The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models

Recent research has shown that mtDNA-deficient cancer cells (ρ0 cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1KO) mice markedly delayed tumor formation after grafting ρ0 cancer cells. Miro1KO mice with fluorescently labeled mitochondria revealed that this delay was due to hindered mitochondrial transfer from the tumor stromal cells to grafted B16 ρ0 cells, which impeded recovery of mitochondrial respiration and tumor growth. Miro1KO led to the perinuclear accumulation of mitochondria and impaired mobility of the mitochondrial network. In vitro experiments revealed decreased association of mitochondria with microtubules, compromising mitochondrial transfer via tunneling nanotubes (TNTs) in mesenchymal stromal cells. Here we show the role of Miro1 in horizontal mitochondrial transfer in mouse melanoma models in vivo and its involvement with TNTs

Identifying Low pH Active and Lactate-Utilizing Taxa within Oral Microbiome Communities from Healthy Children Using Stable Isotope Probing Techniques

<div><h3>Background</h3><p>Many human microbial infectious diseases including dental caries are polymicrobial in nature. How these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral bacteria have been characterized <em>in vitro</em>, their physiology within the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these species remain uncultivated to date with little known besides their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated species will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for <em>in vitro</em> temporal monitoring of metabolites and identification of metabolically active and inactive bacterial species.</p> <h3>Methodology/Principal Findings</h3><p>Supragingival plaque samples from caries-free children incubated with ¹³C-substrates under imposed healthy (buffered, pH 7) and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic acid from glucose metabolism. Rapid lactate utilization upon glucose depletion was observed under pH 7 conditions. SIP analyses revealed a number of genera containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5. The diversity of active species decreased significantly at pH 4.5 and was dominated by <em>Lactobacillus</em> and <em>Propionibacterium</em> species, both of which have been previously found within carious lesions from children.</p> <h3>Conclusions/Significance</h3><p>Our approach allowed for identification of species that metabolize carbohydrates under different pH conditions and supports the importance of Lactobacilli and Propionibacterium in the development of childhood caries. Identification of species within healthy subjects that are active at low pH can lead to a better understanding of oral caries onset and generate appropriate targets for preventative measures in the early stages.</p> </div

The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity

Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls. Using a whole-cell competitive binding assay and H-3-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855+/-1389 sites/cell which was significantly lower (p0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport. (J. Endocrinol. Invest. 21: 656-661, 1998) (C)1998, Editrice Kurtis

Very Early Development of Nucleus Taeniae of the Amygdala

Ikebuchi M, Nanbu S, Okanoya K, Suzuki R, Bischof H-J. Very Early Development of Nucleus Taeniae of the Amygdala. Brain Behavior And Evolution. 2013;81(1):12-26.The avian nucleus taeniae of the amygdala (TnA) corresponds to part of the mammalian medial amygdala. Like its mammalian counterpart, it has been shown to be involved in the control of social function. According to behavioral observations, such control is already necessary early in the ontogenetic development of a bird. If so, TnA should be one of the earliest differentiating brain structures of the telencephalon. Our anatomical study shows that TnA can already be delineated at posthatching day one. The volume of TnA exhibits a growth spurt between days 1 and 8 posthatch, developing at a faster rate than the entire telencephalon. Our results suggest that between days 1 and 8 the growth of neuropil exceeds the enhancement of neuron number (leading to a decrease of cell density), and an addition at the same pace of new neurons and neuropil thereafter. A plateau is reached at posthatch day 30. The development of TnA precedes that of the song control nuclei and is similar to the early growth of thalamic and telencephalic sensory areas. This adds to the idea that this structure may already be involved in social control at the time of hatching. A proximate cause of the early development of TnA might be the direct afference from the olfactory bulb. Copyright (C) 2012 S. Karger AG, Base