Loss of temporal coherence in the circadian metabolome across multiple tissues during ageing in mice.

Circadian clock function declines with ageing, which can aggravate ageing-related diseases such as type 2 diabetes and neurodegenerative disorders. Understanding age-related changes in the circadian system at a systemic level can contribute to the development of strategies to promote healthy ageing. The goal of this study was to investigate the impact of ageing on 24-h rhythms in amine metabolites across four tissues in young (2 months of age) and old (22-25 months of age) mice using a targeted metabolomics approach.

Small-molecule CEM3 strengthens single-cell oscillators in the suprachiasmatic nucleus.

A robust endogenous clock is required for proper function of many physiological processes. The suprachiasmatic nucleus (SCN) constitutes our central circadian clock and allows us to adapt to daily changes in the environment. Aging can cause a decline in the amplitude of circadian rhythms in SCN and peripheral clocks, which contributes to increased risk of several chronic diseases.

One seasonal clock fits all?

Adaptation of physiology and behavior to seasonal changes in the environment are for many organisms essential for survival. Most of our knowledge about the underlying mechanisms comes from research on photoperiodic regulation of reproduction in plants, insects and mammals. However, even humans, who mostly live in environments with minimal seasonal influences, show annual rhythms in physiology (e.

Measurement of Near-Field Radiative Heat Transfer at Deep Sub-Wavelength Distances using Nanomechanical Resonators.

Near-field radiative heat transfer (NFRHT) measurements often rely on custom microdevices that can be difficult to reproduce after their original demonstration. Here we study NFRHT using plain silicon nitride (SiN) membrane nanomechanical resonators─a widely available substrate used in applications such as electron microscopy and optomechanics─and on which other materials can easily be deposited. We report measurements down to a minimal distance of 180 nm between a large radius of curvature (15.

Reduced Plasticity in Coupling Strength in the Aging SCN Clock as Revealed by Kuramoto Modeling.

The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consists of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase coherence of the neurons is plastic and driven by the duration of daylight. With aging, the capacity to behaviorally adapt to seasonal changes in photoperiod reduces.

Aging affects GABAergic function and calcium homeostasis in the mammalian central clock.

Introduction: Aging impairs the function of the central circadian clock in mammals, the suprachiasmatic nucleus (SCN), leading to a reduction in the output signal. The weaker timing signal from the SCN results in a decline in rhythm strength in many physiological functions, including sleep-wake patterns. Accumulating evidence suggests that the reduced amplitude of the SCN signal is caused by a decreased synchrony among the SCN neurons.

Cleavage of an Aromatic C-C Bond in Ferrocene by Insertion of an Iridium Nitrido Nitrogen Atom.

The intermolecular cleavage of C-C bonds is a rare event. Herein, we report on a late transition-metal terminal nitrido complex, which upon oxidation undergoes insertion of the nitrido nitrogen atom into the aromatic C-C bond of ferrocene. This reaction path was confirmed through N and deuterium isotope labeling experiments of the nitrido complex and ferrocenium, respectively.

Single cell model for re-entrainment to a shifted light cycle.

Our daily 24-h rhythm is synchronized to the external light-dark cycle resulting from the Earth's daily rotation. In the mammalian brain, the suprachiasmatic nucleus (SCN) serves as the master clock and receives light-mediated input via the retinohypothalamic tract. Abrupt changes in the timing of the light-dark cycle (e.

Synthesis and reactivity of dinuclear copper(I) pyridine diimine complexes.

The reaction of a tethered pyridine diimine (PDI) ligand with copper(I) chloride yielded a μ-chlorido bridged cationic dicopper(I) PDI complex, which is a rare structural motif. The geometric constraint of the ligand is fostering attractive van der Waals interactions between the coplanar pyridine units. This is supported by an Atoms in Molecules (AIM) and NCI (non-covalent interaction) analysis.

Inhibitory responses to retinohypothalamic tract stimulation in the circadian clock of the diurnal rodent Rhabdomys pumilio.

In both diurnal and nocturnal mammals, the timing of activity is regulated by the central circadian clock of the suprachiasmatic nucleus (SCN). The SCN is synchronized to the external light cycle via the retinohypothalamic tract (RHT). To investigate potential differences in light processing between nocturnal mice and the diurnal rodent Rhabdomys pumilio, we mimicked retinal input by stimulation of the RHT ex vivo.

Induction of Fatigue by Specific Anthracycline Cancer Drugs through Disruption of the Circadian Pacemaker.

Cancer-related fatigue (CRF) is the most devastating long-term side effect of many cancer survivors that confounds the quality of life for months to years after treatment. However, the cause of CRF is poorly understood. As a result, cancer survivors, at best, receive psychological support.

Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue.

Lipid metabolism is under the control of the circadian system and circadian dysregulation has been linked to obesity and dyslipidemia. These factors and outcomes have also been associated to, or affected by, the process of aging. Here, we investigated whether murine white (WAT) and brown (BAT) adipose tissue lipids exhibit rhythmicity and if this is affected by aging.

A multi-level assessment of the bidirectional relationship between aging and the circadian clock.

The daily temporal order of physiological processes and behavior contribute to the wellbeing of many organisms including humans. The central circadian clock, which coordinates the timing within our body, is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Like in other parts of the brain, aging impairs the SCN function, which in turn promotes the development and progression of aging-related diseases.

Electrophysiological Approaches to Studying the Suprachiasmatic Nucleus.

In mammals, the part of the nervous system responsible for most circadian behavior can be localized to a bilaterally paired structure in the hypothalamus known as the suprachiasmatic nucleus (SCN). Understanding the mammalian circadian system will require a detailed multilevel analysis of neural SCN circuits ex vivo and in vivo. Many of the techniques and approaches that are used for the analysis of the circuitry driving circadian oscillations in the SCN are similar to those employed in other brain regions.

Brief light exposure at dawn and dusk can encode day-length in the neuronal network of the mammalian circadian pacemaker.

The central circadian pacemaker in mammals, the suprachiasmatic nucleus (SCN), is important for daily as well as seasonal rhythms. The SCN encodes seasonal changes in day length by adjusting phase distribution among oscillating neurons thereby shaping the output signal used for adaptation of physiology and behavior. It is well-established that brief light exposure at the beginning and end of the day, also referred to as "skeleton" light pulses, are sufficient to evoke the seasonal behavioral phenotype.

Aging Affects the Capacity of Photoperiodic Adaptation Downstream from the Central Molecular Clock.

Aging impairs circadian clock function, leading to disrupted sleep-wake patterns and a reduced capability to adapt to changes in environmental light conditions. This makes shift work or the changing of time zones challenging for the elderly and, importantly, is associated with the development of age-related diseases. However, it is unclear what levels of the clock machinery are affected by aging, which is relevant for the development of targeted interventions.

trans-Diastereoselective Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of α-Acetamido Benzocyclic Ketones via Dynamic Kinetic Resolution.

A highly efficient enantio- and diastereoselective catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution (DKR-ATH) of α,β-dehydro-α-acetamido and α-acetamido benzocyclic ketones to ent- trans-β-amido alcohols is disclosed employing a new ansa-Ru(II) complex of an enantiomerically pure syn- N, N-ligand, i.e. ent- syn-ULTAM-(CH)Ph.

Uncovering functional signature in neural systems via random matrix theory.

Neural systems are organized in a modular way, serving multiple functionalities. This multiplicity requires that both positive (e.g.

The influence of neuronal electrical activity on the mammalian central clock metabolome.

Introduction: Most organisms display circadian rhythms in physiology and behaviour. In mammals, these rhythms are orchestrated by the suprachiasmatic nucleus (SCN). Recently, several metabolites have emerged as important regulators of circadian timekeeping.

From clock to functional pacemaker.

In mammals, the central pacemaker that coordinates 24-hr rhythms is located in the suprachiasmatic nucleus (SCN). Individual neurons of the SCN have a molecular basis for rhythm generation and hence, they function as cell autonomous oscillators. Communication and synchronization among these neurons are crucial for obtaining a coherent rhythm at the population level, that can serve as a pace making signal for brain and body.

Effects of an intensive long-term prevention programme after myocardial infarction - a randomized trial.

Background: Long-term risk factor control after myocardial infarction (MI) is currently inadequate and there is an unmet need for effective secondary prevention programmes.

Design And Methods: It was the aim of the study to compare a 12-month intensive prevention programme (IPP), coordinated by prevention assistants and including education sessions, telephone visits and telemetric risk factor control, with usual care after MI. Three hundred and ten patients were randomized to IPP vs.

Differential Phase Arrangement of Cellular Clocks along the Tonotopic Axis of the Mouse Cochlea Ex Vivo.

Topological distributions of individual cellular clocks have not been demonstrated in peripheral organs. The cochlea displays circadian patterns of core clock gene expression [1, 2]. PER2 protein is expressed in the hair cells and spiral ganglion neurons of the cochlea in the spiral ganglion neurons [1].