scholarly journals Dual RNA modulation of protein mobility and stability within phase-separated condensates

2021 ◽  
Author(s):  
Andrés R. Tejedor ◽  
Adiran Garaizar ◽  
Jorge Ramírez ◽  
Jorge R. Espinosa
Keyword(s):  
Phase Separation ◽  
Coarse Grained ◽  
High Concentration ◽  
Protein Mobility ◽  
Rna Recognition Motifs ◽  
Self Diffusion ◽  
Age Related ◽  
Recognition Motifs ◽  
The Impact ◽  
Rna Concentration

One of the key mechanisms employed by cells to control their spatiotemporal organization is the formation and dissolution of phase-separated condensates. Such balance between condensate assembly and disassembly can be critically regulated by the presence of RNA. In this work, we use a novel chemically accurate coarse-grained model for proteins and RNA to unravel the impact of poly-uridine RNA in modulating the protein mobility and stability within different biomolecular condensates. We explore the behavior of FUS, hnRNPA1 and TDP-43 proteins along with that of their corresponding prion-like domains and RNA-recognition motifs, from absence to moderately high RNA concentration. By characterising the phase diagram, key molecular interactions, surface tension and viscoelastic properties, we report a dual RNA-induced behavior: On the one hand, poly-uridine enhances phase separation at low concentration, whilst at high concentration, it inhibits the ability of proteins to self-assemble. On the other hand, as a consequence of such stability modulation, the viscoelastic liquid properties of the condensates are significantly enhanced at moderately high RNA concentration, as long as the length of poly-uridine strands is comparable or moderately shorter than those of the proteins, whereas protein self-diffusion barely depends on poly-uridine length. On the whole, our work elucidates the different routes by which RNA can regulate phase separation and condensate dynamics, as well as the subsequent aberrant rigidification implicated in the emergence of various neuropathologies and age-related diseases.

Chemical Composition and Metal Speciation in Porewaters from the Upper Qu’Appelle River Basin, Saskatchewan

1993 ◽  
Vol 28 (1) ◽  
pp. 83-110 ◽  
Author(s):  
Richard E. Farrell ◽  
Jae E. Yang ◽  
P. Ming Huang ◽  
Wen K. Liaw
Keyword(s):  
Amino Acids ◽  
Trace Metal ◽  
River Basin ◽  
Drainage Basin ◽  
Metal Speciation ◽  
Anthropogenic Activities ◽  
High Concentration ◽  
Metal Concentrations ◽  
Carbonate Equilibria ◽  
The Impact

Abstract Porewater samples from the upper Qu’Appelle River basin in Saskatchewan, Canada, were analyzed to obtain metal, inorganic ligand and amino add profiles. These data were used to compute the aqueous speciation of the metals in each porewater using the computer program GEOCHEM-PC. The porewaters were classified as slightly to moderately saline. Metal concentrations reflected both the geology of the drainage basin and the impact of anthropogenic activities. Whereas K and Na were present almost entirely as the free aquo ions, carbonate equilibria dominated the speciation of Ca. Mg and Mn (the predominant metal ligand species were of the type MCO3 (s). MCO30. and MHCO3+). Trace metal concentrations were generally within the ranges reported for non-polluted freshwater systems. Whereas the speciation of the trace metals Cr(III) and Co(II) was dominated by carbonate equilibria, Hg(II)-, Zn(II)- and Fe(II)-speciation was dominated by hydroxy-metal complexes of the type M(OH)+ and M(OH)2°. The speciation of Fe(III) was dominated by Fe(OH)3 (s). In porewaters with high chloride concentrations (> 2 mM), however, significant amounts of Hg(II) were bound as HgCl20 and HgClOH0. The aqueous speciation of Al was dominated by Al(OH)4− and Al2Si2O4(OH)6 (s). Total concentrations of dissolved free amino acids varied from 15.21 to 25.17 umole L−1. The most important metal scavenging amino acids were histidine (due to high stability constants for the metal-histidine complexes) and tryptophan (due to its relatively high concentration in the porewaters. i.e., 5.96 to 7.73 umole L−1). Secondary concentrations of various trace metal-amino add complexes were computed for all the porewaters, but metal-amino acid complexes dominated the speciation of Cu(II) in all the porewaters and Ni(II) in two of the porewaters.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

scholarly journals The impact of vascular risk factors on the thickness and volume of the choroid in AMD patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elżbieta Krytkowska ◽  
Aleksandra Grabowicz ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Zofia Ulańczyk ◽  
Krzysztof Safranow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Risk Factors ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Vascular Risk ◽  
Average Volume ◽  
Central Ring ◽  
Age Related ◽  
The Impact ◽  
Wet Amd

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β =  + 0.18, p = 0.0007, β =  + 0.18, p = 0.0008, respectively) and to dry AMD (β =  + 0.17, p = 0.00003 for both ATC and AVC and β =  − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs =  − 0.13, p < 0.05; Rs =  − 0.12; p < 0.05, Rs =  − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs =  − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.

scholarly journals Postharvest Burning of Crop Residues in Home Stoves in a Rural Site of Daejeon, Korea: Its Impact to Atmospheric Carbonaceous Aerosol

Atmosphere ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 257
Author(s):  
Jin Sang Jung ◽  
Ji Hwan Kang
Keyword(s):  
Urban Area ◽  
Rural Area ◽  
Crop Residues ◽  
Sampling Period ◽  
Carbonaceous Aerosol ◽  
Rural Site ◽  
Carbonaceous Aerosols ◽  
High Concentration ◽  
Crop Residue Burning ◽  
The Impact

To investigate the impact of burning postharvest crop residues in home stoves, PM2.5 samples (particulate matter with a diameter of <2.5 μm) were collected every 3 h at a rural site in Daejeon, Korea during the postharvest season in 2014. A high concentration of levoglucosan was observed with a peak value of 3.8 µg/m3 during the sampling period. The average mannosan/levoglucosan ratio (0.18) at the rural site during a severe BB episode (levoglucosan > 1 μg/m3) was similar to burnings of pepper stems (0.19) and bean stems (0.18) whereas the average OC/levoglucosan ratio (9.9) was similar to burning of pepper stems (10.0), implying that the severe BB episode was mainly attributed to burning of pepper stems. A very strong correlation was observed between levoglucosan and organic carbon (OC) (R2 = 0.81) during the entire sampling period, suggesting that the emission of organic aerosols at the rural site was strongly associated with the burning of crop residues in home stoves. The average mannosan/levoglucosan ratio (0.17 ± 0.06) in the rural area was similar to that in a nearby urban area in Daejeon (0.16 ± 0.04). It was concluded that crop residue burning in a home stove for space heating is one of the important sources of carbonaceous aerosols not only in a rural area but also in the urban area of Daejeon, Korea during the postharvest season.

Impact of Cochlear Implantation on Neurocognitive Subdomains in Adult Cochlear Implant Recipients

2021 ◽  
pp. 1-10
Author(s):  
Christiane Völter ◽  
Lisa Götze ◽  
Imme Haubitz ◽  
Janine Müther ◽  
Stefan Dazert ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implant ◽  
Cochlear Implantation ◽  
Verbal Fluency ◽  
Homogeneous Population ◽  
Delayed Recall ◽  
Hearing Status ◽  
Age Related ◽  
Significant Difference ◽  
The Impact

<b><i>Introduction:</i></b> Age-related hearing loss affects about one-third of the population worldwide. Studies suggest that hearing loss may be linked to cognitive decline and auditory rehabilitation may improve cognitive functions. So far, the data are limited, and the underlying mechanisms are not fully understood. The study aimed to analyze the impact of cochlear implantation on cognition in a large homogeneous population of hearing-impaired adults using a comprehensive non-auditory cognitive assessment with regard to normal-hearing (NH) subjects. <b><i>Material and Methods:</i></b> Seventy-one cochlear implant (CI) candidates with a postlingual, bilateral severe or profound hearing loss aged 66.3 years (standard deviation [SD] 9.2) and 105 NH subjects aged 65.96 years (SD 9.4) were enrolled. The computer-based neurocognitive tool applied included 11 subtests covering attention (M3), short- and long-term memory (recall and delayed recall), working memory (0- and 2-back, Operation Span [OSPAN] task), processing speed (Trail Making Test [TMT] A), mental flexibility (TMT B), inhibition (cFlanker and iFlanker), and verbal fluency. CI patients underwent a neurocognitive testing preoperatively as well as 12 months postoperatively. Impact of hearing status, age, gender, and education on cognitive subdomains was studied. Additionally, after controlling for education and age, cognitive performance of CI subjects (<i>n</i> = 41) was compared to that of NH (<i>n</i> = 34). <b><i>Results:</i></b> CI users achieved significantly better neurocognitive scores 12 months after cochlear implantation than before in most subtests (M3, [delayed] recall, 2-back, OSPAN, iFlanker, and verbal fluency; all <i>p</i> &#x3c; 0.05) except for the TMT A and B. A significant correlation could be found between the postoperative improvement in speech perception and in the attentional task M3 (<i>p</i> = 0.01). Hearing status (<i>p</i> = 0.0006) had the strongest effect on attention, whereas education had a high impact on recall (<i>p</i> = 0.002), OSPAN (<i>p</i> = 0.0004), and TMT A (<i>p</i> = 0.005) and B (<i>p</i> = 0.003). Inhibition was mainly age-dependent with better results in younger subjects (<i>p</i> = 0.016). Verbal fluency was predicted by gender as females outperformed men (<i>p</i> = 0.009). Even after controlling for age and education NH subjects showed a significantly better performance than CI candidates in the recall (<i>p</i> = 0.03) and delayed recall (<i>p</i> = 0.01) tasks. Postoperatively, there was no significant difference between the 2 groups anymore. <b><i>Conclusion:</i></b> Impact of cochlear implantation on neurocognitive functions differs according to the cognitive subdomains. Postoperatively, CI recipients performed as good as age- and education-matched NH subjects.

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