Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice.

Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects.

Dipolar Order Induced Electron Spin Hyperpolarization.

The structure of coupled electron spin systems is of fundamental interest to many applications, including dynamic nuclear polarization (DNP), enhanced nuclear magnetic resonance (NMR), the generation of electron spin qubits for quantum information science (QIS), and quantitative studies of paramagnetic systems by electron paramagnetic resonance (EPR). However, the characterization of electron spin coupling networks is nontrivial, especially at high magnetic fields. This study focuses on a system containing high concentrations of trityl radicals that give rise to a DNP enhancement profile of H NMR characteristic of the presence of electron spin clusters.

Captivity affects mitochondrial aerobic respiration and carotenoid metabolism in the house finch (Haemorhous mexicanus).

In many species of animals, red carotenoid-based coloration is produced by metabolizing yellow dietary pigments, and this red ornamentation can be an honest signal of individual quality. However, the physiological basis for associations between organism function and the metabolism of red ornamental carotenoids from yellow dietary carotenoids remains uncertain. A recent hypothesis posits that carotenoid metabolism depends on mitochondrial performance, with diminished red coloration resulting from altered mitochondrial aerobic respiration.

P1 Center Electron Spin Clusters Are Prevalent in Type Ib Diamonds.

Understanding the spatial distribution of the P1 centers is crucial for diamond-based sensors and quantum devices. P1 centers serve as polarization sources for dynamic nuclear polarization (DNP) quantum sensing and play a significant role in the relaxation of nitrogen vacancy (NV) centers. Additionally, the distribution of NV centers correlates with the distribution of P1 centers, as NV centers are formed through the conversion of P1 centers.

Decarboxylative Iodination and Suzuki-Miyaura Coupling Reactions to Access Chiral 3,3'-Diaryl-1,1'-bi-2-naphthols.

An efficient synthesis of the enantiomerically pure 3,3'-bis-arylated BINOLs is accomplished through decarboxylative iodination of the dimethyl ether derivative of BINOL-3,3'-dicarboxylic acid followed by Suzuki-Miyaura coupling using a one-pot protocol. The decarboxylative iodination is effected with the dimethyl ether derivative of BINOL-3,3'-dicarboxylic acid using iodine as a terminal oxidant and the cheaply available KPO as a base under neat conditions. This protocol facilitated the introduction of the aryl group at the 3,3'-position on the binaphthyl system using aryl boronic acid through a palladium-catalyzed Suzuki-Miyaura coupling reaction.

Large Room Temperature Bulk DNP of C via P1 Centers in Diamond.

We use microwave-induced dynamic nuclear polarization (DNP) of the substitutional nitrogen defects (P1 centers) in diamond to hyperpolarize bulk C nuclei in both single crystal and powder samples at room temperature at 3.34 T. The large (>100-fold) enhancements demonstrated correspond to a greater than 10 000-fold improvement in terms of signal averaging of the 1% abundant C spins.

Room temperature DNP of diamond powder using frequency modulation.

Dynamic nuclear polarization (DNP) is a method of enhancing NMR signals via the transfer of polarization from electron spins to nuclear spins using microwave (MW) irradiation. In most cases, monochromatic continuous-wave (MCW) MW irradiation is used. Recently, several groups have shown that frequency modulation of the MW irradiation can result in an additional increase in DNP enhancement above that obtained with MCW.

Multi-Tissue Time-Domain NMR Metabolomics Investigation of Time-Restricted Feeding in Male and Female Nile Grass Rats.

Metabolic disease resulting from overnutrition is prevalent and rapidly increasing in incidence in modern society. Time restricted feeding (TRF) dietary regimens have recently shown promise in attenuating some of the negative metabolic effects associated with chronic nutrient stress. The purpose of this study is to utilize a multi-tissue metabolomics approach using nuclear magnetic resonance (NMR) spectroscopy to investigate TRF and sex-specific effects of high-fat diet in a diurnal Nile grass rat model.

Naked mole-rat and Damaraland mole-rat exhibit lower respiration in mitochondria, cellular and organismal levels.

Naked mole-rats (NMR) and Damaraland mole-rats (DMR) exhibit extraordinary longevity for their body size, high tolerance to hypoxia and oxidative stress and high reproductive output; these collectively defy the concept that life-history traits should be negatively correlated. However, when life-history traits share similar underlying physiological mechanisms, these may be positively associated with each other. We propose that one such potential common mechanism might be the bioenergetic properties of mole-rats.

Early Time-Restricted Feeding Amends Circadian Clock Function and Improves Metabolic Health in Male and Female Nile Grass Rats.

Lengthening the daily eating period contributes to the onset of obesity and metabolic syndrome. Dietary approaches, including energy restriction and time-restricted feeding, are promising methods to combat metabolic disorders. This study explored the effect of early and late time-restricted feeding (TRF) on weight and adiposity, food consumption, glycemic control, clock gene expression, and liver metabolite composition in diurnal Nile grass rats (NGRs).

Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain.

As a redox-sensitive coenzyme, nicotinamide adenine dinucleotide (NAD) plays a central role in cellular energy metabolism and homeostasis. Low NAD levels are linked to multiple disease states, including age-related diseases, such as metabolic and neurodegenerative diseases. Consequently, restoring/increasing NAD levels in vivo has emerged as an important intervention targeting age-related neurodegenerative diseases.

A Useful and Sustainable Role for N-of-1 Trials in the Healthcare Ecosystem.

Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient.

NaHSO/SiO catalyzed generation of -quinone/ -thioquinone methides: synthesis of arylxanthenes/ arylthioxanthenes oxa-6π-electrocyclization.

ortho-Quinone methides, very reactive transient intermediates, are utilized successfully in synthesizing complex organic molecules of natural and biological significance. Among several synthetic protocols, the acid catalyzed generation of ortho-quinone methides from suitably substituted phenols is a promising method for further exploitation in organic synthesis. Such an interesting reactive species is conveniently employed in the synthesis of conformationally restricted triarylmethane derivatives such as 12/9-arylxanthenes/arylthioxanthenes starting from symmetrical/unsymmetrical 2-(hydroxydiarylmethyl)phenol/thiophenol, respectively, using SiO2-NaHSO4.

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle.

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment-resistant depressed patients-one of several targets under investigation-has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself.

Medial forebrain bundle DBS differentially modulates dopamine release in the nucleus accumbens in a rodent model of depression.

Background: Medial forebrain bundle (MFB) deep brain stimulation (DBS) has anti-depressant effects clinically and in depression models. Currently, therapeutic mechanisms of MFB DBS or how stimulation parameters acutely impact neurotransmitter release, particularly dopamine, are unknown. Experimentally, MFB DBS has been shown to evoke dopamine response in healthy controls, but not yet in a rodent model of depression.

Hyperpolarized relaxometry based nuclear T noise spectroscopy in diamond.

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T).

Emergent Prethermalization Signatures in Out-of-Time Ordered Correlations.

How a many-body quantum system thermalizes-or fails to do so-under its own interaction is a fundamental yet elusive concept. Here we demonstrate nuclear magnetic resonance observation of the emergence of prethermalization by measuring out-of-time ordered correlations. We exploit Hamiltonian engineering techniques to tune the strength of spin-spin interactions and of a transverse magnetic field in a spin chain system, as well as to invert the Hamiltonian sign to reveal out-of-time ordered correlations.

The NRON complex controls circadian clock function through regulated PER and CRY nuclear translocation.

Post-translational regulation plays a central role in the circadian clock mechanism. However, nucleocytoplasmic translocation of core clock proteins, a key step in circadian timekeeping, is not fully understood. Earlier we found that the NRON scaffolding complex regulates nuclear translocation of NFAT and its signaling.

DNP-NMR of surface hydrogen on silicon microparticles.

Dynamic nuclear polarization (DNP) enhanced nuclear magnetic resonance (NMR) offers a promising route to studying local atomic environments at the surface of both crystalline and amorphous materials. We take advantage of unpaired electrons due to defects close to the surface of the silicon microparticles to hyperpolarize adjacent H nuclei. At 3.

Crystal structure of 4,5,6,7,8,8-hexa-chloro-2-(3,4-di-meth-oxy-pheneth-yl)-3a,4,7,7a-tetra-hydro-1-4,7-methano-iso-indole-1,3(2)-dione [+solvent].

In the title compound, CHClNO [+solvent], the six-membered ring of the norbornene moiety adopts a boat conformation and the two five-membered rings have envelope conformations. The pyrrolidine ring makes a dihedral angle of 14.83 (12)° with the 3,4-di-meth-oxy-phenyl ring, which are attached to each other by an extended N-CH-CH-C bridge.

Enhanced dynamic nuclear polarization via swept microwave frequency combs.

Dynamic nuclear polarization (DNP) has enabled enormous gains in magnetic resonance signals and led to vastly accelerated NMR/MRI imaging and spectroscopy. Unlike conventional -techniques, DNP methods that exploit the full electron spectrum are appealing since they allow direct participation of all electrons in the hyperpolarization process. Such methods typically entail sweeps of microwave radiation over the broad electron linewidth to excite DNP but are often inefficient because the sweeps, constrained by adiabaticity requirements, are slow.

mTOR signaling regulates central and peripheral circadian clock function.

The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN).

Developing Mammalian Cellular Clock Models Using Firefly Luciferase Reporter.

In mammals, many aspects of metabolic, physiological, and behavioral processes are regulated by endogenous circadian clocks. Oscillators of different tissue types share a common molecular mechanism at the cellular and molecular level which underlies the rhythmic expression of genes. Individual cells are the functional units for rhythm generation and cell-based clock models offer experimental tractability for discovery.

Exploring Localization in Nuclear Spin Chains.

Characterizing out-of-equilibrium many-body dynamics is a complex but crucial task for quantum applications and understanding fundamental phenomena. A central question is the role of localization in quenching thermalization in many-body systems and whether such localization survives in the presence of interactions. Probing this question in real systems necessitates the development of an experimentally measurable metric that can distinguish between different types of localization.