Erratum: Large-scale kinetic roughening behavior of coffee-ring fronts [Phys. Rev. E 106, 044801 (2022)].

This corrects the article DOI: 10.1103/PhysRevE.106.044801.

Senescence and fibrosis in salivary gland aging and disease.

Salivary gland hypofunction is highly prevalent in aged and diseased individuals leading to significant discomfort and morbidity. One factor that contributes to salivary gland hypofunction is cellular aging, or senescence. Senescent cells can impair gland function by secreting paracrine-acting growth factors and cytokines, known as senescence-associated secretory phenotype (SASP) factors. These SASP factors stimulate inflammation, propagate the senescent phenotype through the bystander effect, and stimulate fibrosis. As senotherapeutics that target senescent cells have shown effectiveness in limiting disease manifestations in other conditions, there is interest in the use of these drugs to treat salivary gland hypofunction. In this review, we highlight the contribution of senescence and fibrosis to salivary gland pathologies. We also discuss therapeutic approaches to eliminate or modulate the senescent SASP phenotype for treating age-related salivary gland diseases and extending health span.

Universal interface fluctuations in the contact process.

We study the interface representation of the contact process at its directed-percolation critical point, where the scaling properties of the interface can be related to those of the original particle model. Interestingly, such a behavior happens to be intrinsically anomalous and more complex than that described by the standard Family-Vicsek dynamic scaling Ansatz of surface kinetic roughening. We expand on a previous numerical study by Dickman and Muñoz [Phys. Rev. E 62, 7632 (2000)10.1103/PhysRevE.62.7632] to fully characterize the kinetic roughening universality class for interface dimensions d=1,2, and 3. Beyond obtaining scaling exponent values, we characterize the interface fluctuations via their probability density function (PDF) and covariance, seen to display universal properties which are qualitatively similar to those recently assessed for the Kardar-Parisi-Zhang (KPZ) and other important universality classes of kinetic roughening. Quantitatively, while for d=1 the interface covariance seems to be well described by the KPZ, Airy_{1} covariance, no such agreement occurs in terms of the fluctuation PDF or the scaling exponents.

Differential effects of faces and words in cognitive control in older adults with and without major depressive disorder: An emotional Stroop task study.

Aging and major depressive disorders have been associated with impaired cognitive control. These deficits are also influenced by the affective valence and by the type of stimulus processed. Using an emotional Stroop task, the current study aims to examine cognitive control deficits and their association with emotion regulation in depression and the influence of the type of stimulus (words and faces) in this association. A total of 26 older patients with a major depressive disorder (MDD) (19 women; age range: 65-84 years) and 26 older healthy controls (18 women; age range: 65-80 years) participated in the study. The results showed that MDD individuals presented greater Stroop effects than their healthy controls and an absence of the conflict adaptation effect defined as a reduction of the influence of irrelevant stimulus dimensions after incongruent trials. Additionally, our results also showed that the processing of emotional words in depressed participants is more automatic than the processing of emotional faces. These findings suggest that older depressed individuals have greater difficulty in recognizing affective facial expressions than older healthy controls, while the over-learned behavior of word reading greatly reduces differences in the performance of the emotional Stroop task between groups (MDD and healthy controls).

Large-scale kinetic roughening behavior of coffee-ring fronts.

We have studied the kinetic roughening behavior of the fronts of coffee-ring aggregates via extensive numerical simulations of the off-lattice model considered for this context [Dias et al., Soft Matter 14, 1903 (2018)1744-683X10.1039/C7SM02136D]. This model describes ballistic aggregation of patchy colloids and depends on a parameter r_{AB} which controls the affinity of the two patches, A and B. Suitable boundary conditions allow us to elucidate a discontinuous pinning-depinning transition at r_{AB}=0, with the front displaying intrinsic anomalous scaling, but with unusual exponent values α≃1.2, α_{loc}≃0.5, ß≃1, and z≃1.2. For 00.01 and the system suffers a strong crossover dominated by the r_{AB}=0 behavior for r_{AB}≤0.01. A detailed analysis of correlation functions shows that the aggregate fronts are always in the moving phase for 0

Sex-Driven Differences in the Effectiveness of Individualized Clinical Management of Alzheimer's Disease Risk.

BACKGROUND: The Comparative Effectiveness Dementia and Alzheimer's Registry (CEDAR) trial demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of Alzheimer's disease (AD). As biological sex is a significant risk factor for AD, it is essential to explore the differential effectiveness of targeted clinical interventions in women vs. men. METHODS: Patients were recruited from an Alzheimer's Prevention Clinic. Subjects with normal cognition, subjective cognitive decline, or asymptomatic preclinical AD were classified as "Prevention". Subjects with mild cognitive impairment due to AD or mild AD were classified as "Early Treatment." The primary outcome was the change from baseline to 18-months on the modified-Alzheimer's Prevention Cognitive Composite. Secondary outcomes included a cognitive aging composite, AD and cardiovascular (CV) risk scales, and serum biomarkers. Subjects who adhered to > 60% of recommendations in the CEDAR trial were included in this a priori sub-group analysis to examine whether individualized intervention effects were modified by sex (n=80). RESULTS: In the Prevention group, both women (p=0.0205) and men (p=0.0044) demonstrated improvements in cognition with no sex differences (p=0.5244). In the Early Treatment group, there were also no significant sex differences in cognition (p=0.3299). In the Prevention group, women demonstrated greater improvements in the Multi-Ethnic Study of Atherosclerosis risk score (MESA-RS) than men (difference=1.5, p=0.0013). Women in the Early Treatment group demonstrated greater improvements in CV Risk Factors, Aging and Incidence of Dementia (CAIDE) risk score (difference=2.3, p=0.0067), and the MESA-RS (difference=4.1, p<0.001). CONCLUSIONS: Individualized multi-domain interventions are equally effective at improving cognition in women and men. However, personally-tailored interventions led to greater improvements in calculated AD and CV risk, and CV blood biomarkers, in women compared to men. Future study in larger cohorts is necessary to further define sex differences in AD risk reduction in clinical practice.

Arsenite toxicity is regulated by queuine availability and oxidation-induced reprogramming of the human tRNA epitranscriptome.

Cells respond to environmental stress by regulating gene expression at the level of both transcription and translation. The ∼50 modified ribonucleotides of the human epitranscriptome contribute to the latter, with mounting evidence that dynamic regulation of transfer RNA (tRNA) wobble modifications leads to selective translation of stress response proteins from codon-biased genes. Here we show that the response of human hepatocellular carcinoma cells to arsenite exposure is regulated by the availability of queuine, a micronutrient and essential precursor to the wobble modification queuosine (Q) on tRNAs reading GUN codons. Among oxidizing and alkylating agents at equitoxic concentrations, arsenite exposure caused an oxidant-specific increase in Q that correlated with up-regulation of proteins from codon-biased genes involved in energy metabolism. Limiting queuine increased arsenite-induced cell death, altered translation, increased reactive oxygen species levels, and caused mitochondrial dysfunction. In addition to demonstrating an epitranscriptomic facet of arsenite toxicity and response, our results highlight the links between environmental exposures, stress tolerance, RNA modifications, and micronutrients.

Selenoproteins and the senescence-associated epitranscriptome.

Selenium is a naturally found trace element, which provides multiple benefits including antioxidant, anticancer, and antiaging, as well as boosting immunity. One unique feature of selenium is its incorporation as selenocysteine, a rare 21st amino acid, into selenoproteins. Twenty-five human selenoproteins have been discovered, and a majority of these serve as crucial antioxidant enzymes for redox homeostasis. Unlike other amino acids, incorporation of selenocysteine requires a distinctive UGA stop codon recoding mechanism. Although many studies correlating selenium, selenoproteins, aging, and senescence have been performed, it has not yet been explored if the upstream events regulating selenoprotein synthesis play a role in senescence-associated pathologies. The epitranscriptomic writer alkylation repair homolog 8 (ALKBH8) is critical for selenoprotein production, and its deficiency can significantly decrease levels of selenoproteins that are essential for reactive oxygen species (ROS) detoxification, and increase oxidative stress, one of the major drivers of cellular senescence. Here, we review the potential role of epitranscriptomic marks that govern selenocysteine utilization in regulating the senescence program.

Spreading fronts of wetting liquid droplets: Microscopic simulations and universal fluctuations.

We have used kinetic Monte Carlo (kMC) simulations of a lattice gas to study front fluctuations in the spreading of a nonvolatile liquid droplet onto a solid substrate. Our results are consistent with a diffusive growth law for the radius of the precursor layer, R∼t^{δ}, with δ≈1/2 in all the conditions considered for temperature and substrate wettability, in good agreement with previous studies. The fluctuations of the front exhibit kinetic roughening properties with exponent values which depend on temperature T, but become T independent for sufficiently high T. Moreover, strong evidence of intrinsic anomalous scaling has been found, characterized by different values of the roughness exponent at short and large length scales. Although such a behavior differs from the scaling properties of the one-dimensional Kardar-Parisi-Zhang (KPZ) universality class, the front covariance and the probability distribution function of front fluctuations found in our kMC simulations do display KPZ behavior, agreeing with simulations of a continuum height equation proposed in this context. However, this equation does not feature intrinsic anomalous scaling, at variance with the discrete model.

[CT findings in survivors and non-survivors of COVID-19 and clinical usefulness of a CT scoring system]. / Hallazgos tomográficos entre sobrevivientes y no-sobrevivientes con COVID-19 y utilidad clínica de una puntuación de tomografía torácica.

Background: Many patients with coronavirus disease 2019 (COVID-19) have been diagnosed with computed tomography (CT). A prognostic tool based on CT findings could be useful for predicting death from COVID-19. Objectives: To compare the chest CT findings of patients who survived COVID-19 versus those of patients who died of COVID-19 and to determine the usefulness the clinical usefulness of a CT scoring system for COVID-19. Methods: We included 124 patients with confirmed SARS-CoV-2 infections who were hospitalized between April 1, 2020 and July 25, 2020. Results: Whereas ground-glass opacities were the most common characteristic finding in survivors (75%), crazy paving was the most characteristic finding in non-survivors (65%). Atypical findings were present in 46% of patients. The chest CT score was directly proportional to mortality; a score ≥ 18 was the best cutoff for predicting death, yielding 70% sensitivity (95%CI: 47%-87%). Conclusions: Our results suggest that atypical lesions are more prevalent in this cohort. The chest CT score had high sensitivity for predicting hospital mortality.

Effects on intermittent postural control in people with Parkinson's due to a dual task.

OBJECTIVES: The aim of the present study was to determine the effects of performing a dual task on the sway density plot parameters in Parkinson's disease and control subjects. METHODS: A cross-sectional design was used to establish differences in the mean peak, mean time, and mean distance between a group with Parkinson's disease and a control group without Parkinson's disease. The subjects performed, in a unique measurement session, two trials under three different randomized conditions: i. eyes open, ii. eyes closed, and iii. Eyes open with foam base. One trial was performed as a single task (i.e., the subjects completed one of the balance test), while the other trial was performed as a dual task (i.e., the subjects performed a cognitive task at the same time that they maintained the static balance). RESULTS: There was a group x dual task x condition effect in mean peak (F1.5, 51.1 = 5.21; p = 0.015; η2p = 0.13) and mean time (F1.4, 47.3 = 4.43; p = 0.03; η2p = 0.11) variables. According dual-task cost analysis, there was a main effect of the condition (F6,134 = 2.44; p = 0.05; η2p = 0.34) on MD (F2,68 = 6.90; p < 0.01; η2p = 0.17). CONCLUSIONS: This result indicates differences in the dual task interference in the postural control mechanisms between the Parkinson's disease population and healthy pairs. For easy dual tasks, the Parkinson subjects used anticipatory control responses for longer periods of time, and for more difficult tasks, their control strategy did not change regarding single balance task.

CT findings in survivors and non-survivors of COVID-19 and clinical usefulness of a CT scoring system.

BACKGROUND: Many patients with coronavirus disease 2019 (COVID-19) have been diagnosed with computed tomography (CT). A prognostic tool based on CT findings could be useful for predicting death from COVID-19. OBJECTIVES: To compare the chest CT findings of patients who survived COVID-19 versus those of patients who died of COVID-19 and to determine the usefulness the clinical usefulness of a CT scoring system for COVID-19. METHODS: We included 124 patients with confirmed SARS-CoV-2 infections who were hospitalized between April 1, 2020 and July 25, 2020. RESULTS: Whereas ground-glass opacities were the most common characteristic finding in survivors (75%), crazy paving was the most characteristic finding in non-survivors (65%). Atypical findings were present in 46% of patients. The chest CT score was directly proportional to mortality; a score ≥18 was the best cutoff for predicting death, yielding 70% sensitivity (95%CI: 47%-87%). CONCLUSIONS: Our results suggest that atypical lesions are more prevalent in this cohort. The chest CT score had high sensitivity for predicting hospital mortality.

Hallazgos tomográficos entre sobrevivientes y no-sobrevivientes con COVID-19 y utilidad clínica de una puntuación de tomografía torácica / CT findings in survivors and non-survivors of COVID-19 and clinical usefulness of a CT scoring system

Antecedentes: Muchos pacientes con enfermedad por coronavirus 2019 (COVID-19) han sido diagnosticados mediante tomografía computarizada (TC). Una herramienta de pronóstico obtenida de esta podría ser un predictor útil de mortalidad.ObjetivosEvaluar los hallazgos de la TC de tórax entre los pacientes sobrevivientes y no sobrevivientes con COVID-19 y la utilidad clínica de una puntuación de TC. Métodos: Del 1 de abril al 25 de julio de 2020 se incluyeron 124 pacientes hospitalizados con infección confirmada por SARS-CoV-2. Resultados:Las opacidades en vidrio deslustrado fueron el principal hallazgo típico en los sobrevivientes (75%), mientras que el patrón de “crazy paving” o empedrado fue el principal hallazgo típico en los no sobrevivientes (65%). Los hallazgos atípicos estuvieron presentes hasta en el 46% de los pacientes. Hubo una relación directamente proporcional entre la puntuación de la TC de tórax y la mortalidad, teniendo en cuenta un punto de corte óptimo de la puntuación de la TC de 18 para predecir la muerte con una sensibilidad del 70% [intervalo de confianza (IC) del 95%: 47%-87%]. Conclusiones: Nuestros datos sugieren una mayor prevalencia de lesiones atípicas en esta cohorte. La puntuación de la TC de tórax tuvo una alta sensibilidad para predecir la mortalidad hospitalaria.(AU)

Background: Many patients with coronavirus disease 2019 (COVID-19) have been diagnosed with computed tomography (CT). A prognostic tool based on CT findings could be useful for predicting death from COVID-19. Objectives: To compare the chest CT findings of patients who survived COVID-19 versus those of patients who died of COVID-19 and to determine the usefulness the clinical usefulness of a CT scoring system for COVID-19. Methods: We included 124 patients with confirmed SARS-CoV-2 infections who were hospitalized between April 1, 2020 and July 25, 2020. Results: Whereas ground-glass opacities were the most common characteristic finding in survivors (75%), crazy paving was the most characteristic finding in non-survivors (65%). Atypical findings were present in 46% of patients. The chest CT score was directly proportional to mortality; a score≥18 was the best cutoff for predicting death, yielding 70% sensitivity (95%CI: 47%-87%). Conclusions: Our results suggest that atypical lesions are more prevalent in this cohort. The chest CT score had high sensitivity for predicting hospital mortality.(AU)

Boronate probe-based hydrogen peroxide detection with AlGaN/GaN HEMT sensor.

The results from this study demonstrate the potential of an AlGaN/GaN high electron mobility transistor sensor for the detection of reactive and transient biological molecules such as hydrogen peroxide. A boronate-based fluorescent probe was used with this device to detect the presence of micromolar levels of hydrogen peroxide typically associated with intracellular processes. The real-time electrical response of the high electron mobility transistor sensor showed a gradual decrease in the two-dimensional electron gas current as the reaction proceeded over time. A corresponding increase in the emission intensity was measured from the fluorescent probe with the progression of the reaction. The fluorescence from the boronate probe was used as an indicator to confirm the detection of hydrogen peroxide. These results demonstrate the dynamic measurement capability of AlGaN/GaN high electron mobility transistor sensors in monitoring real-time reactions of reactive oxygen species such as hydrogen peroxide.

How Well Do We Know the Neutron-Matter Equation of State at the Densities Inside Neutron Stars? A Bayesian Approach with Correlated Uncertainties.

We introduce a new framework for quantifying correlated uncertainties of the infinite-matter equation of state derived from chiral effective field theory (χEFT). Bayesian machine learning via Gaussian processes with physics-based hyperparameters allows us to efficiently quantify and propagate theoretical uncertainties of the equation of state, such as χEFT truncation errors, to derived quantities. We apply this framework to state-of-the-art many-body perturbation theory calculations with nucleon-nucleon and three-nucleon interactions up to fourth order in the χEFT expansion. This produces the first statistically robust uncertainty estimates for key quantities of neutron stars. We give results up to twice nuclear saturation density for the energy per particle, pressure, and speed of sound of neutron matter, as well as for the nuclear symmetry energy and its derivative. At nuclear saturation density, the predicted symmetry energy and its slope are consistent with experimental constraints.

Ab Initio Calculations of Low-Energy Nuclear Scattering Using Confining Potential Traps.

A recently modified method to enable low-energy nuclear scattering results to be extracted from the discrete energy levels of the target-projectile clusters confined by harmonic potential traps is tested. We report encouraging results for neutron-α and neutron-^{24}O elastic scattering from analyzing the trapped levels computed using two different ab initio nuclear structure methods. The n-α results have also been checked against a direct ab initio reaction calculation. The n-^{24}O results demonstrate the approach's applicability for a large range of systems provided their spectra in traps can be computed by ab initio methods. A key ingredient is a rigorous understanding of the errors in the calculated energy levels caused by inevitable Hilbert-space truncations in the ab initio methods.

Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype.

IMPACT STATEMENT: Through its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca2+ homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic H2O2 scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression. As Ca2+ is indispensable for secretion from both secretory and non-secretory cells, it is exciting to speculate that the expression of plasma lamellar TRP channels critical for the maintenance of intracellular Ca2+ homeostasis may be coordinately regulated with the SASP.

The epitranscriptomic writer ALKBH8 drives tolerance and protects mouse lungs from the environmental pollutant naphthalene.

The epitranscriptomic writer Alkylation Repair Homolog 8 (ALKBH8) is a transfer RNA (tRNA) methyltransferase that modifies the wobble uridine of selenocysteine tRNA to promote the specialized translation of selenoproteins. Using Alkbh8 deficient (Alkbh8def) mice, we have investigated the importance of epitranscriptomic systems in the response to naphthalene, an abundant polycyclic aromatic hydrocarbon and environmental toxicant. We performed basal lung analysis and naphthalene exposure studies using wild type (WT), Alkbh8def and Cyp2abfgs-null mice, the latter of which lack the cytochrome P450 enzymes required for naphthalene bioactivation. Under basal conditions, lungs from Alkbh8def mice have increased markers of oxidative stress and decreased thioredoxin reductase protein levels, and have reprogrammed gene expression to differentially regulate stress response transcripts. Alkbh8def mice are more sensitive to naphthalene induced death than WT, showing higher susceptibility to lung damage at the cellular and molecular levels. Further, WT mice develop a tolerance to naphthalene after 3 days, defined as resistance to a high challenging dose after repeated exposures, which is absent in Alkbh8def mice. We conclude that the epitranscriptomic writer ALKBH8 plays a protective role against naphthalene-induced lung dysfunction and promotes naphthalene tolerance. Our work provides an early example of how epitranscriptomic systems can regulate the response to environmental stress in vivo.

Loss of epitranscriptomic control of selenocysteine utilization engages senescence and mitochondrial reprogramming☆.

Critically important to the maintenance of the glutathione (GSH) redox cycle are the activities of many selenocysteine-containing GSH metabolizing enzymes whose translation is controlled by the epitranscriptomic writer alkylation repair homolog 8 (ALKBH8). ALKBH8 is a tRNA methyltransferase that methylates the wobble uridine of specific tRNAs to regulate the synthesis of selenoproteins. Here we demonstrate that a deficiency in the writer ALKBH8 (Alkbh8def), alters selenoprotein levels and engages senescence, regulates stress response genes and promotes mitochondrial reprogramming. Alkbh8def mouse embryonic fibroblasts (MEFs) increase many hallmarks of senescence, including senescence associated ß-galactosidase, heterocromatic foci, the cyclin dependent kinase inhibitor p16Ink4a, markers of mitochondrial dynamics as well as the senescence associated secretory phenotype (SASP). Alkbh8def cells also acquire a stress resistance phenotype that is accompanied by an increase in a number redox-modifying transcripts. In addition, Alkbh8def MEFs undergo a metabolic shift that is highlighted by a striking increase in the level of uncoupling protein 2 (UCP2) which enhances oxygen consumption and promotes a reliance on glycolytic metabolism. Finally, we have shown that the Alkbh8 deficiency can be exploited and corresponding MEFs are killed by glycolytic inhibition. Our work demonstrates that defects in an epitransciptomic writer promote senescence and mitochondrial reprogramming and unveils a novel adaptive mechanism for coping with defects in selenocysteine utilization.

Epitranscriptomic systems regulate the translation of reactive oxygen species detoxifying and disease linked selenoproteins.

Here we highlight the role of epitranscriptomic systems in post-transcriptional regulation, with a specific focus on RNA modifying writers required for the incorporation of the 21st amino acid selenocysteine during translation, and the pathologies linked to epitranscriptomic and selenoprotein defects. Epitranscriptomic marks in the form of enzyme-catalyzed modifications to RNA have been shown to be important signals regulating translation, with defects linked to altered development, intellectual impairment, and cancer. Modifications to rRNA, mRNA and tRNA can affect their structure and function, while the levels of these dynamic tRNA-specific epitranscriptomic marks are stress-regulated to control translation. The tRNA for selenocysteine contains five distinct epitranscriptomic marks and the ALKBH8 writer for the wobble uridine (U) has been shown to be vital for the translation of the glutathione peroxidase (GPX) and thioredoxin reductase (TRXR) family of selenoproteins. The reactive oxygen species (ROS) detoxifying selenocysteine containing proteins are a prime examples of how specialized translation can be regulated by specific tRNA modifications working in conjunction with distinct codon usage patterns, RNA binding proteins and specific 3' untranslated region (UTR) signals. We highlight the important role of selenoproteins in detoxifying ROS and provide details on how epitranscriptomic marks and selenoproteins can play key roles in and maintaining mitochondrial function and preventing disease.