ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet in male mice.

Glucocorticoids modulate glucose homeostasis, acting on metabolically active tissues such as liver, skeletal muscle, and adipose tissue. Intracellular regulation of glucocorticoid action in adipose tissue impacts metabolic responses to obesity. ATP-binding cassette family C member 1 (ABCC1) is a transmembrane glucocorticoid transporter known to limit the accumulation of exogenously administered corticosterone in adipose tissue.

Psychedelics and Evidence-based Psychotherapy: A Systematic Review with Recommendations for Advancing Psychedelic Therapy Research.

Administration of psychedelics for mental health treatment, typically referred to as "psychedelic-assisted therapy," is a broad term with a very heterogeneous implementation. Despite increasing interest in the clinical application of psychedelic compounds for psychiatric disorders, there is no consensus on how to best integrate the psychedelic experience with evidence-based psychotherapeutic treatment. This systematic review provides a timely appraisal of existing approaches to combining psychotherapy with psychedelics and provides clear recommendations to best develop, optimize, and integrate evidence-based psychotherapy with psychedelic administration for straightforward scientific inference and maximal therapeutic benefit.

Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex.

Increasing evidence suggests synaptic dysfunction is a central and possibly triggering factor in Amyotrophic Lateral Sclerosis (ALS). Despite this, we still know very little about the molecular profile of an ALS synapse. To address this gap, we designed a synaptic proteomics experiment to perform an unbiased assessment of the synaptic proteome in the ALS brain.

An Optimized Comparative Proteomic Approach as a Tool in Neurodegenerative Disease Research.

Recent advances in proteomic technologies now allow unparalleled assessment of the molecular composition of a wide range of sample types. However, the application of such technologies and techniques should not be undertaken lightly. Here, we describe why the design of a proteomics experiment itself is only the first step in yielding high-quality, translatable results.

The Proteome Signatures of Fibroblasts from Patients with Severe, Intermediate and Mild Spinal Muscular Atrophy Show Limited Overlap.

Most research to characterise the molecular consequences of spinal muscular atrophy (SMA) has focused on SMA I. Here, proteomic profiling of skin fibroblasts from severe (SMA I), intermediate (SMA II), and mild (SMA III) patients, alongside age-matched controls, was conducted using SWATH mass spectrometry analysis. Differentially expressed proteomic profiles showed limited overlap across each SMA type, and variability was greatest within SMA II fibroblasts, which was not explained by copy number.

Motor unit recovery following Smn restoration in mouse models of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a childhood motor neuron disease caused by anomalies in the SMN1 gene. Although therapeutics have been approved for the treatment of SMA, there is a therapeutic time window, after which efficacy is reduced. Hallmarks of motor unit pathology in SMA include loss of motor-neurons and neuromuscular junction (NMJs).

The mitochondrial protein Sideroflexin 3 (SFXN3) influences neurodegeneration pathways in vivo.

Synapses are a primary pathological target in neurodegenerative diseases. Identifying therapeutic targets at the synapse could delay progression of numerous conditions. The mitochondrial protein SFXN3 is a neuronally enriched protein expressed in synaptic terminals and regulated by key synaptic proteins, including α-synuclein.

Temporal Profiling of the Cortical Synaptic Mitochondrial Proteome Identifies Ageing Associated Regulators of Stability.

Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology.

Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease.

CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons.

Pre-natal manifestation of systemic developmental abnormalities in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed a limited therapeutic time window and systemic aspects of the disease. This raises a fundamental question of whether SMA has presymptomatic, developmental components to disease pathogenesis.

Applying modern Omic technologies to the Neuronal Ceroid Lipofuscinoses.

The Neuronal Ceroid Lipofuscinoses are a group of severe and progressive neurodegenerative disorders, which generally present during childhood. With new treatments emerging on the horizon, there is a growing need to understand the specific disease mechanisms as well as identify prospective biomarkers for use to stratify patients and monitor treatment. The use of Omics technologies to NCLs has the potential to address this need.

Altered mitochondrial bioenergetics are responsible for the delay in Wallerian degeneration observed in neonatal mice.

Neurodegenerative and neuromuscular disorders can manifest throughout the lifespan of an individual, from infant to elderly individuals. Axonal and synaptic degeneration are early and critical elements of nearly all human neurodegenerative diseases and neural injury, however the molecular mechanisms which regulate this process are yet to be fully elucidated. Furthermore, how the molecular mechanisms governing degeneration are impacted by the age of the individual is poorly understood.

Selective vulnerability in neuronal populations in nmd/SMARD1 mice.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease causing distal limb muscle atrophy that progresses proximally and is accompanied by diaphragmatic paralysis. Neuromuscular junction (NMJ) alterations have been reported in muscles of SMARD1 model mice, known as nmd mice, with varying degrees of severity, suggesting that different muscles are specifically and selectively resistant or susceptible to denervation. To evaluate the extent of NMJ pathology in a broad range of muscles, a panel of axial and appendicular muscles were isolated and immunostained from nmd mice.

Quantitative imaging of tissue sections using infrared scanning technology.

Quantification of immunohistochemically (IHC) labelled tissue sections typically yields semi-quantitative results. Visualising infrared (IR) 'tags', with an appropriate scanner, provides an alternative system where the linear nature of the IR fluorophore emittance enables realistic quantitative fluorescence IHC (QFIHC). Importantly, this new technology enables entire tissue sections to be scanned, allowing accurate area and protein abundance measurements to be calculated from rapidly acquired images.

The association between remarriage and HIV infection in 13 sub-Saharan African countries.

Separated, divorced, and widowed individuals in Africa are at significantly increased risk for HIV infection. Using nationally representative data from 13 sub-Saharan African countries, this study confirms that finding and goes further by examining those who have experienced a marital dissolution and are now remarried. Results show that remarried individuals form a large portion of the population and have a higher-than-average HIV prevalence.

Variations in condom use by type of partner in 13 sub-Saharan African countries.

Using nationally representative data from 13 sub-Saharan African countries, we reinforce and expand upon previous findings that men report using condoms more frequently than women do and that unmarried respondents report that they use condoms with casual partners more frequently than married individuals report using them with their spouses. Based on descriptive, bivariate, and multivariate analyses, we also demonstrate to a degree not previously shown in the current literature that married men from most countries report using condoms with extramarital partners about as frequently as unmarried men report using them with casual partners. Married women from most of the countries included in the study reported using condoms with extramarital partners less frequently than unmarried women reported using them with casual partners.