Atomic force microscopy characterization of white and beige adipocyte differentiation.

Adipose tissue plays an essential role in systemic metabolism with white adipose tissue (WAT) making up most of the tissue and being involved in the regulation of energy homeostasis, and brown and beige adipose tissue (BAT) exhibiting thermogenic activity. There is promise in the conversion of white adipocytes into beige ones as a therapeutic potential to control and enhance systemic metabolism, but it is difficult to maintain this transformation in vivo because we do not fully understand the mechanism of conversion. In this study, we applied atomic force microscopy (AFM) to characterize beige or white adipocytes during the process of differentiation for morphology, roughness, adhesion, and elasticity at different time points.

Three-Dimensional Culture of Vascularized Thermogenic Adipose Tissue from Microvascular Fragments.

Engineering thermogenic adipose tissue (e.g., beige or brown adipose tissues) has been investigated as a potential therapy for metabolic diseases or for the design of personalized microtissues for health screening and drug testing.

CTB-targeted protocells enhance ability of lanthionine ketenamine analogs to induce autophagy in motor neuron-like cells.

Impaired autophagy, a cellular digestion process that eliminates proteins and damaged organelles, has been implicated in neurodegenerative diseases, including motor neuron disorders. Motor neuron targeted upregulation of autophagy may serve as a promising therapeutic approach. Lanthionine ketenamine (LK), an amino acid metabolite found in mammalian brain tissue, activates autophagy in neuronal cell lines.

Laminin-α4 Negatively Regulates Adipocyte Beiging Through the Suppression of AMPKα in Male Mice.

Laminin-α4 (LAMA4) is an extracellular matrix protein implicated in the regulation of adipocyte differentiation and function. Prior research describes a role for LAMA4 in modulating adipocyte thermogenesis and uncoupling protein-1 (UCP1) expression in white adipose; however, the mechanisms involved are poorly understood. Here, we describe that Lama4 knockout mice (Lama4-/-) exhibit heightened mitochondrial biogenesis and peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) expression in subcutaneous white adipose tissue (sWAT).

Engineering Human Beige Adipose Tissue.

In this study, we described a method for generating functional, beige (thermogenic) adipose microtissues from human microvascular fragments (MVFs). The MVFs were isolated from adipose tissue acquired from adults over 50 years of age. The tissues express thermogenic gene markers and reproduce functions essential for the potential therapeutic impact of beige adipose tissues such as enhanced lipid metabolism and increased mitochondrial respiration.

cytoNet: Spatiotemporal network analysis of cell communities.

We introduce cytoNet, a cloud-based tool to characterize cell populations from microscopy images. cytoNet quantifies spatial topology and functional relationships in cell communities using principles of network science. Capturing multicellular dynamics through graph features, cytoNet also evaluates the effect of cell-cell interactions on individual cell phenotypes.

Laminin-α4 Is Upregulated in Both Human and Murine Models of Obesity.

Obesity affects nearly one billion globally and can lead to life-threatening sequelae. Consequently, there is an urgent need for novel therapeutics. We have previously shown that laminin, alpha 4 () knockout in mice leads to resistance to adipose tissue accumulation; however, the relationship between and obesity in humans has not been established.

Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity.

Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited.

Developing Strategies for Sustainable Medical Equipment Maintenance in Under-Resourced Settings.

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics.

Diaphragm neuromuscular transmission failure in aged rats.

In aging Fischer 344 rats, phrenic motor neuron loss, neuromuscular junction abnormalities, and diaphragm muscle (DIAm) sarcopenia are present by 24 mo of age, with larger fast-twitch fatigue-intermediate (type FInt) and fast-twitch fatigable (type FF) motor units particularly vulnerable. We hypothesize that in old rats, DIAm neuromuscular transmission deficits are specific to type FInt and/or FF units. In phrenic nerve/DIAm preparations from rats at 6 and 24 mo of age, the phrenic nerve was supramaximally stimulated at 10, 40, or 75 Hz.

Frequency-dependent lipid raft uptake at rat diaphragm muscle axon terminals.

Introduction: In motor neurons, cholera toxin B (CTB) binds to the cell-surface ganglioside GM1 and is internalized and transported via structurally unique components of plasma membranes (lipid rafts).

Methods: Lipid raft uptake by axon terminals adjoining type-identified rat diaphragm muscle fibers was investigated using CTB and confocal imaging.

Results: Lipid raft uptake increased significantly at higher frequency stimulation (80 Hz), compared with lower frequency (20 Hz) and unstimulated (0 Hz) conditions.

Impaired Autophagy in Motor Neurons: A Final Common Mechanism of Injury and Death.

Autophagy is a cellular digestion process that contributes to cellular homeostasis and adaptation by the elimination of proteins and damaged organelles. Evidence suggests that dysregulation of autophagy plays a role in neurodegenerative diseases, including motor neuron disorders. Herein, we review emerging evidence indicating the roles of autophagy in physiological motor neuron processes and its function in specific compartments.

Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons.

Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis.

Motoneuron glutamatergic receptor expression following recovery from cervical spinal hemisection.

Cervical spinal hemisection at C2 (SH) removes premotor drive to phrenic motoneurons located in segments C3-C5 in rats. Spontaneous recovery of ipsilateral diaphragm muscle activity is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-D-aspartate (NMDA) receptors and decreased expression of α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors. Glutamatergic receptor expression is regulated by tropomyosin-related kinase receptor subtype B (TrkB) signaling in various neuronal systems, and increased TrkB receptor expression in phrenic motoneurons enhances recovery post-SH.

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells.

Background: Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions.

New Method: We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes.