Assessing the role of redox carriers in the reduction of CO by the oxo-acid: ferredoxin oxidoreductase superfamily.

The oxo-acid:ferredoxin oxidoreductase (OFOR) superfamily of enzymes are responsible for the reversible interconversion of CO and oxo-acids, using CoA-derivatives as co-substrates, and requiring redox equivalents in the form of a soluble redox-carrier protein ferredoxin (Fd). Ultimately, these enzymes are responsible for the reduction of CO to form pyruvate (in the case of PFOR) and oxo-glutarate (in the case of OGOR), by the reductive carboxylation reaction of acetyl-CoA and succinyl-CoA, respectively. The nature and kind of Fd that is the best redox-carrier to support the reductive reaction has been poorly studied to date.

Biophysical impact of sphingosine and other abnormal lipid accumulation in Niemann-Pick disease type C cell models.

Niemann-Pick disease type C (NPC) is a complex and rare pathology, which is mainly associated to mutations in the NPC1 gene. This disease is phenotypically characterized by the abnormal accumulation of multiple lipid species in the acidic compartments of the cell. Due to the complexity of stored material, a clear molecular mechanism explaining NPC pathophysiology is still not established.

Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling.

Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for decanoic acid, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system, , we show that decanoic acid can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1).

The Impact of Sleep Improvement on Food Choices in Adolescents With Late Bedtimes.

Purpose: The aim was to investigate the effect of sleep improvement on desire for and intake of weight gain-promoting foods in adolescents with late bedtimes.

Methods: A sample of 42 adolescents with late bedtimes was enrolled in an intervention designed to improve sleep. Their desire for and intake of food in the morning was assessed at before and after treatment.

Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function.

Abnormal accumulation of undigested macromolecules, often disease-specific, is a major feature of lysosomal and neurodegenerative disease and is frequently attributed to defective autophagy. The mechanistic underpinnings of the autophagy defects are the subject of intense research, which is aided by genetic disease models. To gain an improved understanding of the pathways regulating defective autophagy specifically in juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), a neurodegenerative disease of childhood, we developed and piloted a GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) screening assay to identify, in an unbiased fashion, genotype-sensitive small molecule autophagy modifiers, employing a JNCL neuronal cell model bearing the most common disease mutation in CLN3.

A rapid method for the preparation of ultrapure, functional lysosomes using functionalized superparamagnetic iron oxide nanoparticles.

Lysosomes are an emerging and increasingly important cellular organelle. With every passing year, more novel proteins and key cellular functions are associated with lysosomes. Despite this, the methodologies for their purification have largely remained unchanged since the days of their discovery.

Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: implications for atherosclerosis.

Vascular disease, such as atherosclerosis, is accompanied by changes in the mechanical properties of the vessel wall. Although altered mechanics is thought to contribute to disease progression, the molecular mechanisms whereby vessel wall stiffening could promote vascular occlusive disease remain unclear. It is well known that platelet-derived growth factor (PDGF) is a major stimulus for the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) and contributes critically to vascular disease.

Periprocedural MRI perfusion imaging to assess and monitor the hemodynamic impact of intracranial angioplasty and stenting for symptomatic atherosclerotic stenosis.

We aimed to assess the clinical value of MRI perfusion imaging in the periprocedural management of intracranial atherosclerosis, analyzing if changes in mean transit time (MTT), cerebral blood volume (CBV) and cerebral blood flow (CBF) correlated with angiographic outcomes. Pre-procedural and post-procedural MRI perfusion was performed on six patients who underwent angioplasty and/or stenting for symptomatic intracranial atherosclerosis. MTT, CBV and CBF were analyzed and graded.

Percutaneous vertebroplasty.

Vertebroplasty, the augmentation of vertebral compression fractures by image-controlled intracorporeal injection of polymethylmethacrylate cement, has shown a steady increase in use. Its chief indication is to palliate pain after a failure of noninvasive therapies. Other benefits include preventing further compression of the treated vertebra and fusing unstable fractures.