PERfect Day: reversible and dose-dependent control of circadian time-keeping in the mouse suprachiasmatic nucleus by translational switching of PERIOD2 protein expression.

The biological clock of the suprachiasmatic nucleus (SCN) orchestrates circadian (approximately daily) rhythms of behaviour and physiology that underpin health. SCN cell-autonomous time-keeping revolves around a transcriptional/translational feedback loop (TTFL) within which PERIOD (PER1,2) and CRYPTOCHROME (CRY1,2) proteins heterodimerise and suppress trans-activation of their encoding genes (Per1,2; Cry1,2). To explore its contribution to SCN time-keeping, we used adeno-associated virus-mediated translational switching to express PER2 (tsPER2) in organotypic SCN slices carrying bioluminescent TTFL circadian reporters.

Modulating NLRP3 splicing with antisense oligonucleotides to control pathological inflammation.

Inflammation has an essential role in healing. However, over-active inflammation disrupts normal cellular functions and can be life-threatening when not resolved. The NLRP3 inflammasome, a component of the innate immune system, is an intracellular multiprotein complex that senses stress-associated signals, and, for this reason is a promising therapeutic target for treating unresolved, pathogenic inflammation.

Elevating microRNA levels by targeting biogenesis with steric-blocking antisense oligonucleotides.

MicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric-blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs.

Multiharmonic Spanning Nonlinear X-wave: An Asymptotic State of Extreme Long Wave Infrared Dispersive Shock Regularization.

We predict the emergence of novel X-waves emitted as a consequence of extreme dispersive shock regularization of an intense long wave few cycle pulse propagating through a weakly dispersive medium. This robust propagation-invariant solution to Maxwell's equations appears as the asymptotic state in the high harmonic conversion when the pump propagates in a strongly nonlinear weakly dispersive regime, while the weakly nonlinear conical emission is dominated by chromatic dispersion.

Cardiac aging: from hallmarks to therapeutic opportunities.

Cardiac aging is an intricate and multifaceted process with considerable impact on public health, especially given the global demographic shift towards aged populations. This review discusses structural, cellular and functional changes associated with cardiac aging and heart failure with preserved ejection fraction (HFpEF). Key molecular mediators are considered within the framework of the established hallmarks of aging, with particular attention to promising therapeutic candidates.

Use of computed tomography to identify muscle quality subgroups, spatial mapping, and preliminary relationships to function in those with diabetic peripheral neuropathy.

Background: Decreased muscle volume and increased muscle-associated adipose tissue (MAAT, sum of intra and inter-muscular adipose tissue) of the foot intrinsic muscle compartment are associated with deformity, decreased function, and increased risk of ulceration and amputation in those with diabetic peripheral neuropathy (DPN).

Research Question: What is the muscle quality (normal, abnormal muscle, and adipose volumes) of the DPN foot intrinsic compartment, how does it change over time, and is muscle quality related to gait and foot function?

Methods: Computed tomography was performed on the intrinsic foot muscle compartment of 45 subjects with DPN (mean age: 67.2 ± 6.

Solid Phase Extraction Methodology for Robust Isotope Analysis of Atmospheric Ammonium.

The stable nitrogen isotope composition (δN) of atmospheric ammonia (NH) and ammonium (NH) has emerged as a potent tool for improving our understanding of the atmospheric burden of reduced nitrogen. However, current chemical oxidation methodologies commonly utilized for characterizing δN values of NH samples have been found to lead to low precision for low concentration (i.e.

Achilles tendon assessment on quantitative MRI: Sources of variability and relationships to tendinopathy.

Quantitative MRI (qMRI) measures are useful in assessing musculoskeletal tissues, but application to tendon has been limited. The purposes of this study were to optimize, identify sources of variability, and establish reproducibility of qMRI to assess Achilles tendon. Additionally, preliminarily estimates of effect of tendon pathology on qMRI metrics and structure-function relationships between qMRI measures and ankle performance were examined.

Nitrogen isotopic characteristics of aerosol ammonium in a Chinese megacity indicate the reduction from vehicle emissions during the lockdown period.

The role of agricultural versus vehicle emissions in urban atmospheric ammonia (NH) remains unclear. The lockdown due to the outbreak of COVID-19 provided an opportunity to assess the role of source emissions on urban NH. Concentrations and δN of aerosol ammonium (NH) were measured before (autumn in 2017) and during the lockdown (summer, autumn, and winter in 2020), and source contributions were quantified using SIAR.

The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward.

It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments in the field was published in the . Here, we explore new mechanisms and concepts that have emerged in the subsequent 25 years. Since 1997, methodological developments, such as luminescent and fluorescent reporter techniques, have revealed intricate relationships between cellular and network-level mechanisms.

miR-222 inhibits pathological cardiac hypertrophy and heart failure.

Aims: Physiological cardiac hypertrophy occurs in response to exercise and can protect against pathological stress. In contrast, pathological hypertrophy occurs in disease and often precedes heart failure. The cardiac pathways activated in physiological and pathological hypertrophy are largely distinct.

Correction: The circadian clock gene bmal1 is necessary for co-ordinated circatidal rhythms in the marine isopod Eurydice pulchra (Leach).

[This corrects the article DOI: 10.1371/journal.pgen.

Roles of Activin A and Gpnmb in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease [NAFLD]) and metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis [NASH]) are leading chronic liver diseases, driving cirrhosis, hepatocellular carcinoma, and mortality. MASLD/MASH is associated with increased senescence proteins, including Activin A, and senolytics have been proposed as a therapeutic approach. To test the role of Activin A, we induced hepatic expression of Activin A in a murine MASLD/MASH model.

Triple oxygen stable isotope analysis of nitrite measured using continuous flow isotope ratio mass spectrometry.

Oxygen stable isotopes (i.e., O, O, O) of nitrite (NO) are useful for investigating chemical processes and sources contributing to this important environmental contaminant and nutrient.

The circadian clock gene bmal1 is necessary for co-ordinated circatidal rhythms in the marine isopod Eurydice pulchra (Leach).

Circadian clocks in terrestrial animals are encoded by molecular feedback loops involving the negative regulators PERIOD, TIMELESS or CRYPTOCHROME2 and positive transcription factors CLOCK and BMAL1/CYCLE. The molecular basis of circatidal (~12.4 hour) or other lunar-mediated cycles (~15 day, ~29 day), widely expressed in coastal organisms, is unknown.

Viral-like TLR3 induction of cytokine networks and α-synuclein are reduced by complement C3 blockade in mouse brain.

Inflammatory processes and mechanisms are of central importance in neurodegenerative diseases. In the brain, α-synucleinopathies such as Parkinson's disease (PD) and Lewy body dementia (LBD) show immune cytokine network activation and increased toll like receptor 3 (TLR3) levels for viral double-stranded RNA (dsRNA). Brain inflammatory reactions caused by TLR3 activation are also relevant to understand pathogenic cascades by viral SARS-CoV-2 infection causing post- COVID-19 brain-related syndromes.

Quantitative Assessment of Peripheral Oxidative Metabolism With a New Dynamic H MRI Technique: A Pilot Study in People With and Without Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium-contrast-free H method to assess mitochondrial function by measuring low-concentration metabolites. A CEST MRI-based technique may serve as a non-invasive proxy for assessing mitochondrial health.

Long-term trends in inorganic aerosol chemical composition and chemistry at an urban and rural site in the northeastern US.

Atmospheric nitrate and sulfate are major inorganic particulate matter components that impact human and ecosystem health and air quality. Over the last several decades, emissions of the precursor gases, nitrogen oxides (NO = NO + NO) and sulfur dioxide (SO), have dramatically decreased in the US in response to federal regulations. However, the response in concentrations of particulate nitrate (pNO) and sulfate (pSO) have not followed predictions due to complex non-linear chemistry feedbacks that may differ amongst environments (i.