending on the details of the cases, it may be that one of these agents is morally responsible for the attempt whereas the other is not, because one of them was manipulated in a certain way into being in the psychological state that issues in the behavior whereas the other agent came to be in that state under his own steam. A variety of thought experiments are considered. They include stories about agents whose value systems are radically altered by manipulators, vignettes featuring agents who are built from scratch, and scenarios in which agents magically come into being with full psychological profiles.

Effects of Core Material on Extrudability of Cu/Pure Al, Cu/Al3003 Clad Composites by Indirect Extrusion

2005 ◽  
Vol 475-479 ◽  
pp. 967-970 ◽  
Author(s):  
Taek Kyun Jung ◽  
Hyouk Chon Kwon ◽  
Sung Chul Lim ◽  
Young Sup Lee ◽  
Mok Soon Kim
Keyword(s):  
Diffusion Layer ◽  
Bonding Strength ◽  
Pure Aluminum ◽  
Extrusion Ratio ◽  
The Other ◽  
Core Material ◽  
Diffusion Layer Thickness ◽  
The Core ◽  
The Difference ◽  
Sheath Material

We investigated about the effects of core material(Pure Al, Al3003) on extrudability such as the maximum extrusion ratio and the bonding strength of Copper Clad Aluminum(CCA) by indirect extrusion. As a results of this experiment, the maximum extrusion ratio of Cu/Al3003 was 38, which was larger than 21.39 of Cu/Al(Cu/pure Al). It was because that the difference of flow stress between copper as the sheath material and Al3003 as the core material was smaller than that of between copper and pure aluminum under the same extrusion temperature of 623K. The bonding strength gradually increased when the extrusion ratio increased, on the other hand, the bonding strength of Cu/Al3003 was higher than that of Cu/Al under same extrusion conditions. The diffusion layer thickness that affected bonding strength was not affected by the kind of core material, but it gradually increased when the extrusion ratio increased. It was thought that Cu/Al3003 had a more intimate diffusion layer than Cu/Al had because the extrusion pressure of Cu/Al3003 was higher than that of Cu/Al under the same extrusion conditions.

Actually and in fact in American English: a data-based analysis

2000 ◽  
Vol 4 (2) ◽  
pp. 243-268 ◽  
Author(s):  
Sun-Young Oh
Keyword(s):  
American English ◽  
The Other ◽  
The Core ◽  
The Difference ◽  
Core Meaning

Actually and in fact have been generally regarded as interchangeable without leading to any significant differences in the meaning of the containing utterances: as a result, no serious attempt has been made to discover potential differences between the two. The present study focuses on the differences as well as the similarities between actually and in fact in their distribution and use in spoken and written American English. Based upon an analysis of tokens from the Switchboard Corpus and the Brown Corpus, I propose that `unexpectedness’ is the core meaning shared by actually and in fact, and that the difference between the two lies in the typical association of each with one or the other way of signalling ‘unexpectedness’. The study also shows that in real discourse contexts, actually and in fact develop a number of different uses that are more or less remote from this core meaning.

The Human Alpha Hemoglobin Stabilizing Protein (AHSP) Gene Locus in EKLF-Deficient Erythroid Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1740-1740
Author(s):  
Andre M. Pilon ◽  
Dewang Zhou ◽  
Mitchell J. Weiss ◽  
Timothy M. Townes ◽  
David M. Bodine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fetal Liver ◽  
Core Promoter ◽  
The Other ◽  
Wild Type ◽  
The Core ◽  
Fetal Liver Cells ◽  
Globin Promoter ◽  
And Control ◽  
Deficient Mice

Abstract AHSP is an erythroid-specific protein that complexes with free α-hemoglobin, protecting it from precipitation. AHSP has been proposed as a modifier gene in β thalassemia and as a candidate gene for unexplained Heinz body anemias, thus understanding its regulation may lead to novel therapies for these disorders. Identified as an erythroid-specific, GATA-1 inducible gene, decreased AHSP mRNA has been found in the fetal livers of mice deficient in the erythroid transcription factor EKLF by both microarray and RNA subtraction analysis. In fetal livers from d13.5 EKLF-deficient mice, AHSP/α-globin mRNA ratios were decreased to 11–16% of wild type by RT-PCR and RPA. In the same fetal livers, no AHSP protein was detected on Western blots with a MoAB against AHSP. EKLF interacts with the proximal CACCC box of the β-globin gene promoter, establishing local chromatin structure and directing high-level β-globin transcription. We hypothesized that chromatin across the AHSP locus would be perturbed in erythroid cells from EKLF-deficient mice. We performed DNase I hypersensitive site (HS) mapping and chromatin immunoprecipitation (ChIP) analysis using wild type and EKLF deficient fetal liver cells. A strong HS was identified in the AHSP 5′ flanking DNA in the core promoter region, that was absent in day 13.5 fetal liver DNA from EKLF-deficient mice. Fine mapping placed this 5′ HS over a CACCC site in the core AHSP promoter. ChIP across the entire AHSP locus with d13.5 fetal liver chromatin identified 2 regions of hyperacetylation of histones H3 and H4 in wild type mice, one corresponding to the 5′ HS and the other 3′ to the AHSP coding sequence. Both of these hyperacetylated regions were hypoacetylated in EKLF-deficient fetal liver cells. ChIP across the AHSP locus with chromatin obtained from mice with an HA tag knocked into the 3′ end of the EKLF gene identified a peak of EKLF binding extending from the 5′HS to intron one, peaking over the core promoter CACCC site. The sequence of this region (ACCCACCCT) has a single mismatch compared to the EKLF consensus site (CCNCNCCCN). Using the AHSP CACCC site as probe in mobility shift assays with rEKLF protein yielded a complex that migrated at the same mobility as a complex obtained with a control β-globin promoter CACCC site probe. Both AHSP and control β-globin complexes were effectively competed by an excess of unlabeled AHSP probe, unlabeled β-globin probe, or ELKF antiserum. Mutant AHSP CACCC probes did not form DNA-protein complexes nor did they effectively displace wild type AHSP CACCC or β-globin CACCC probes in competition assays. Probes with the AHSP CACCC site mutated to the β-globin sequence (A to C) or the other 2 possibilities (A to G, A to T) yielded complexes comparable to wild type AHSP and control β-globin CACCC probes. In transfection assays in K562 cells, an AHSP promoter-luciferase reporter plasmid was transactivated by an EKLF expression plasmid to a degree comparable to a β-globin promoter-luciferase plasmid. These results support the hypotheses that the hemolytic anemia in EKLF-deficient mice is exacerbated by decreased AHSP expression and that EKLF acts as a transcription factor and a chromatin modulator for genes other than β-globin. Our data also support the hypothesis that AHSP and EKLF may be modifier genes for the β-thalassemia syndromes.

scholarly journals A Three-Way Clustering Method Based on Ensemble Strategy and Three-Way Decision

Information ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 59 ◽  
Author(s):  
Pingxin Wang ◽  
Qiang Liu ◽  
Gang Xu ◽  
Kangkang Wang
Keyword(s):  
Clustering Algorithm ◽  
Core Region ◽  
Data Sets ◽  
Clustering Methods ◽  
The Core ◽  
Ensemble Strategy ◽  
Hard Clustering ◽  
The Difference ◽  
Human Problem ◽  
Specific Cluster

Three-way decision is a class of effective ways and heuristics commonly used in human problem solving and information processing. As an application of three-way decision in clustering, three-way clustering uses core region and fringe region to represent a cluster. The identified elements are assigned into the core region and the uncertain elements are assigned into the fringe region in order to reduce decision risk. In this paper, we propose a three-way clustering algorithm based on the ideas of cluster ensemble and three-way decision. In the proposed method, we use hard clustering methods to produce different clustering results and labels matching to align all clustering results to a given order. The intersection of the clusters with the same labels are regarded as the core region. The difference between the union and the intersection of the clusters with the same labels are regarded as the fringe region of the specific cluster. Therefore, a three-way clustering is naturally formed. The results on UCI data sets show that such a strategy is effective in improving the structure of clustering results.

Structure of the Lipopolysaccharide Core Region of the Bacteria of the Genus Proteus

2002 ◽  
Vol 55 (2) ◽  
pp. 61 ◽  
Author(s):  
E. Vinogradov ◽  
Z. Sidorczyk ◽  
Y. A. Knirel
Keyword(s):  
Core Region ◽  
Core Structure ◽  
The Other ◽  
Carboxyl Group ◽  
Open Chain ◽  
Covalent Linkage ◽  
The Core ◽  
New Type ◽  
First Time ◽  
Chain Form

The lipopolysaccharide (LPS) core structure was studied in seven rough strains of Proteus and 26 smooth strains belonging to various Proteus O-serogroups. All LPSs share a common heptasaccharide fragment, which includes two Kdo, three Hep, one Glc, and one GalA residue. Core structures differ between strains and within each strain in the presence of a variety of additional monosaccharides and non-sugar substituents. In many strains, the LPS includes a cyclic acetal of GalNAc in the open-chain form, which builds up a new type of linkage between monosaccharides. The covalent linkage of aliphatic polyamines, e.g. putrescine and spermidine, to the LPS was confirmed for the first time and the location of the amines at the carboxyl group of a GalA residue established. Analyses revealed peculiar features of the core structure, which are characteristic of P. mirabilis on one hand and P. vulgaris and P. penneri on the other hand.

scholarly journals Genotypes and Characteristics of Phenamacril-Resistant Mutants in Fusarium asiaticum

Plant Disease ◽  
2016 ◽  
Vol 100 (8) ◽  
pp. 1754-1761 ◽  
Author(s):  
Bin Li ◽  
Zhitian Zheng ◽  
Xiumei Liu ◽  
Yiqiang Cai ◽  
Xuewei Mao ◽  
...  
Keyword(s):  
Point Mutations ◽  
Core Region ◽  
Wild Type ◽  
Head Blight ◽  
Pathogen Population ◽  
Resistance Level ◽  
The Core ◽  
Fusarium Asiaticum ◽  
Resistant Mutants ◽  
Moderate Resistance

Fusarium asiaticum is a critical pathogen of Fusarium head blight (FHB) in the southern part of China. The fungicide phenamacril has been extensively used for controlling FHB in recent years, which reduced both FHB severity and mycotoxin production. Our previous report indicated that resistance of F. asiaticum to phenamacril was related to mutations in myosin5. A recent article revealed that the resistance level of phenamacril-resistant mutants was associated with the genotypes of myosin5 in these mutants. In total, we obtained 239 resistant isolates by fungicide domestication, and 82 resistant mutants were randomly selected for further study. Of these mutants, 25.6, 7.3, and 67.1% showed low resistance (LR), moderate resistance (MR), and high resistance (HR), respectively, to phenamacril determined by 50% effective concentration values. Point mutations A135T, V151M, P204S, I434M, A577T, R580G/H, or I581F led to LR. Point mutations S418R, I424R, and A577G were responsible for MR and point mutations K216R/E, S217P/L, or E420K/G/D conferred HR. Interestingly, all of the mutations concentrated in the myosin5 motor domain and mutations conferring HR occurred at codon 217 and 420, which we called the core region. Homology modeling revealed that mutations far from the core region led to a lower resistance degree. Phenotype assays revealed that the most highly resistant mutants did not significantly change pathogenicity but decreased conidia production compared with the wild type, which may slow down the formation of the resistant pathogen population in the fields.

The Failure to Control and the Failure to Prevent, Repress and Submit: The Structure of Superior Responsibility under Article 28 icc Statute

2018 ◽  
Vol 18 (2) ◽  
pp. 275-303 ◽  
Author(s):  
Kazuya Yokohama
Keyword(s):  
International Criminal Court ◽  
International Criminal ◽  
Criminal Court ◽  
The Other ◽  
The Core ◽  
Controversial Topic ◽  
The Difference ◽  
The One ◽  
Superior Responsibility ◽  
The Relationship

In Article 28 of the statute of the International Criminal Court (icc), there appear to be two kinds of omission, namely, a failure to control on the one hand, and a failure to prevent, repress and submit on the other. However, the relationship between both omissions remains unclear so far. This is a controversial topic not only in the scholarly debate but also in the recent jurisprudence of the icc. The core question is whether both omissions need to be proved separately (twofold-failures approach), or whether only the proof of the latter omission could suffice for the superior to be held responsible (single-failure approach). These two approaches could lead to different conclusions as to several aspects of superior responsibility: the ‘number’ of omissions that must be proved and the requirement of causality, for example. This article addresses the difference between these two approaches and demonstrates which approach should be adopted.

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