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1.
PLoS One ; 18(12): e0295229, 2023.
Article in English | MEDLINE | ID: mdl-38051751

ABSTRACT

Many workers are experiencing the downsides of being exposed to an overload of information and communication technology (ICT), highlighting the need for resources to cope with the resulting technostress. This article offers a novel cross-level perspective on technostress by examining how the context of the welfare state influences the relationship between income and technostress. Showing that individuals with higher income experience less technostress, this study argues that the welfare state represents an additional coping resource, in particular in the form of unemployment benefits. Since unemployment benefits insure income earners in the case of job loss, the negative effect of income on technostress should increase with higher levels of unemployment generosity. In line with these expectations, empirical results based on original survey data collected in collaboration with the OECD show that the impact of income on technostress varies across welfare state contexts. Implications for public health and policymakers are being discussed.


Subject(s)
Digital Technology , Income , Information Technology , Organisation for Economic Co-Operation and Development , Stress, Psychological , Unemployment , Humans , Communication , Organisation for Economic Co-Operation and Development/economics , Socioeconomic Factors , Unemployment/psychology , Stress, Psychological/economics , Stress, Psychological/prevention & control , Stress, Psychological/psychology , Coping Skills/economics , Occupational Stress/economics , Occupational Stress/prevention & control , Occupational Stress/psychology
2.
Curr Cardiol Rep ; 25(10): 1233-1246, 2023 10.
Article in English | MEDLINE | ID: mdl-37851270

ABSTRACT

PURPOSE OF REVIEW: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause myocardial ischemia and adverse cardiac events. The presence of AAOCA anatomy itself does not necessarily implicate a need for revascularization. Therefore, the purpose of this review is to assess how noninvasive comprehensive anatomic- and physiologic evaluation may guide patient management. RECENT FINDINGS: The assessment of AAOCA includes an accurate description of the anomalous origin/vessel course including anatomical high-risk features such as a slit-like ostium, proximal narrowing, elliptic vessel shape, acute take-off angle, intramural course, and possible concomitant coronary atherosclerosis and hemodynamics. Various cardiac imaging modalities offer unique advantages and capabilities in visualizing these anatomical and functional aspects of AAOCA. This review explored the role of noninvasive multimodality imaging in the characterization of AAOCA by highlighting the strengths, limitations, and potential applications of the current different cardiac imaging methods, with a focus on the pathophysiology of myocardial ischemia and stress testing protocols.


Subject(s)
Coronary Artery Disease , Coronary Vessel Anomalies , Myocardial Ischemia , Humans , Coronary Vessels/diagnostic imaging , Coronary Vessel Anomalies/diagnostic imaging , Aorta , Tomography, X-Ray Computed , Myocardial Ischemia/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/complications
3.
Langmuir ; 39(12): 4207-4215, 2023 Mar 28.
Article in English | MEDLINE | ID: mdl-36919825

ABSTRACT

Emulsions often act as carriers for water-insoluble solutes that are delivered to a specific target. The molecular transport of solutes in emulsions can be facilitated by surfactants and is often limited by diffusion through the continuous phase. We here investigate this transport on a molecular scale by using a lipophilic molecular rotor as a proxy for solutes. Using fluorescence lifetime microscopy we track the transport of these molecules from the continuous phase toward the dispersed phase in polydisperse oil-in-water emulsions. We show that this transport comprises two time scales, which vary significantly with droplet size and surfactant concentration, and, depending on the type of surfactant used, can be limited either by transport across the oil-water interface or by diffusion through the continuous phase. By studying the time-resolved fluorescence of the fluorophore, accompanied by molecular dynamics simulations, we demonstrate how the rate of transport observed on a macroscopic scale can be explained in terms of the local environment that the probe molecules are exposed to.

4.
mBio ; 14(1): e0192121, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36715508

ABSTRACT

Viruses are the most abundant biological entities in the ocean and show great diversity in terms of size, host specificity, and infection cycle. Lytic viruses induce host cell lysis to release their progeny and thereby redirect nutrients from higher to lower trophic levels. Studies continue to show that marine viruses can be ingested by nonhost organisms. However, not much is known about the role of viral particles as a nutrient source and whether they possess a nutritional value to the grazing organisms. This review seeks to assess the elemental composition and biogeochemical relevance of marine viruses, including roseophages, which are a highly abundant group of bacteriophages in the marine environment. We place a particular emphasis on the phylum Nucleocytoviricota (NCV) (formerly known as nucleocytoplasmic large DNA viruses [NCLDVs]), which comprises some of the largest viral particles in the marine plankton that are well in the size range of prey for marine grazers. Many NCVs contain lipid membranes in their capsid that are rich carbon and energy sources, which further increases their nutritional value. Marine viruses may thus be an important nutritional component of the marine plankton, which can be reintegrated into the classical food web by nonhost organism grazing, a process that we coin the "viral sweep." Possibilities for future research to resolve this process are highlighted and discussed in light of current technological advancements.


Subject(s)
Bacteriophages , Viruses , Seawater , Viruses/genetics , Viruses/metabolism , Bacteriophages/genetics , Plankton , Virion
5.
JACC Case Rep ; 4(15): 929-933, 2022 Aug 03.
Article in English | MEDLINE | ID: mdl-35935159

ABSTRACT

We present the management of an anomalous coronary artery originating from the opposite sinus of Valsalva with comprehensive diagnostic workup including noninvasive coronary computed tomography (CT) derived fractional flow reserve (FFR) and invasive dobutamine-volume challenge-FFR/intravascular ultrasound. After surgical operation, treatment success was quantified by anatomical and functional analysis in postoperative CT. (Level of Difficulty: Advanced.).

6.
J Chem Phys ; 156(20): 201101, 2022 May 28.
Article in English | MEDLINE | ID: mdl-35649835

ABSTRACT

Viscosity is a key property of liquids, but it is difficult to measure in short-lived, metastable samples due to the long measuring times required by conventional rheology. Here, we show how this problem can be solved by using fluorescent molecular rotors. The excited-state fluorescence decay rate of these molecules is sensitive to the viscosity of their local environment, and by combining pulsed laser excitation with time-resolved fluorescence detection, we can measure viscosities with a time resolution of a few ns. We demonstrate this by measuring in real time the viscosity change in glycerol induced by a nanosecond temperature jump. This new approach makes it possible to measure the viscosity of extremely short-lived states of matter.

7.
Front Cardiovasc Med ; 9: 800720, 2022.
Article in English | MEDLINE | ID: mdl-35282374

ABSTRACT

Introduction: In patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction. Methods: A group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain. Results: In healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (-5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone. Conclusion: In myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.

8.
Am J Cardiol ; 168: 151-158, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35065801

ABSTRACT

The prevalence and implications of radial artery occlusion (RAO) after transradial catheterization are an intensely discussed topic, resulting in numerous preventive strategies such as adjusted anticoagulation, residual-patency hemostasis, or distal puncture site. The present study aimed at assessing an association of palmar arch, in particular radial artery collateral function and RAO after transradial access (TRA) catheterization. Radial artery collateral function was determined using radial artery pressure signals in the nonobstructed vessel and during brief manual occlusion of the more proximal radial artery. Collateral flow index, the ratio of mean occlusive divided by mean nonocclusive arterial blood pressure, both subtracted by central venous pressure, was determined during manual RAO (radial artery collateral flow index [CFIrad]). The presence or absence of RAO was determined by Doppler ultrasound at least 3 months after TRA. A total of 630 patients with TRA coronary angiography underwent palmar arch, that is, radial and radial plus ulnar artery collateral function assessment. CFIrad was equal to 0.808 ± 0.144 (95% confidence interval 0.797 to 0.819). A total of 200 patients underwent Doppler ultrasound examination of their forearm arterial circulation 301 ± 140 days after TRA. Eight (4%) patients showed signs of RAO, 4 of whom (2%) had a complete RAO and 4 (2%) a stenosis above 30%. Patients with RAO showed a higher CFIrad than those without RAO: 0.900 ± 0.074 versus 0.801 ± 0.154 (p = 0.006). In conclusion, complete RAO as determined by Doppler ultrasound later than 3 months after TRA is rare (2%). In the long run, RAO appears to be related to a very well-developed radial artery collateral function.


Subject(s)
Arterial Occlusive Diseases , Radial Artery , Arterial Occlusive Diseases/diagnosis , Arterial Occlusive Diseases/epidemiology , Arterial Occlusive Diseases/etiology , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Coronary Angiography/methods , Hand , Humans , Punctures
9.
Biol Rev Camb Philos Soc ; 97(1): 179-194, 2022 02.
Article in English | MEDLINE | ID: mdl-34514703

ABSTRACT

Collectively known as phytoplankton, photosynthetic microbes form the base of the marine food web, and account for up to half of the primary production on Earth. Haptophytes are key components of this phytoplankton community, playing important roles both as primary producers and as mixotrophs that graze on bacteria and protists. Viruses influence the ecology and diversity of phytoplankton in the ocean, with the majority of microalgae-virus interactions described as 'boom and bust' dynamics, which are characteristic of acute virus-host systems. Most haptophytes are, however, part of highly diverse communities and occur at low densities, decreasing their chance of being infected by viruses with high host specificity. Viruses infecting these microalgae have been isolated in the laboratory, and there are several characteristics that distinguish them from acute viruses infecting bloom-forming haptophytes. Herein we synthesise what is known of viruses infecting haptophyte hosts in the ocean, discuss the adaptive evolution of haptophyte-infecting viruses -from those that cause acute infections to those that stably coexist with their host - and identify traits of importance for successful survival in the ocean.


Subject(s)
Haptophyta , Microalgae , Phycodnaviridae , Viruses , Phycodnaviridae/genetics , Phytoplankton
10.
Eur Respir J ; 59(4)2022 04.
Article in English | MEDLINE | ID: mdl-34446463

ABSTRACT

BACKGROUND: Successful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury. METHODS: LPS was intranasally injected into wild-type and transgenic mice. Gain and loss of VEGF-C/VEGFR-3 signalling function experiments employed adenovirus-mediated intranasal delivery of VEGF-C (Ad-VEGF-C vector) and soluble VEGFR-3 (sVEGFR-3) or anti-VEGFR-3 blocking antibodies and mice with a deletion of VEGFR-3 in myeloid cells. RESULTS: The early phase of lung injury was significantly alleviated by the overexpression of VEGF-C with increased levels of bronchoalveolar lavage (BAL) fluid interleukin-10 (IL-10), but worsened in the later phase by VEGFR-3 inhibition upon administration of Ad-sVEGFR-3 vector. Injection of anti-VEGFR-3 antibodies to mice in the resolution phase inhibited recovery from lung injury. The VEGFR-3-deleted mice had a shorter survival time than littermates and more severe lung injury in the resolution phase. Alveolar macrophages in the resolution phase digested most of the extrinsic apoptotic neutrophils and VEGF-C/VEGFR-3 signalling increased efferocytosis via upregulation of integrin αv in the macrophages. We also found that incubation with BAL fluid from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreased VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages. CONCLUSIONS: VEGF-C/VEGFR-3 signalling in macrophages ameliorates experimental lung injury. This mechanism may also provide an explanation for ARDS resolution.


Subject(s)
Acute Lung Injury , Respiratory Distress Syndrome , Acute Lung Injury/metabolism , Animals , Humans , Interleukin-10/adverse effects , Interleukin-10/metabolism , Lipopolysaccharides , Macrophages, Alveolar/metabolism , Mice , Mice, Inbred C57BL , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor C/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism
11.
J Eur Soc Policy ; 32(4): 393-406, 2022 Oct.
Article in English | MEDLINE | ID: mdl-38603158

ABSTRACT

The COVID-19 pandemic represents an enormous challenge for healthcare systems around the globe. Using original panel survey data for the case of Germany, this article studies how specific trust in the healthcare system to cope with this crisis has evolved during the course of the pandemic and whether this specific form of trust is associated with general political trust. The article finds strong evidence for a positive and robust association between generalized political trust and performance perceptions regarding the efficiency and fairness of the crisis response as well as individual treatment conditions. The article also shows that specific trust in healthcare remained relatively stable throughout 2020, but declined significantly in the spring of 2021.

12.
Soft Matter ; 17(27): 6536-6541, 2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34259707

ABSTRACT

Deposits from evaporating drops have been shown to take a variety of shapes, depending on the physicochemical properties of both solute and solvent. Classically, the evaporation of drops of colloidal suspensions leads to the so-called coffee ring effect, caused by radially outward flows. Here we investigate deposits from evaporating drops containing living motile microalgae (Chlamydomonas reinhardtii), which are capable of resisting these flows. We show that utilizing their light-sensitivity allows control of the final pattern: adjusting the wavelength and incident angle of the light source enables forcing the formation, completely suppressing and even directing the spatial structure of algal coffee rings.


Subject(s)
Microalgae , Solutions
13.
ISME J ; 15(12): 3714-3721, 2021 12.
Article in English | MEDLINE | ID: mdl-34083751

ABSTRACT

Extracellular vesicles are produced by organisms from all kingdoms and serve a myriad of functions, many of which involve cell-cell signaling, especially during stress conditions and host-pathogen interactions. In the marine environment, communication between microorganisms can shape trophic level interactions and population succession, yet we know very little about the involvement of vesicles in these processes. In a previous study, we showed that vesicles produced during viral infection by the ecologically important model alga Emiliania huxleyi, could act as a pro-viral signal, by expediting infection and enhancing the half-life of the virus in the extracellular milieu. Here, we expand our laboratory findings and show the effect of vesicles on natural populations of E. huxleyi in a mesocosm setting. We profile the small-RNA (sRNA) cargo of vesicles that were produced by E. huxleyi during bloom succession, and show that vesicles applied to natural assemblages expedite viral infection and prolong the half-life of this major mortality agent of E. huxleyi. We subsequently reveal that exposure of the natural assemblage to E. huxleyi-derived vesicles modulates not only host-virus dynamics, but also other components of the microbial food webs, thus emphasizing the importance of extracellular vesicles to microbial interactions in the marine environment.


Subject(s)
Extracellular Vesicles , Haptophyta , DNA Viruses , Eutrophication , Host Microbial Interactions , Host-Pathogen Interactions
14.
J Phys Chem Lett ; 12(12): 3182-3186, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33759527

ABSTRACT

The macroscopic viscosity of polymer solutions in general differs strongly from the viscosity at the nanometer scale, and the relation between the two can be complicated. To investigate this relation, we use a fluorescent molecular rotor that probes the local viscosity of its molecular environment. For a range of chain lengths and concentrations, the dependence of the fluorescence on the macroscopic viscosity is well described by the classical Förster-Hoffmann (FH) equation, but the value of the FH exponent depends on the polymer chain length. We show that all data can be collapsed onto a master curve by plotting the fluorescence versus polymer concentration, which we explain in terms of the characteristic mesh size of the polymer solution. Using known scaling laws for polymers then allows us to quantitatively explain the relation between the FH exponent and the polymer chain length, allowing us to link the nano- to the macroviscosity.

15.
Angew Chem Int Ed Engl ; 60(14): 7540-7546, 2021 Mar 29.
Article in English | MEDLINE | ID: mdl-33416197

ABSTRACT

Here we show that by adjusting the concentration of tetrabutyl ammonium and phosphonium salts in water (≈1.5-2.0 m), hydrophobic solvation triggers the formation of a unique, highly incompressible supramolecular liquid, with a dynamic structure similar to clathrates, involving essentially all H2 O molecules of the solvent. Despite the increasing local order, the thermal diffusivity, and compressibility of these supramolecular liquids is strongly decreased with respect to bulk water due to slower relaxation dynamics. The results presented in this paper open an avenue to design a new family of supramolecular fluids, stable under atmospheric conditions, which can find important technological applications in energy storage and conversion.

16.
Nucleic Acids Res ; 49(6): 3461-3489, 2021 04 06.
Article in English | MEDLINE | ID: mdl-33398329

ABSTRACT

LARP1 is a key repressor of TOP mRNA translation. It binds the m7Gppp cap moiety and the adjacent 5'TOP motif of TOP mRNAs, thus impeding the assembly of the eIF4F complex on these transcripts. mTORC1 controls TOP mRNA translation via LARP1, but the details of the mechanism are unclear. Herein we elucidate the mechanism by which mTORC1 controls LARP1's translation repression activity. We demonstrate that mTORC1 phosphorylates LARP1 in vitro and in vivo, activities that are efficiently inhibited by rapamycin and torin1. We uncover 26 rapamycin-sensitive phospho-serine and -threonine residues on LARP1 that are distributed in 7 clusters. Our data show that phosphorylation of a cluster of residues located proximally to the m7Gppp cap-binding DM15 region is particularly sensitive to rapamycin and regulates both the RNA-binding and the translation inhibitory activities of LARP1. Our results unravel a new model of translation control in which the La module (LaMod) and DM15 region of LARP1, both of which can directly interact with TOP mRNA, are differentially regulated: the LaMod remains constitutively bound to PABP (irrespective of the activation status of mTORC1), while the C-terminal DM15 'pendular hook' engages the TOP mRNA 5'-end to repress translation, but only in conditions of mTORC1 inhibition.


Subject(s)
Autoantigens/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Protein Biosynthesis , Ribonucleoproteins/metabolism , Amino Acid Motifs , Autoantigens/chemistry , HEK293 Cells , Humans , Naphthyridines/pharmacology , Phosphorylation/drug effects , Protein Binding , Ribonucleoproteins/chemistry , Serine/metabolism , Sirolimus/pharmacology , Threonine/metabolism , Tyrosine/metabolism , SS-B Antigen
17.
Phys Chem Chem Phys ; 22(36): 20524-20530, 2020 Sep 23.
Article in English | MEDLINE | ID: mdl-32966417

ABSTRACT

Self-assembled ionic liquid crystals are anisotropic ionic conductors, with potential applications in areas as important as solar cells, battery electrolytes and catalysis. However, many of these applications are still limited by the lack of precise control over the variety of phases that can be formed (nematic, smectic, or semi/fully crystalline), determined by a complex pattern of different intermolecular interactions. Here we report the results of a systematic study of crystallization of several imidazolium salts in which the relative contribution of isotropic coulombic and directional H-bond interactions is carefully tuned. Our results demonstrate that the relative strength of directional H-bonds with respect to the isotropic Coulomb interaction determines the formation of a crystalline, semi-crystalline or glassy phase at low temperature. The possibility of pinpointing H-bonding directionality in ionic liquids make them model systems to study the crystallization of an ionic solid under a perturbed Coulomb potential.

18.
Am Heart J ; 230: 1-12, 2020 12.
Article in English | MEDLINE | ID: mdl-32949505

ABSTRACT

Natural, nonsurgical internal mammary artery (IMA) bypasses to the coronary circulation have been shown to function as extracardiac sources of myocardial blood supply. The goal of this randomized, placebo-controlled, double-blind trial was to test the efficacy of permanent right IMA (RIMA) device occlusion on right coronary artery (RCA) occlusive blood supply and on clinical and electrocardiographic (ECG) signs of myocardial ischemia. METHODS: This was a prospective superiority trial in 100 patients with chronic coronary artery disease randomly allocated (1:1) to RIMA vascular device occlusion (verum group) or to RIMA sham procedure (placebo group). The primary study end point was RCA collateral flow index (CFI) as obtained during a 1-minute ostial RCA balloon occlusion at baseline before and at follow-up examination 6 weeks after the trial intervention. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. Simultaneously obtained secondary study end points were the registration of angina pectoris and quantitative intracoronary ECG ST-segment shift. RESULTS: CFI change during the follow-up period was +0.036 ±â€¯0.068 in the verum group and -0.021 ±â€¯0.097 in the placebo group (P = .0011). Angina pectoris during the same RCA balloon occlusions had disappeared at follow-up in 14/49 patients of the verum group and in 4/49 patients of the placebo group (P = .0091). Simultaneous intracoronary ECG ST-segment shift change revealed diminished myocardial ischemia at follow-up in the verum group and more severe ischemia in the placebo group. CONCLUSIONS: Permanent RIMA device occlusion augments RCA supply to the effect of diminishing clinical and electrocardiographic signs of myocardial ischemia during a brief controlled coronary occlusion.


Subject(s)
Balloon Occlusion/methods , Collateral Circulation , Coronary Artery Disease/therapy , Coronary Vessels/physiology , Mammary Arteries , Myocardial Ischemia/diagnosis , Aged , Angina Pectoris/physiopathology , Angina Pectoris/therapy , Blood Pressure , Cardiac Catheterization/methods , Chronic Disease , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/physiopathology , Coronary Circulation , Double-Blind Method , Electrocardiography , Equivalence Trials as Topic , Female , Humans , Male , Mammary Arteries/diagnostic imaging , Myocardial Ischemia/physiopathology , Placebos/therapeutic use , Prospective Studies
20.
Elife ; 62017 04 07.
Article in English | MEDLINE | ID: mdl-28379136

ABSTRACT

The 5'terminal oligopyrimidine (5'TOP) motif is a cis-regulatory RNA element located immediately downstream of the 7-methylguanosine [m7G] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, a cap analog (m7GTP), and a capped cytidine (m7GpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5'TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5'TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis.


Subject(s)
Autoantigens/chemistry , Autoantigens/metabolism , Eukaryotic Initiation Factor-4E/antagonists & inhibitors , Eukaryotic Initiation Factor-4F/antagonists & inhibitors , RNA 5' Terminal Oligopyrimidine Sequence , RNA, Messenger/metabolism , Ribonucleoproteins/chemistry , Ribonucleoproteins/metabolism , Chromatin Immunoprecipitation , Crystallography, X-Ray , Gene Expression Regulation , Models, Molecular , Protein Binding , Protein Biosynthesis , Protein Conformation , RNA Stability , SS-B Antigen
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