DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory.

The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here, we report that G-quadruplex DNA (G4-DNA) accumulates in neurons, in an experience-dependent manner, and that this is required for the transient silencing and activation of genes that are critically involved in learning and memory in male C57/BL6 mice. In addition, site-specific resolution of G4-DNA by dCas9-mediated deposition of the helicase DHX36 impairs fear extinction memory. Dynamic DNA structure states therefore represent a key molecular mechanism underlying memory consolidation.One-Sentence Summary: G4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.

Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory.

The RNA modification N6-methyladenosine (m6A) regulates the interaction between RNA and various RNA binding proteins within the nucleus and other subcellular compartments and has recently been shown to be involved in experience-dependent plasticity, learning, and memory. Using m6A RNA-sequencing, we have discovered a distinct population of learning-related m6A- modified RNAs at the synapse, which includes the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1). RNA immunoprecipitation and mass spectrometry revealed 12 new synapse-specific learning-induced m6A readers in the mPFC of male C57/BL6 mice, with m6A-modified Malat1 binding to a subset of these, including CYFIP2 and DPYSL2. In addition, a cell type- and synapse-specific, and state-dependent, reduction of m6A on Malat1 impairs fear-extinction memory; an effect that likely occurs through a disruption in the interaction between Malat1 and DPYSL2 and an associated decrease in dendritic spine formation. These findings highlight the critical role of m6A in regulating the functional state of RNA during the consolidation of fear-extinction memory, and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.SIGNIFICANCE STATEMENT We have discovered that learning-induced m6A-modified RNA (including the long noncoding RNA, Malat1) accumulates in the synaptic compartment. We have identified several new m6A readers that are associated with fear extinction learning and demonstrate a causal relationship between m6A-modified Malat1 and the formation of fear-extinction memory. These findings highlight the role of m6A in regulating the functional state of an RNA during memory formation and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.

High-Pressure Synthesis and Recovery of Single Crystals of the Metastable Manganese Carbide, MnCx.

Transition metal carbides find widespread use throughout industry due to their high strength and resilience under extreme conditions. However, they remain largely limited to compounds formed from the early d-block elements, since the mid-to-late transition metals do not form thermodynamically stable carbides. We report here the high-pressure bulk synthesis of large single crystals of a novel metastable manganese carbide compound, MnCx (P63/mmc), which adopts the anti-NiAs-type structure with significant substoichiometry at the carbon sites. We demonstrate how synthesis pressure modulates the carbon loading, with ~40 % occupancy being achieved at 9.9 GPa.

Localised Cdr1as activity is required for fear extinction memory.

Circular RNAs (circRNAs) comprise a novel class of regulatory RNAs that are abundant in the brain, particularly within synapses. They are highly stable, dynamically regulated, and display a range of functions, including serving as decoys for microRNAs and proteins and, in some cases, circRNAs also undergo translation. Early work in animal models revealed an association between circRNAs and neurodegenerative and neuropsychiatric disorders; however, little is known about the link between circRNA function and memory. To address this, we examined circRNA in synaptosomes derived from the medial prefrontal cortex of fear extinction-trained male C57BL/6J mice and found 12,837 circRNAs that were enriched at the synapse, including cerebellar degeneration-related protein 1 antisense RNA (Cdr1as). Targeted knockdown of Cdr1as in the neural processes of the infralimbic cortex led to impaired fear extinction memory. These findings highlight the involvement of localised circRNA activity at the synapse in memory formation.

Introducing a common taxonomy to support learning from failure in conservation.

Although some sectors have made significant progress in learning from failure, there is currently limited consensus on how a similar transition could best be achieved in conservation and what is required to facilitate this. One of the key enabling conditions for other sectors is a widely accepted and standardized classification system for identifying and analyzing root causes of failure. We devised a comprehensive taxonomy of root causes of failure affecting conservation projects. To develop this, we solicited examples of real-life conservation efforts that were deemed to have failed in some way, identified their underlying root causes of failure, and used these to develop a generic, 3-tier taxonomy of the ways in which projects fail, at the top of which are 6 overarching cause categories that are further divided into midlevel cause categories and specific root causes. We tested the taxonomy by asking conservation practitioners to use it to classify the causes of failure for conservation efforts they had been involved in. No significant gaps or redundancies were identified during this testing phase. We then analyzed the frequency that particular root causes were encountered by projects within this test sample, which suggested that some root causes were more likely to be encountered than others and that a small number of root causes were more likely to be encountered by projects implementing particular types of conservation action. Our taxonomy could be used to improve identification, analysis, and subsequent learning from failed conservation efforts, address some of the barriers that currently limit the ability of conservation practitioners to learn from failure, and contribute to establishing an effective culture of learning from failure within conservation.

Introducción de una taxonomía común como apoyo al aprendizaje a partir del fracaso en la conservación Resumen Mientras que algunos sectores han progresado significativamente en el aprendizaje a partir del fracaso, actualmente hay un consenso limitado sobre cómo podría lograrse una transición similar en la conservación y qué se requiere para facilitarla. Una de las condiciones habilitantes más importantes en otros sectores es un sistema de clasificación estandarizado y aceptado por la mayoría para la identificación y análisis de las causas fundamentales del fracaso. Diseñamos una taxonomía completa de las causas fundamentales del fracaso que afecta a los proyectos de conservación. Para desarrollarla, solicitamos ejemplos de esfuerzos de conservación reales que de alguna manera se consideraron como fracasos, identificamos las causas fundamentales no aparentes de su fracaso y luego las usamos para desarrollar una taxonomía genérica de tres niveles de las maneras en las que fracasan los proyectos, en cuyo nivel superior están seis categorías de causas generales que después se dividen en categorías de nivel medio de categorías de causas y causas fundamentales específicas. Pusimos a prueba la taxonomía al pedirle a los practicantes de la conservación que la usaran para clasificar las causas del fracaso de los esfuerzos de conservación en los que han participado. No identificamos vacíos o redundancias importantes durante esta fase de prueba. Después, analizamos la frecuencia con la que los proyectos de esta muestra se enfrentaron a causas fundamentales particulares, lo que sugirió que algunas causas fundamentales tienen mayor probabilidad de ocurrir y que un número reducido de causas fundamentales tiene mayor probabilidad de ocurrir en proyectos que implementan ciertos tipos de acciones de conservación. Nuestra taxonomía podría usarse para mejorar el análisis, identificación y aprendizaje subsecuente a partir del fracaso de los esfuerzos de conservación; tratar algunas de las barreras que en la actualidad limitan a los practicantes de la conservación a aprender del fracaso; y contribuir al establecimiento de una cultura efectiva del aprendizaje a partir del fracaso dentro de la conservación.

Probing High-Temperature Amine Chemistry: Is the Reaction NH3 + NH2 ⇄ N2H3 + H2 Important?

The reaction NH3 + NH2 ⇄ N2H3 + H2 (R1) has been identified as a key step to explain experimental results for pyrolysis and oxidation of ammonia. However, no direct experimental or theoretical evidence for the reaction has been reported. In the present work, the reaction was studied by ab initio theory and by reinterpretation of experimental data. We could not locate a transition state for R1 occurring as a direct process, but alternative mechanisms yielded an upper bound to k1 of 1.5 × 1013 exp(-58.9 kcal mol-1/RT) cm3 mol-1 s-1 over 1000-2500 K, several orders of magnitude lower than values applied in modeling. Consistent with the theoretical work, re-evaluation of NH3 pyrolysis data supported a very low value of k1. However, this finding opens up a novel unresolved issue. Current kinetic models cannot capture the NH3 oxidation behavior in a number of laminar flow reactor and jet-stirred reactor experiments without adopting an improbably high value for k1. Important oxidation steps might be underestimated or missing from mechanisms.

Re-Examination of the N2O + O Reaction.

The reaction of N2O with O is a key step in consumption of nitrous oxide in thermal processes. It has two product channels, NO + NO (R2) and N2 + O2 (R3). The rate constant for R2 has been measured both in the forward and the reverse direction at elevated temperature and is well established. However, the rate constant for the N2 + O2 channel (R3) has been difficult to quantify and has significant error limits. The direct reaction on the triplet surface has a barrier of around 40 kcal mol-1, and it is too slow for the N2 + O2 channel to have any practical significance. Recently, Pham and Lin (2022) suggested an alternative low activation energy reaction path that involves intersystem crossing and reaction on the singlet surface. In the present work, we re-examined a wide range of experiments relevant for the N2O + O reaction through kinetic modeling, paying attention to the impact of artifacts such as impurities and surface reactions. Experimental results from shock tubes and batch reactors on the final NO yield in N2O decomposition, covering temperatures of 973-2200 K and pressures of 0.013-11.5 atm, support k3 ∼ 0, consistent with the high activation energy for reaction on the triplet surface and a low probability of ISC.

Measurement of the Intramolecular Hydrogen-Shift Rate Coefficient for the CH3SCH2OO Radical between 314 and 433 K.

The intramolecular hydrogen-shift rate coefficient of the CH3SCH2O2 (methylthiomethylperoxy, MSP) radical, a product formed in the oxidation of dimethyl sulfide (DMS), was measured using a pulsed laser photolysis flow tube reactor coupled to a high-resolution time-of-flight chemical ionization mass spectrometer that measured the formation of the DMS degradation end product HOOCH2SCHO (hydroperoxymethyl thioformate). Measurements performed over the temperature range of 314-433 K yielded a hydrogen-shift rate coefficient of k1(T) = (2.39 ± 0.7) × 109 exp(-(7278 ± 99)/T) s-1 Arrhenius expression and a value extrapolated to 298 K of 0.06 s-1. The potential energy surface and the rate coefficient have also been theoretically investigated using density functional theory at the M06-2X/aug-cc-pVTZ level combined with approximate CCSD(T)/CBS energies yielding k1(273-433 K) = 2.4 × 1011 × exp(-8782/T) s-1 and k1(298 K) = 0.037 s-1 in fair agreement with the experimental results. Present results are compared with the previously reported values of k1(293-298 K).

The interplay between suicidal experiences, psychotic experiences and interpersonal relationships: a qualitative study.

BACKGROUND: Suicidal thoughts, acts, plans and deaths are considerably more prevalent in people with non-affective psychosis, including schizophrenia, compared to the general population. Social isolation and interpersonal difficulties have been implicated in pathways which underpin suicidal experiences in people with severe mental health problems. However, the interactions between psychotic experiences, such as hallucinations and paranoia, suicidal experiences, and the presence, and indeed, absence of interpersonal relationships is poorly understood and insufficiently explored. The current study sought to contribute to this understanding. METHODS: An inductive thematic analysis was conducted on transcripts of 22, individual, semi-structured interviews with adult participants who had both non-affective psychosis and recent suicidal experiences. A purposive sampling strategy was used. Trustworthiness of the analysis was assured with researcher triangulation. RESULTS: Participants relayed both positive and negative experiences of interpersonal relationships. A novel conceptual model is presented reflecting a highly complex interplay between a range of different suicidal experiences, psychosis, and aspects of interpersonal relationships. Three themes fed into this interplay, depicting dynamics between perceptions of i. not mattering and mattering, ii. becoming disconnected from other people, and iii. constraints versus freedom associated with sharing suicidal and psychotic experiences with others. CONCLUSION: This study revealed a detailed insight into ways in which interpersonal relationships are perceived to interact with psychotic and suicidal experiences in ways that can be both beneficial and challenging. This is important from scientific and clinical perspectives for understanding the complex pathways involved in suicidal experiences. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03114917), 14th April 2017. ISRCTN (reference ISRCTN17776666 .); 5th June 2017). Registration was recorded prior to participant recruitment commencing.

First record of Boulenger's anthias Sacura boulengeri (Heemstra 1973) in the Red Sea.

In November 2020, we observed several individuals and collected one juvenile of an unidentified anthiadine fish (Serranidae) between depths of 250 and 307 m near vertical walls of rocky reefs in the northern Red Sea. Further morphological and molecular analyses revealed that the collected specimen matches Sacura boulengeri, a species previously reported only from the Gulf of Oman to India.

Experimental and computational studies of the kinetics of the reaction of hydrogen peroxide with the amidogen radical.

The pulsed-laser photolysis/laser-induced fluorescence method is used to study the kinetics of the reaction of NH2 with H2O2 to yield a second-order rate constant of (2.42 ± 0.55) × 10-14 cm3 molecule-1 s-1 at 412 K in 10-22 mbar of Ar bath gas. There are no prior measurements for comparison. To check this value and enable reliable extrapolation to other temperatures, we also compute thermal rate constants for this process over the temperature range 298-3000 K via multi-structural canonical variational transition-state theory with small-curvature multidimensional tunneling (MS-CVT/SCT). The CVT/SCT rate constants are derived using a dual-level direct dynamics approach utilizing single-point CCSD(T)-F12b/cc-pVQZ-F12 energies-corrected for core-valence and scalar relativistic effects-and M06-2X/MG3S geometries, gradients, and Hessians-for all stationary and non-stationary points along the reaction path. The multistructural method with torsional anharmonicity, based on a coupled torsional potential, is then employed to calculate correction factors for the rate constants, accounting for the comprehensive effects of torsional anharmonicity on the kinetics of this reaction system. The final MS-CVT/SCT rate constants are found to be in good agreement with our measurements and can be expressed in modified Arrhenius form as 2.13 × 10-15 (T/298 K)4.02 exp(-513 K/T) cm3 molecule-1 s-1 over the temperature range of 298-3000 K.

Does a powerlifting inspired exercise programme better compliment pain education compared to bodyweight exercise for people with chronic low back pain? A multicentre, single-blind, randomised controlled trial.

BACKGROUND: Contemporary management of chronic low back pain involves combined exercise and pain education. Currently, there is a gap in the literature for whether any exercise mode better pairs with pain education. The purpose of this study was to compare general callisthenic exercise with a powerlifting style programme, both paired with consistent pain education, for chronic low back pain. We hypothesised powerlifting style training may better compliment the messages of pain education. METHODS: An 8-week single-blind randomised controlled trial was conducted comparing bodyweight exercise (n = 32) with powerlifting (n = 32) paired with the same education, for people with chronic low back pain. Exercise sessions were one-on-one and lasted 60-min, with the last 5-15 min comprising pain education. Pain, disability, fear, catastrophizing, self-efficacy, anxiety, and depression were measured at baseline, 8-weeks, 3-months, and 6-months. RESULTS: No significant between-group differences were observed for pain (p≥0.40), or disability (p≥0.45) at any time-point. Within-group differences were significantly improved for pain (p ≤ 0.04) and disability (p ≤ 0.04) at all time-points for both groups, except 6-month disability in the bodyweight group (p = 0.1). Behavioural measures explained 39-60% of the variance in changes in pain and disability at each time-point, with fear and self-efficacy emerging as significant in these models (p ≤ 0.001). CONCLUSIONS: Both powerlifting and bodyweight exercise were safe and beneficial when paired with pain education for chronic low back pain, with reductions in pain and disability associated with improved fear and self-efficacy. This study provides opportunity for practitioners to no longer be constrained by systematic approaches to chronic low back pain.

Fatigability of the knee extensors following high- and low-load resistance exercise sessions in trained men.

PURPOSE: Fatigability after gym-based resistance exercises with high and low loads has not been well described, thus limiting the translation of exhaustive low-weight prescription into athletic practice. We compared the fatigability and recovery of the knee extensor muscles for up to 1H after sessions that involved either high- or low-load resistance exercises. METHODS: 16 trained men performed two resistance exercise sessions between 5 and 7 days apart. The LIGHT session involved five sets to task failure at 50% of maximal knee-extension strength, whereas the HEAVY session accrued repetitions across seven sets at intensities ≥ 80% maximal knee-extension strength. Measures of quadriceps maximal torque and rate of torque development were measured before, after, and 1H after each exercise session. Muscle activation (electromyography and voluntary activation) and contractility were measured from doublet stimulation of the femoral nerve during and after maximal contractions, respectively. RESULTS: Greater declines in maximal rate of torque development were observed after the LIGHT compared with the HEAVY session (p < 0.001), with full recovery after 1H. Voluntary activation (100-Hz doublet stimulation) and surface electromyograms were reduced immediately after the HEAVY session only (p < 0.05), with greater declines in quadriceps twitch amplitudes after the LIGHT session (p < 0.01). Voluntary activation (100-Hz doublet stimulation) was reduced at 1H after both the HEAVY and LIGHT sessions (p < 0.05). CONCLUSIONS: Despite differences in the decreases in muscle activation and contractility after high- and low-load resistance-exercise sessions, recovery of neuromuscular function was essentially complete after 1H of rest for both sessions.

Gas-Phase Chemistry of 1,1,2,3,3,4,4-Heptafluorobut-1-ene Initiated by Chlorine Atoms.

The possibility of mitigating climate change by switching to materials with low global warming potentials motivates a study of the spectroscopic and kinetic properties of a fluorinated olefin. The relative rate method was used to determine the rate constant for the reaction of heptafluorobut-1-ene (CF2=CFCF2CF2H) with chlorine atoms in air. A mercury UV lamp was used to generate atomic chlorine, which initiated chemistry monitored by FTIR spectroscopy. Ethane was used as the reference compound for kinetic studies. Oxidation of heptafluorobut-1-ene initiated by a chlorine atom creates carbonyl difluoride (CF2=O) and 2,2,3,3 tetrafluoropropanoyl fluoride (O=CFCF2CF2H) as the major products. Anharmonic frequency calculations allowing for several low-energy conformations of 1,1,2,3,3,4,4 heptafluorobut-1-ene and 2,2,3,3 tetrafluoropropanoyl fluoride, based on density functional theory, are in good accord with measurements. The global warming potentials of these two molecules were calculated from the measured IR spectra and estimated atmospheric lifetimes and found to be small, less than 1.

Declines in muscle contractility and activation during isometric contractions of the knee extensors vary with contraction intensity and exercise volume.

NEW FINDINGS: What is the central question of this study? Is there a critical threshold beyond which the loss of muscle contractility is regulated by the level of muscle activation during single-limb exercise of differing intensities and volumes? What is the main finding and its importance? Plateaus in the decline in muscle contractility during single-limb knee extension depended on both exercise volume and contraction intensity.  A plateau was only evident with an increase in exercise volume.  Muscle activation increased and did not decline despite substantial reductions in contractility. The findings indicate that the decrease in muscle contractility exhibited by resistance-trained men during the performance of submaximal isometric contractions with the knee extensors was not regulated by the level of muscle activation. ABSTRACT: Our study examined the influence of contraction intensity and exercise volume on changes in muscle contractility and activation of the knee extensor muscles. Maximal voluntary torque (MVT) and rate of change in torque, surface electromyograms, voluntary activation, V-waves and quadriceps resting twitch measures were assessed in 10 resistance-trained men during two experimental sessions. Each session began with an initial baseline series of contractions at a fixed intensity of 40% or 80% MVT. The 40%-only session continued with five contractions to task failure at 40% MVT. The 80% session continued with five contractions to failure each at 80%, 60% and 40% MVT. Greater reductions in MVT were observed during the baseline contractions of the 40%-only session compared with the 80% session at each matched-volume time point (P < 0.05), with similar changes in twitch values (P < 0.001). MVT and twitch values plateaued at each intensity during the 80% session and were significantly different across intensities: 80% > 60% > 40% (P < 0.001). There were no differences for measures during the five contractions at 40% MVT performed on the different days, despite a greater volume of exercise performed prior to the 40% MVT during the 80% session. At each contraction intensity, a plateau in contractility loss was observed as more contractions were performed. We found that initial increases in muscle activation were maintained in the presence of increases in exercise volume and, in contrast to the critical-threshold hypothesis, did not decline in parallel with reductions in muscle contractility.

Kinetic fall-off behavior for the Cl + Furan-2,5-dione (C4H2O3, maleic anhydride) reaction.

Rate coefficients, k, for the gas-phase Cl + Furan-2,5-dione (C4H2O3, maleic anhydride) reaction were measured over the 15-500 torr (He and N2 bath gas) pressure range at temperatures between 283 and 323 K. Kinetic measurements were performed using pulsed laser photolysis (PLP) to produce Cl atoms and atomic resonance fluorescence (RF) to monitor the Cl atom temporal profile. Complementary relative rate (RR) measurements were performed at 296 K and 620 torr pressure (syn. air) and found to be in good agreement with the absolute measurements. A Troe-type fall-off fit of the temperature and pressure dependence yielded the following rate coefficient parameters: ko(T) = (9.4 ± 0.5) × 10-29 (T/298)-6.3 cm6 molecule-2 s-1, k∞(T) = (3.4 ± 0.5) × 10-11 (T/298)-1.4 cm3 molecule-1 s-1. The formation of a Cl·C4H2O3 adduct intermediate was deduced from the Cl atom temporal profiles and an equilibrium constant, KP(T), for the Cl + C4H2O3 ↔ Cl·C4H2O3 reaction was determined. A third-law analysis yielded ΔH = -15.7 ± 0.4 kcal mol-1 with ΔS = -25.1 cal K-1 mol-1, where ΔS was derived from theoretical calculations at the B3LYP/6-311G(2d,p,d) level. In addition, the rate coefficient for the Cl·C4H2O3 + O2 reaction at 296 K was measured to be (2.83 ± 0.16) × 10-12 cm3 molecule-1 s-1, where the quoted uncertainty is the 2σ fit precision. Stable end-product molar yields of (83 ± 7), (188 ± 10), and (65 ± 10)% were measured for CO, CO2, and HC(O)Cl, respectively, in an air bath gas. An atmospheric degradation mechanism for C4H2O3 is proposed based on the observed product yields and theoretical calculations of ring-opening pathways and activation barrier energies at the CBS-QB3 level of theory.

Fatigue, pain, and the recovery of neuromuscular function after consecutive days of full-body resistance exercise in trained men.

PURPOSE: This study measured the self-reported level of fatigue, pain, and neuromuscular function of the knee extensor muscles over a three-day period that included two consecutive days of full-body resistance exercises. METHODS: 10 resistance-trained men performed two consecutive days of full-body resistance exercise. Muscle activation (electromyography and voluntary activation), contractility, and presynaptic inhibition of Ia afferents (homosynaptic and GABA mediated presynaptic inhibition) for the quadriceps were examined from femoral and posterior tibial nerve stimulation. RESULTS: Fatigue and pain were elevated after Day 1, and were not reduced to pre-exercise levels at the start of Day 2 (p < 0.05). Maximal voluntary torque (- 51.4 Nm, 95% CI = 12.4-90.4 Nm, p = 0.005) and rate of torque development (- 469 Nm.s-1, 95% CI = 109-829 Nm.s-1, p = 0.006) were reduced after Day 1, had recovered by Day 2, and did not change after the second training session. The maximal amplitude and rate of rise for the quadriceps twitch were reduced after both training sessions (p < 0.01), with recovery 24 h each session. The maximal amplitude and rate of early muscle activation were reduced after Day 1 (p < 0.01), but no changes were observed for voluntary activation, H-reflex size and shape, or measures of Ia presynaptic inhibition. CONCLUSION: Resistance exercise in the presence of elevated fatigue and pain from a previous training session does not worsen recovery, or lead to significant alterations in quadriceps neuromuscular function. Reduction in muscle contractility, in the absence of declines in muscle activation, does not lead to decreased voluntary torque.

The DNA Repair-Associated Protein Gadd45γ Regulates the Temporal Coding of Immediate Early Gene Expression within the Prelimbic Prefrontal Cortex and Is Required for the Consolidation of Associative Fear Memory.

We have identified a member of the growth arrest and DNA damage (Gadd45) protein family, Gadd45γ, which is known to be critically involved in DNA repair, as a key player in the regulation of immediate early gene (IEG) expression underlying the consolidation of associative fear memory in adult male C57BL/6 mice. Gadd45γ temporally influences learning-induced IEG expression in the prelimbic prefrontal cortex (PLPFC) through its interaction with DNA double-strand break (DSB)-mediated changes in DNA methylation. Our findings suggest a two-hit model of experience-dependent IEG activity and learning that comprises (1) a first wave of IEG expression governed by DSBs and followed by a rapid increase in DNA methylation, and (2) a second wave of IEG expression associated with the recruitment of Gadd45γ and active DNA demethylation at the same site, which is necessary for memory consolidation.SIGNIFICANCE STATEMENT How does the pattern of immediate early gene transcription in the brain relate to the storage and accession of information, and what controls these patterns? This paper explores how Gadd45γ, a gene that is known to be involved with DNA modification and repair, regulates the temporal coding of IEGs underlying associative learning and memory. We reveal that, during fear learning, Gadd45γ serves to act as a coordinator of IEG expression and subsequent memory consolidation by directing temporally specific changes in active DNA demethylation at the promoter of plasticity-related IEGs.

Climate Metrics for C1-C4 Hydrofluorocarbons (HFCs).

Hydrofluorocarbons (HFCs) are potent greenhouse gases that are potential substitutes for ozone depleting substances. The Kigali amendment lists 17 HFCs that are currently in commercial use to be regulated under the Montreal Protocol. Future commercial applications may explore the use of other HFCs, most of which currently lack an evaluation of their climate metrics. In this work, atmospheric lifetimes, radiative efficiencies (REs), global warming potentials (GWPs), and global temperature change potentials (GTPs) for all saturated HFCs with fewer than 5 carbon atoms are estimated to help guide future usage and policy decisions. Atmospheric lifetimes were estimated using a structure activity relationship (SAR) for OH radical reactivity and estimated O(1D) reactivity. Radiative metrics were obtained using theoretically calculated infrared absorption spectra that were presented in a previous work. Calculations for some additional HFCs not included in the previous work were performed in this work. The HFCs display unique infrared spectra with strong absorption in the Earth's atmospheric infrared window region, primarily due to the C-F stretching vibration. Results from this study show that the HFC global atmospheric lifetimes and REs are dependent upon their H atom content and molecular structure. Therefore, the HFC radiative metric evaluation requires a case-by-case evaluation. A thorough experimental evaluation of a targeted HFC's atmospheric lifetime and climate metrics is always highly recommended. However, in cases where it is experimentally difficult to separate isomers, the new results from this study should help guide the experiments, as well as provide relevant climate metrics with uncertainties and policy relevant data.

Changes in the quadriceps spinal reflex pathway after repeated sprint cycling are not influenced by ischemic preconditioning.

PURPOSE: We examined the effect of ischemic preconditioning (IPC) on changes in muscle force, activation, and the spinal reflex pathway during and after repeated sprint cycling. METHODS: Eight recreationally active men (high-intensity cardiorespiratory training > 3 times per week, > 6 months) completed two exercise sessions (5 sets of 5 cycling sprints, 150% max W), preceded by either IPC (3 × 5 min leg occlusions at 220 mmHg) or SHAM (3 × 5 min at 20 mmHg). Knee extensor maximal force and rate of force were measured before (PRE), immediately post (POST), 1H, and 24H after cycling. Twitch interpolation and resting potentiated twitches were applied to estimate voluntary activation and muscle contractility, respectively. Quadriceps H-reflex recruitment curves were collected at all time-points using 10 Hz doublet stimulation to allow estimation of H-reflex post-activation depression. Surface electromyograms and tissue oxygenation (via near-infrared spectroscopy) were continuously recorded during cycling. RESULTS: IPC did not affect any measure of neuromuscular function or performance during cycling. Maximal force and muscle contractility were significantly lower at POST and 1H compared to PRE and 24H by up to 50% (p < 0.01). Maximal force was lower than PRE at 24H by 8.7% (p = 0.028). Voluntary activation and rate of force were unchanged. A rightwards shift was observed for the H-reflex recruitment curve POST, and post-activation depression was higher than all other time-points at 24H (p < 0.05). Muscle activation and oxygenation decreased during cycling. CONCLUSIONS: IPC has a nominal effect on mechanisms associated with neuromuscular function during and after exercise in healthy populations.