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The electrostatic interaction of RNA with its aqueous environment is most relevant for defining macromolecular structure and biological function. The attractive interaction of phosphate groups in the RNA backbone with ions in the water environment leads to the accumulation of positively charged ions in the first few hydration layers around RNA. Electrostatics of this ion atmosphere and the resulting ion concentration profiles have been described by solutions of the nonlinear Poisson-Boltzmann equation and atomistic molecular dynamics (MD) simulations. Much less is known on contact pairs of RNA phosphate groups with ions at the RNA surface, regarding their abundance, molecular geometry, and role in defining RNA structure. Here, we present a combined theoretical and experimental study of interactions of a short RNA duplex with magnesium (Mg2+) ions. MD simulations covering a microsecond time range give detailed hydration geometries as well as electrostatics and spatial arrangements of phosphate-Mg2+pairs, including both pairs in direct contact and separated by a single water layer. The theoretical predictions are benchmarked by linear infrared absorption and nonlinear two-dimensional infrared spectra of the asymmetric phosphate stretch vibration which probes both local interaction geometries and electric fields. Contact pairs of phosphate groups and Mg2+ions are identified via their impact on the vibrational frequency position and line shape. A quantitative analysis of infrared spectra for a range of Mg2+-excess concentrations and comparison with fluorescence titration measurements shows that on average 20–30% of the Mg2+ions interacting with the RNA duplex form contact pairs. The experimental and MD results are in good agreement. In contrast, calculations based on the nonlinear Poisson-Boltzmann equation fail in describing the ion arrangement, molecular electrostatic potential, and local electric field strengths correctly. Our results underline the importance of local electric field mapping and molecular-level simulations to correctly account for the electrostatics at the RNA-water interface.

AbstractThe Adverse Childhood Experience (ACE) Questionnaire is one of the most widely used assessments for trauma exposure and adversity experienced during the first 18 years of life (Felitti et al., 1998; Kia-Keating et al., 2019). While the ACE Questionnaire has shown to have good reliability and validity, inconsistencies have been demonstrated for the test-retest form of reliability (MacKenzie et al., 2005; Pinto et al., 2014; Zanotti et al., 2018). To address the lack of consensus on the test-retest reliability of the ACE Questionnaire and the appropriateness for use with adolescents, the current study examined test-retest reliability of the ACE measure for a small group of adolescents in residential treatment. Participants (n = 20) completed the ACE during week 1 and were later assessed at week 9. The test-retest reliability of the ACE was very high (r = 0.913), thereby supporting the overall reliability of the ACE questionnaire and its effectiveness in identifying baseline trauma. However, the results indicate that adolescents might not fully understand their past trauma experiences prior to receiving trauma-focused treatment. Potential explanations of unreliable reporting of ACEs, counseling implications and recommendations for multiple administrations are discussed.

ABSTRACTEnglish-language commentary on the role of the French Revolution in Hegel’s Phenomenology of Spirittends to equate the so-called “fury of destruction” (Furie des Verschwindens) with the violent dialectic of rival factions’ rush for power. Here it is argued that “Absolute Freedom and Terror” ought instead to be read in the light of a “fury of disappearance”, namely in terms of the extinction of dissenting citizens’ legal personhood. This is achieved by recourse to civil death, a criminal sentence that declares the individual, who is very much alive, legally dead. While there are some actual and quite painful consequences for recipients of such a sentence, civil death is effective mainly on the philosophical and constitutional planes, where it maintains the illusion of a unanimous general will, fleetingly securing the state from failure. A focus on personhood and civil death also taps into the larger Hegelian dialectic of legalism and tradition, and into the various shapes community life takes therein, beginning with Greek Ethical Life, and ending in Absolute Freedom and Terror.

There is no known biological requirement for germanium (Ge), germanates, or any organogermanium compound. Ge deficiency has not been demonstrated in any animal. The estimated average dietary intake of Ge in humans is 1.5 mg/d. Ge is widely distributed in edible foods, all of which, with few exceptions, contain less than 5 ppm Ge, since higher levels are toxic to most plants. Ingestion of Ge compounds has been shown to produce toxic effects in experimental animals. [ABSTRACT FROM AUTHOR]

The extent of contact and solvent shared ion pairs of phosphate groups with Na+, Ca2+and Mg2+ions in aqueous environment and their relevance for the stability of polyanionic DNA and RNA structures is highly debated. Employing the asymmetric phosphate stretching vibration of dimethyl phosphate (DMP), a model system of the sugar-phosphate backbone of DNA and RNA, we present linear infrared, femtosecond infrared pump-probe and absorptive 2D-IR spectra that report on contact ion pair formation via the presence of blue shifted spectral signatures. Compared to the linear infrared spectra, the nonlinear spectra reveal contact ion pairs with increased sensitivity because the spectra accentuate differences in peak frequency, transition dipole moment strength, and excited state lifetime. The experimental results are corroborated by long time scale MD simulations, benchmarked by density functional simulations on phosphate-ion-water clusters. The microscopic interpretation reveals subtle structural differences of ion pairs formed by the phosphate group and the ions Na+, Ca2+and Mg2+. Intricate properties of the solvation shell around the phosphate group and the ion are essential to explain the experimental observations. The present work addresses a challenging to probe topic with the help of a model system and establishes new experimental data of contact ion pair formation, thereby underlining the potential of nonlinear 2D-IR spectroscopy as an analytical probe of phosphate-ion interactions in complex biological systems.

AbstractAlthough associations between developmental trauma, juvenile justice involvement and youth substance use have been previously reported in the published literature, the interconnection among these three factors has not been adequately studied. This article describes the interconnection among these three factors and calls for greater attention to the role of adverse childhood experiences (ACEs) in the diagnosis and treatment of youth who present with histories of substance use and/or offending behavior. Pilot data are presented that show high rates of self-reported trauma exposure, substance use history, justice involvement, and mental health problems in a sample of adolescents in residential treatment. The data point to the need for residential treatment centers to consider trauma histories in developing treatment plans for youth with current and prior substance use and offending behavior.

We extend a call-by-need variant of PCF with a binary probabilistic fair choice operator, which makes a lazy and typed variant of probabilistic functional programming. We define a contextual equivalence that respects the expected convergence of expressions and prove a corresponding context lemma. This enables us to show correctness of several program transformations with respect to contextual equivalence. Distribution-equivalence of expressions of numeric type is introduced. While the notion of contextual equivalence stems from program semantics, the notion of distribution equivalence is a direct description of the stochastic model. Our main result is that both notions are compatible: We show that for closed expressions of numeric type contextual equivalence and distribution-equivalence coincide. This provides a strong and often operationally feasible criterion for contextual equivalence of expressions and programs.

Objective:Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleraceaMart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoriaMart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition.Methods:Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established.Results:Results indicated significant reductions (P<0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats.Discussion:In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

Resistance toward CD95-mediated apoptosis is a hallmark of many different malignancies, as it is known from primary chronic lymphocytic leukemia (CLL) cells. Previously, we could show that miR-138 and -424 are downregulated in CLL cells. Here, we identified 2 new target genes, namely acyl protein thioesterase (APT) 1 and 2, which are under control of both miRs and thereby significantly overexpressed in CLL cells. APTs are the only enzymes known to promote depalmitoylation. Indeed, membrane proteins are significantly less palmitoylated in CLL cells compared with normal B cells. We identified APTs to directly interact with CD95 to promote depalmitoylation, thus impairing apoptosis mediated through CD95. Specific inhibition of APTs by siRNAs, treatment with miRs-138/-424, and pharmacologic approaches restore CD95-mediated apoptosis in CLL cells and other cancer cells, pointing to an important regulatory role of APTs in CD95 apoptosis. The identification of the depalmitoylation reaction of CD95 by APTs as a microRNA (miRNA) target provides a novel molecular mechanism for how malignant cells escape from CD95-mediated apoptosis. Here, we introduce palmitoylation as a novel posttranslational modification in CLL, which might impact on localization, mobility, and function of molecules, survival signaling, and migration.

The present study examines whether the frequency of an error-bearing word and its predictability, arising from sentential constraints and text familiarity, either independently or jointly, would impair error detection by making proofreading driven by top-down processes. Prior to a proofreading task, participants were asked to read, copy, memorize, or paraphrase sentences, half of which contained errors. These tasks represented a continuum of progressively more demanding and time-consuming activities, which were thought to lead to comparable increases in text familiarity and thus predictability. Proofreading times were unaffected by whether the sentences had been encountered earlier. Proofreading was slower and less accurate for high-frequency words and for highly constrained sentences. Prior memorization produced divergent effects on accuracy depending on sentential constraints. The latter finding suggested that a substantial level of predictability, such as that produced by memorizing highly constrained sentences, can increase the probability of overlooking errors.

Various static analyses of functional programming languages that permit infinite data structures make use of set constants like Top, Inf, and Bot, denoting all terms, all lists not eventually ending in Nil, and all non-terminating programs, respectively. We use a set language that permits union, constructors and recursive definition of set constants with a greatest fixpoint semantics in the set of all, also infinite, computable trees, where all term constructors are non-strict. This paper proves decidability, in particular DEXPTIME-completeness, of inclusion of co-inductively defined sets by using algorithms and results from tree automata and set constraints. The test for set inclusion is required by certain strictness analysis algorithms in lazy functional programming languages and could also be the basis for further set-based analyses.

Abstract: We present an observational semantics for , a concurrent λ-calculus with reference cells and futures. The calculus models the operational semantics of the concurrent higher-order programming language Alice ML. Our result is a powerful notion of equivalence that is the coarsest nontrivial congruence distinguishing observably different processes. It justifies a maximal set of correct program transformations, and it includes all of ''s deterministic reduction rules, in particular, call-by-value β-reduction. [Copyright &y& Elsevier]

Lower body exercises are an important intervention in retraining balance. The aquatic environment has been identified as an appropriate medium to perform these exercises. The purpose of this research was to determine if aquatic exercise was more effective than landbased exercise when training balance.