scholarly journals Suppression of Viral Replication by Stress-Inducible GADD34 Protein via the Mammalian Serine/Threonine Protein Kinase mTOR Pathway

2007 ◽  
Vol 81 (20) ◽  
pp. 11106-11115 ◽  
Author(s):  
Kahori Minami ◽  
Yukihiro Tambe ◽  
Ryosuke Watanabe ◽  
Takahiro Isono ◽  
Masataka Haneda ◽  
...  
Keyword(s):  
Viral Replication ◽  
Critical Role ◽  
Cellular Protein ◽  
Mtor Pathway ◽  
The Other ◽  
Mtor Signaling Pathway ◽  
Wild Type ◽  
Other Hand ◽  
Vesicular Stomatitis ◽  
Pathway Inhibition

ABSTRACT GADD34 is a protein that is induced by a variety of stressors, including DNA damage, heat shock, nutrient deprivation, energy depletion, and endoplasmic reticulum stress. Here, we demonstrated that GADD34 induced by vesicular stomatitis virus (VSV) infection suppressed viral replication in wild-type (WT) mouse embryo fibroblasts (MEFs), whereas replication was enhanced in GADD34-deficient (GADD34-KO) MEFs. Enhanced viral replication in GADD34-KO MEFs was reduced by retroviral gene rescue of GADD34. The level of VSV protein expression in GADD34-KO MEFs was significantly higher than that in WT MEFs. Neither phosphorylation of eIF2α nor cellular protein synthesis was correlated with viral replication in GADD34-KO MEFs. On the other hand, phosphorylation of S6 and 4EBP1, proteins downstream of mTOR, was suppressed by VSV infection in WT MEFs but not in GADD34-KO MEFs. GADD34 was able to associate with TSC1/2 and dephosphorylate TSC2 at Thr1462. VSV replication was higher in TSC2-null cells than in TSC2-expressing cells, and constitutively active Akt enhanced VSV replication. On the other hand, rapamycin, an mTOR inhibitor, significantly suppressed VSV replication in GADD34-KO MEFs. These findings demonstrate that GADD34 induced by VSV infection suppresses viral replication via mTOR pathway inhibition, indicating that cross talk between stress-inducible GADD34 and the mTOR signaling pathway plays a critical role in antiviral defense.

Eternal Guests, Mimics, and Dönme: The Place of German and Turkish Jews in Modern Turkey

2007 ◽  
Vol 37 ◽  
pp. 5-30 ◽  
Author(s):  
Kader Konuk
Keyword(s):  
Critical Role ◽  
The Other ◽  
Turkish Republic ◽  
German Jews ◽  
Other Hand ◽  
Turkish Culture ◽  
The Status ◽  
Modern Turkey ◽  
The One ◽  
European Civilization

AbstractThe place of Jews was highly ambiguous in the newly founded Turkish Republic: In 1928 an assimilationist campaign was launched against Turkish Jews, while only a few years later, in 1933, German scholars—many of them Jewish—were taken in so as to help Europeanize the nation. Turkish authorities regarded the emigrants as representatives of European civilization and appointed scholars like Erich Auerbach to prestigious academic positions that were vital for redefining the humanities in Turkey. This article explores the country's twofold assimilationist policies. On the one hand, Turkey required of its citizens—regardless of ethnic or religious origins—that they conform to a unified Turkish culture; on the other hand, an equally assimilationist modernization project was designed to achieve cultural recognition from the heart of Europe. By linking historical and contemporary discourses, this article shows how tropes of Jewishness have played—and continue to play—a critical role in the conception of Turkish nationhood. The status of Erich Auerbach, Chair of the Faculty for Western Languages and Literatures at İstanbul University from 1936 to 1947, is central to this investigation into the place of Turkish and German Jews in modern Turkey.

The Duel and the Daïs: Iliadic Warfare as Spectacle

2019 ◽  
pp. 65-108
Author(s):  
Tobias Myers
Keyword(s):  
Critical Role ◽  
The Other ◽  
Mise En Abyme ◽  
Other Hand ◽  
The One ◽  
The Relationship

Chapter 2 explores how the Olympians and the Iliad’s audience are positioned as viewers for the warfare in Books 1–4, and their roles defined. The first section focuses on the gods. Homer initially defines the gods’ role as viewers by drawing on two specific paradigms of live event: entertainment at a daïs (banquet), and the formal duel. Each of these paradigms carries its own suggestions as to the nature of the event, its stakes, and the relationship between viewer and action. As entertainment accompanying a daïs, the warfare may generate pleasure (terpein) for viewers whose critical role is to praise or blame the dramatic figure pulling the strings. As a spectacle modelled on the formal duel, the warfare is observed by implicated, partisan viewers, who are themselves a part of the conflict, and can become actors by entering the central space. Rich tension is generated by the combination of these paradigms. The chapter’s second section reads the opening of Book 4, in which the gods watch a duel from their daïs, as a mise en abyme of the spectacle experience offered by the Iliad to its listeners. On the one hand, the combination of duel and daïs shapes audience understanding of the kind of spectacle that they, too, are witnessing, and their own relationship to the action. On the other hand, the gods’ particular responses—both to the events on the ground and to their staging and direction—dramatize possible responses on the part of Homer’s audience.

scholarly journals On the Other Hand…: Enhancing Promotional Effectiveness with Haptic Cues

2019 ◽  
Vol 57 (1) ◽  
pp. 100-117
Author(s):  
Virginie Maille ◽  
Maureen Morrin ◽  
Ryann Reynolds-McIlnay
Keyword(s):  
Visual Field ◽  
Critical Role ◽  
The Other ◽  
Dominant Hand ◽  
Other Hand ◽  
Perceived Ownership ◽  
The Creation ◽  
Haptic Cues ◽  
Hand Action

People like graspable objects more when the objects are located on the dominant-hand side of their body or when the handles point toward their dominant-hand side. However, many products do not have handles or are not graspable (e.g., services, objects hanging on the wall). Can nongraspable products nevertheless benefit from the effects of appealing to viewers’ dominant hands? The present research shows that, yes, consumers respond more positively to nongraspable products if a haptic cue (an object that is graspable or suggestive of hand action) is located within the same visual field as the target and is positioned to appeal to the viewer’s dominant hand. This result is driven by the creation and transfer of perceived ownership from cue to target. These findings extend the use of haptic cues to nongraspable products and uncover the critical role played by perceived ownership, including its ability to transfer from one object to another located in the same visual field. Moreover, the current research demonstrates situations in which the use of haptic cues will not enhance response.

Nutritional Requirement for 4-Aminobenzoate Caused by Mutation of Dihydropteroate Synthetase

1976 ◽  
Vol 31 (5-6) ◽  
pp. 285-287 ◽  
Author(s):  
Helmut Rappold ◽  
Adelbert Bacher
Keyword(s):  
Parent Strain ◽  
The Other ◽  
Synthetase Activity ◽  
Nutritional Requirement ◽  
Wild Type ◽  
Aerobacter Aerogenes ◽  
Low Level ◽  
Other Hand ◽  
High Concentrations

Abstract Aerobacter aerogenes mutant 62-1 AC requires high concentrations of 4-aminobenzoate for growth. The mutant accumulates N-glucosyl-4-aminobenzoate and has an intact 4-aminobenzoate synthetase (Bacher, Gilch, Rappold, and Lingens, Z. Naturforsch. 28c, 614 - 617 [1973]). On the other hand the ability of the mutant to synthesize dihydropteroate is markedly reduced. The dihydropteroate synthetase level of mutant 62-1 AC is 1% as compared to the parent strain. Spontaneous revertants of mutant 62-1 AC show wild type levels of dihydropteroate synthetase. We conclude that the requirement for 4-aminobenzoate in mutant 62-1 AC is due to poor utilization of 4-aminobenzoate as a consequence of the low level of dihydropteroate synthetase activity.

H-Ras Is Involved in the Inside-out Signaling Pathway of Interleukin-3–Induced Integrin Activation

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1540-1548 ◽  
Author(s):  
Hirohiko Shibayama ◽  
Naoyuki Anzai ◽  
Stephen E. Braun ◽  
Seiji Fukuda ◽  
Charlie Mantel ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Dominant Negative ◽  
The Other ◽  
Wild Type ◽  
Integrin Activation ◽  
Mapk Kinase ◽  
Interleukin 3 ◽  
Other Hand ◽  
Inside Out ◽  
Constitutively Active

Abstract The proto-oncogene product, p21ras, has been implicated in the cellular mechanism of adhesion, although its precise role has been controversial. Numerous cytokines and growth-factors activate Ras, which is an important component of their growth-promoting signaling pathways. On the other hand, the role of Ras in cytokine-induced adhesion has not been elucidated. We therefore investigated the function of H-Ras in the inside-out signaling pathway of interleukin-3 (IL-3)–induced integrin activation in the murine Baf3 cell line after transfection of cells with either constitutively active, dominant-negative, or wild-type H-Ras cDNAs. Adhesion of Baf3 cells to fibronectin was induced by IL-3 in a dose-dependent manner via very late antigen-4 (VLA-4; 4β1 integrins) and VLA-5 (5β1 integrins) activation. On the other hand, IL-4 did not induce the adhesion of Baf3 cells to fibronectin, although IL-4 did stimulate the cell proliferation of Baf3 cells. Constitutively active H-Ras–transfected Baf3 cells adhered to fibronectin without IL-3 stimulation through VLA-4 and VLA-5, whereas dominant-negative H-Ras–transfected Baf3 cells showed significantly less adhesion induced by IL-3 compared with wild-type and constitutively active H-Ras–transfected Baf3 cells. Anti-β1 integrin antibody (clone; 9EG7), which is known to change integrin conformation and activate integrins, induced the adhesion of dominant-negative H-Ras–transfected Baf3 cells as much as the other types of H-Ras–transfected Baf3 cells. 8-Br-cAMP, Dibutyryl-cAMP, Ras-Raf-1 pathway inhibitors, and PD98059, a MAPK kinase inhibitor, suppressed proliferation and phosphorylation of MAPK detected by Western blotting with anti–phospho-MAPK antibody, but not adhesion of any type of H-Ras–transfected Baf3 cells, whereas U-73122, a phospholipase C (PLC) inhibitor, suppressed adhesion of these cells completely. These data indicate that H-Ras and PLC, but not Raf-1, MAPK kinase, or the MAPK pathway, are involved in the inside-out signaling pathway of IL-3–induced VLA-4 and VLA-5 activation in Baf3 cells.

scholarly journals Revisiting the role of PML protein targeting and disruption of PML bodies in human cytomegalovirus infection

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Christina Paulus ◽  
Thomas Harwardt ◽  
Bernadette Walter ◽  
Andrea Marxreiter ◽  
Michael Nevels
Keyword(s):  
Gene Expression ◽  
Viral Replication ◽  
Human Cytomegalovirus ◽  
Critical Role ◽  
Wild Type ◽  
Early Protein ◽  
Type Protein ◽  
Wild Type Protein ◽  
Pml Bodies

Promyelocytic leukaemia (PML) bodies are nuclear organelles implicated in post-translational modification by small ubiquitin-like modifier (SUMO) proteins and in the antiviral host cell response to infection. The 72-kDa immediate-early protein 1 (IE1) is considered the principal antagonist of PML bodies encoded by the human cytomegalovirus, one of eight human herpesviruses. Previous work has suggested that the interaction between IE1 and PML proteins, the central organisers of PML bodies, and the subsequent disruption of these organelles serve a critical role in viral replication by counteracting intrinsic antiviral immunity and the induction of interferon (IFN)-stimulated genes. However, this picture has emerged largely from studying mutant IE1 proteins known or predicted to be globally misfolded und metabolically unstable. We systematically screened for stable IE1 mutants by clustered charge-to-alanine scanning. We identified a mutant protein (IE1cc172-176) selectively defective for PML interaction. Functional comparisons between the mutant and wild-type protein revealed that IE1 can undergo modification by mixed polymeric SUMO chains and that it targets PML and Sp100, the two main constituents of PML bodies, via distinct mechanisms. Unexpectedly, IE1cc172-176 supported viral replication almost as efficiently as wild-type IE1. Moreover, lower instead of higher (as expected) levels of tumor necrosis factor alpha, IFN-beta, IFN-lambda and IFN-stimulated gene expression were observed with the mutant compared to the wild-type protein and virus. These results suggest that the disruption of PML bodies is linked to induction rather than inhibition of antiviral gene expression. Our findings challenge current views regarding the role of PML bodies in viral infection.

Against realism: Hegel and Adorno on philosophy’s critical role

2019 ◽  
Vol 46 (2) ◽  
pp. 183-202
Author(s):  
Bernardo Ferro
Keyword(s):  
Political Change ◽  
Critical Role ◽  
Scientific Discourse ◽  
The Other ◽  
Main Task ◽  
Naive Realism ◽  
Naïve Realism ◽  
Other Hand ◽  
The One

Key representatives of the dialectical tradition, Hegel and Adorno conceived philosophy as a critical tool, directed both at the naive realism of ordinary reason and the more sophisticated realism of modern scientific discourse. For the two authors, philosophy’s main task is to question received ideas and practices and to expose their underlying contradictions, thereby enabling meaningful forms of cultural and political change. But while for Hegel this procedure takes the form of a systematic enquiry, leading from a spurious to a true account of reality, Adorno rejects the idea that reason and reality can be reconciled. On the one hand, he praises Hegel for having developed a truly dialectical form of criticism, set into motion by the immanent unfolding of reality’s intrinsic contradictions. On the other hand, he views Hegel’s emphasis on systematic integration as a form of dogmatism, which must itself be criticized. Instead of a ‘positive’ or ‘closed’ dialectic, fuelled by the expectation of a final overarching synthesis, Adorno calls for a ‘negative’ or ‘open’ dialectic, radically averse to all forms of unification. In doing so, however, he is led to question the very limits of conceptual reason, leaving criticism vulnerable to new forms of attack.

Abstract 16603: Appropriate Timing of Pacemaker Implantation in Patients With Wild-Type and Variant Amyloidogenic Transthyretin Cardiac Amyloidosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yusei Kawahara ◽  
Miwa Ito ◽  
Tadashi Hoshiyama ◽  
Hisanori Kanazawa ◽  
Kenichi Tsujita
Keyword(s):  
Cardiac Amyloidosis ◽  
Pacemaker Implantation ◽  
The Other ◽  
Cardiac Conduction ◽  
Wild Type ◽  
Conduction Disorders ◽  
Other Hand ◽  
Conduction Disorder ◽  
Second Degree

Background and Objectives: It has been shown that cardiac conduction disorders can be seen in patients with wild-type amyloidogenic transthyretin (ATTRwt) and variant ATTR (ATTRv) cardiac amyloidosis. However, its appropriate timing of pacemaker implantation has not been clarified yet. Methods and Results: The consecutive 100 patients with ATTRwt cardiac amyloidosis who diagnosed by myocardium biopsy and/or technetium-99m-pyrophosphate scintigraphy and 62 patients with ATTRv cardiac amyloidosis who diagnosed by means of genetic screening were included in this study. In patients with ATTRwt cardiac amyloidosis, 21 patients have normal conduction at the time of diagnosis. However, conduction disorder had seen in only 5 patient (first degree atrioventricular block (AVB); 4 patients, complete AVB; 1 patients) and only one patient underwent cardiac implantable electric device (CIED) implantation during follow-up period. On the other hand, in patients with ATTRv cardiac amyloidosis, 36 patients have normal conduction at the time of diagnosis. However, conduction disorder had seen in 13 patient (first degree AVB; 8 patients, second degree AVB; 3 patients, trifascicular block; 1 patients, complete AVB; 1 patients) (5/21 vs 13/36, p=0.335) and 6 patients underwent CIED implantation during follow-up period (1/21 vs 6/36, p=0.186). Furthermore, in ATTRwt cardiac amyloidosis, 10 patients (first degree AVB; 2 patients, second degree AVB; 1 patient, trifascicular block; 7 patients) had underwent CIED implantation because of cardiac conduction disorders and/or prevention of sudden cardiac death. However, only 4 patients with trifascicular block progressed to complete AVB.On the other hand, In ATTRv cardiac amyloidosis, 14 patients (first degree AVB; 2 patients, second degree AVB; 4 patient, trifascicular block; 8 patients) had underwent CIED implantation for same reason. However, only 3 patients with trifascicular block progressed to complete AVB. Conclusions: Patients with ATTRv cardiac amyloidosis were more likely to progress conduction disorders than those with ATTRwt cardiac amyloidosis. However, prophylactic pacemaker implantation might had not need in both ATTRwt and ATTRv patients with first or second degree AVB.

Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice

2019 ◽  
Vol 32 (3) ◽  
pp. 213-219 ◽  
Author(s):  
Yu-Hsien Lin ◽  
Satoko Tahara-Hanaoka ◽  
Kei Nagai ◽  
Soichiro Yoshikawa ◽  
Masato Kubo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Food Allergy ◽  
Critical Role ◽  
The Other ◽  
Wild Type ◽  
Selective Suppression ◽  
Severe Hypothermia ◽  
Human And Mouse ◽  
Lethal Hypothermia

Abstract Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcεRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1−/−) mice developed more severe hypothermia, a higher mortality rate and a greater incidence of diarrhea than did wild-type (WT) mice in an oral ovalbumin (OVA)-induced food allergy model. MC-deficient Mas–TRECK mice, which had been reconstituted with either WT or Milr1−/− bone marrow-derived cultured MCs, did not develop hypothermia in this food allergy model. On the other hand, depletion of basophils by injection of anti-CD200R3 antibody rescued Milr1−/− mice from lethal hypothermia but not from diarrhea. In vitro analyses demonstrated that Allergin-1 inhibits IgE-dependent activation of both human and mouse basophils. Thus, Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis.

Mutagenesis-induced conformational change in domain B of a pullulan-hydrolyzing α-amylase TVA I

Amylase ◽  
2018 ◽  
Vol 2 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Takashi Tonozuka ◽  
Takanori Nihira ◽  
Masahiro Mizuno ◽  
Atsushi Nishikawa ◽  
Shigehiro Kamitori
Keyword(s):  
Kinetic Analysis ◽  
Crystal Structures ◽  
Conformational Change ◽  
The Other ◽  
Wild Type ◽  
Other Hand ◽  
Thermoactinomyces Vulgaris ◽  
Catalytic Cleft

Abstract An α-amylase from Thermoactinomyces vulgaris, TVA I, hydrolyzes both α-1,4- and α-1,6-glucosidic linkages. Two variants of TVA I have been previously constructed, one containing a substitution of three residues, Ala357- Gln359-Tyr360, with Val-Asn-Glu (AQY/VNE), and the other bearing a deletion of 11 residues from Ala363 to Asn373 (Del11). The activities of both AQY/VNE and Del11 for the α-1,4-glucosidic linkage of maltotriose were decreased compared to that of wild-type TVA I, while the activities of the two variants for the α-1,6-glucosidic linkage of a trisaccharide, isopanose, were less significantly altered. Here, we determined the crystal structures of AQY/VNE and Del11. The structure of AQY/VNE was almost isomorphous with that of wild-type TVA I. On the other hand, the structure of Del11 showed that a conformational change in domain B was induced by the 11-residue deletion, causing narrowing of the catalytic cleft. Taken together with the results of kinetic analysis, this narrower catalytic cleft is likely responsible for the preference of the TVA I enzyme for the α-1,6-glucosidic linkage.

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