Eukaryotic circadian clocks are built on transcriptional feedback loops. In mammals, the PERIOD (PER) and CRYPTOCHROME (CRY) proteins accumulate, form a large nuclear complex (PER complex), and ...repress their own transcription. We found that mouse PER complexes included RNA helicases DDX5 and DHX9, active RNA polymerase II large subunit, Per and Cry pre-mRNAs, and SETX, a helicase that promotes transcriptional termination. During circadian negative feedback, RNA polymerase II accumulated near termination sites on Per and Cry genes but not on control genes. Recruitment of PER complexes to the elongating polymerase at Per and Cry termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. Circadian clock negative feedback thus includes direct control of transcriptional termination.
The circadian clock of Neurospora crassa is based on a negative transcriptional/translational feedback loops. The frequency (frq) gene controls the morning-specific rhythmic transcription of a sense ...RNA encoding FRQ, the negative element of the core circadian feedback loop. In addition, a long noncoding antisense RNA, qrf, is rhythmically transcribed in an evening-specific manner. It has been reported that the qrf rhythm relies on transcriptional interference with frq transcription and that complete suppression of qrf transcription impairs the circadian clock. We show here that qrf transcription is dispensable for circadian clock function. Rather, the evening-specific transcriptional rhythm of qrf is mediated by the morning-specific repressor CSP-1. Since CSP-1 expression is induced by light and glucose, this suggests a rhythmic coordination of qrf transcription with metabolism. However, a possible physiological significance for the circadian clock remains unclear, as suitable assays are not available.
Emergency measures in the face of the recent COVID-19 pandemic have been different among countries, although most have opted for confinement and restrictions on social contact. These measures have ...generated lifestyle changes with potential effects on individuals' health. The disturbances in daily routines due to confinement and remote work have impacted circadian rhythms and energy balance; however, the consequences of these disruptions have not been studied in depth. The objective was to evaluate the impact of 12-week confinement on body weight, considering changes in several external synchronizers of the biological clock.
The participants, 521 university students (16–35 years), responded to 52 questions oriented to determine light exposure, sleep patterns, sedentary lifestyle, and eating times.
We found a reduction in sunlight exposure and sleep duration, an increment in sedentarism and screen exposure, and a delay in the timing of the main meals and sleep in the whole cohort. These behavioral changes were associated with a twofold increase in obesity. Subjects who increased their sedentary hours and shortened their sleep to a higher degree were those who gained more bodyweight. The most influential factors in body weight variation during confinement were sleep duration, physical activity (sedentarism), and light (timing of screen exposure). The mediation model explained 6% of the total body weight variation.
Results support a significant impact of confinement on several external synchronizers of the biological clock and on body weight. Health-related recommendations during the pandemic must include behavioral recommendations to mitigate the adverse effects on the biological clock.
Abstract
We present a new framework to study the time variation of fundamental constants in a model-independent way. Model independence implies more free parameters than assumed in previous studies. ...Using data from atomic clocks based on
87
Sr,
171
Yb
+
and
133
Cs, we set bounds on parameters controlling the variation of the fine-structure constant,
α
, and the electron-to-proton mass ratio,
µ
. We consider variations on timescales ranging from a minute to almost a day. In addition, we use our results to derive some of the tightest limits to date on the parameter space of models of ultralight dark matter and axion-like particles.
Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the ...pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1AVPV, and arcuate hypothalamus, Kiss1ARH), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons. The reproductive axis is primarily regulated by gonadal steroid and circadian cues, but the starvation-sensitive input that inhibits this circuit during negative energy balance remains controversial. Agouti-related peptide (AgRP)-expressing neurons are activated during starvation and have been implicated in leptin-associated infertility. To test whether these neurons relay information to the reproductive circuit, we used AgRP-neuron ablation and optogenetics to explore connectivity in acute slice preparations. Stimulation of AgRP fibers revealed direct, inhibitory synaptic connections with Kiss1ARH and Kiss1AVPV neurons. In agreement with this finding, Kiss1ARH neurons received less presynaptic inhibition in the absence of AgRP neurons (neonatal toxin-induced ablation). To determine whether enhancing the activity of AgRP neurons is sufficient to attenuate fertility in vivo, we artificially activated them over a sustained period and monitored fertility. Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and decreased fertility. These findings are consistent with the idea that, during metabolic deficiency, AgRP signaling contributes to infertility by inhibiting Kiss1 neurons.
The circadian clock coordinates the daily cyclic rhythm of numerous biological processes by regulating a large portion of the transcriptome. In animals, the circadian clock is involved in aging and ...senescence, and circadian disruption by mutations in clock genes frequently accelerates aging. Conversely, aging alters circadian rhythmicity, which causes age-associated physiological alterations. However, interactions between the circadian clock and aging have been rarely studied in plants. Here, we investigated potential roles for the circadian clock in the regulation of leaf senescence in plants. Members of the evening complex in Arabidopsis circadian clock, EARLY FLOWERING 3 (ELF3), EARLY FLOWERING 4 (ELF4), and LUX ARRHYTHMO (LUX), as well as the morning component PSEUDO-RESPONSE REGULATOR 9 (PRR9), affect both age-dependent and dark-induced leaf senescence. The circadian clock regulates the expression of several senescence-related transcription factors. In particular, PRR9 binds directly to the promoter of the positive aging regulator ORESARA1 (ORE1) gene to promote its expression. PRR9 also represses miR164, a posttranscriptional repressor of ORE1. Consistently, genetic analysis revealed that delayed leaf senescence of a prr9 mutant was rescued by ORE1 overexpression. Thus, PRR9, a core circadian component, is a key regulator of leaf senescence via positive regulation of ORE1 through a feed-forward pathway involving posttranscriptional regulation by miR164 and direct transcriptional regulation. Our results indicate that, in plants, the circadian clock and leaf senescence are intimately interwoven as are the clock and aging in animals.
Over the last years some interest has been gathered by f(Q) theories, which are new candidates to replace Einstein's prescription for gravity. The nonmetricity tensor Q allows to put forward the ...assumption of a free torsionless connection and, consequently, new degrees of freedom in the action are taken into account. This work focuses on a class of f(Q) theories, characterized by the presence of a general power-law term which adds up to the standard (linear in) Q term in the action, and on new cosmological scenarios arising from them. Using the Markov chain Monte Carlo method, we carry out statistical tests relying upon background data such as Type Ia supernovae luminosities and direct Hubble data (from cosmic clocks), along with cosmic microwave background shift and baryon acoustic oscillations data. This allows us to perform a multifaceted comparison between these new cosmologies and the (concordance) ΛCDM setup. We conclude that, at the current precision level, the best fits of our f(Q) models correspond to values of their specific parameters which make them hardly distinguishable from our general relativity "échantillon," that is, ΛCDM.
Clinical effects of transcranial electrical stimulation with weak currents are remarkable considering the low amplitude of the electric fields acting on the brain. Elucidating the processes by which ...small currents affect ongoing brain activity is of paramount importance for the rational design of noninvasive electrotherapeutic strategies and to determine the relevance of endogenous fields. We propose that in active neuronal networks, weak electrical fields induce small but coherent changes in the firing rate and timing of neuronal populations that can be magnified by dynamic network activity. Specifically, we show that carbachol-induced gamma oscillations (25-35 Hz) in rat hippocampal slices have an inherent rate-limiting dynamic and timing precision that govern susceptibility to low-frequency weak electric fields (<50 Hz; <10 V/m). This leads to a range of nonlinear responses, including the following: (1) asymmetric power modulation by DC fields resulting from balanced excitation and inhibition; (2) symmetric power modulation by lower frequency AC fields with a net-zero change in firing rate; and (3) half-harmonic oscillations for higher frequency AC fields resulting from increased spike timing precision. These underlying mechanisms were elucidated by slice experiments and a parsimonious computational network model of single-compartment spiking neurons responding to electric field stimulation with small incremental polarization. Intracellular recordings confirmed model predictions on neuronal timing and rate changes, as well as spike phase-entrainment resonance at 0.2 V/m. Finally, our data and mechanistic framework provide a functional role for endogenous electric fields, specifically illustrating that modulation of gamma oscillations during theta-modulated gamma activity can result from field effects alone.
Plants monitor day length and memorize changes in temperature signals throughout the day, creating circadian rhythms that support the timely control of physiological and metabolic processes. The
(
) ...transcription factors are known as master regulators for the acquisition of cold stress tolerance, whereas
(
) is involved in plant adaptation to heat stress through thermomorphogenesis. Recent studies have shown that circadian clock genes control plant responses to temperature. Temperature-responsive transcriptomes show a diurnal cycle and peak expression levels at specific times of throughout the day. Circadian clock genes play essential roles in allowing plants to maintain homeostasis by accommodating temperature changes within the normal temperature range or by altering protein properties and morphogenesis at the cellular level for plant survival and growth under temperature stress conditions. Recent studies revealed that the central oscillator genes
/
(
) and
/
/
(
/
/
), as well as the
(
) genes
(
/
), were involved in the
pathway of the cold signaling transcription factor and regulated the thermomorphogenesis gene
. Further studies showed that another central oscillator,
(
), and the regulatory protein
(
) are also involved. These studies led to attempts to utilize circadian clock genes for the acquisition of temperature-stress resistance in crops. In this review, we highlight circadian rhythm regulation and the clock genes involved in plant responses to temperature changes, as well as strategies for plant survival in a rapidly changing global climate.
Atomic clock frequency jumps directly influence the accuracy and reliability of timekeeping systems. The necessary corrections are typically implemented by postprocessing mutual comparison data ...between multiple atomic clocks based on the overly strict assumption that these atomic clocks are independent of each other. This paper describes the concept of a mirror clock, which enables atomic clock frequency jumps to be identified in real time without any assumptions. By comparing whether the real measured data and a corresponding mirror clock prediction fall within a confidence interval determined by the uncertainty of past physical clock data, atomic clock frequency jumps can be effectively identified and corrected. The results of several experiments using three hydrogen masers verify that the precision and recall of simultaneous jump identification reach 96.41% and 73.49%, respectively.
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