Mirrored Genome Size Distributions in Monocot and Dicot Plants

The variation in genome size and basic chromosome number was analyzed in the wide range of angiosperm plants. A divergence of monocots vs. dicots (eudicots) genome size distributions was revealed. A similar divergence was found for annual vs. perennial dicots. The divergence of monocots vs. dicots genome size distributions holds at different taxonomic levels and is more pronounced for species with larger genomes. Using nested analysis of variance, it was shown that putative constraints on genome size variation are not only stronger in dicots as compared to monocots but in the former they start to operate already at the family level, whereas in the latter they do so only at the order level. At the same time, variation in basic chromosome number is constrained at the order level in both groups. Higher basic chromosome numbers were found in perennial plants as compared to the annual ones, which can be explained by their need for a higher genetic recombination as compensation for the longer life-cycles. A negative correlation was found between genome size and basic chromosome number, which can be explained as a trade-off between different recombination mechanisms.     

Axonal Signals and Oligodendrocyte Differentiation

Axons produce signals that regulate oligodendrocyte proliferation, survival, terminal differentiation, and myelinogenesis. We review here recent in vitro and in vivo experimental approaches that aim to characterize axonal signals to oligodendroglia and to identify molecular mediators that regulate differentiation of oligodendendrocytes. We propose that the promoters of myelin genes, whose activation during terminal differentiation is modulated by axonal signals, can provide a means to identify molecular mediators of axo-oligodendroglial signals.     

Alterations in metabolism and gene expression in brain regions during cuprizone-induced demyelination and remyelination

Exposure of mice to the copper chelator, cuprizone, results in CNS demyelination. There is remyelination after removal of the metabolic insult. We present brain regional studies identifying corpus callosum as particularly severely affected; 65% of cerebroside is lost after 6 weeks of exposure. We examined recovery of cerebroside and ability to synthesize cerebroside and cholesterol following removal of the toxicant. The temporal pattern for concentration of myelin basic protein resembled that of cerebroside. We applied Affymetrix GeneChip technology to corpus callosum to identify temporal changes in levels of mRNAs during demyelination and remyelination. Genes coding for myelin structural components were greatly down-regulated during demyelination and up-regulated during remyelination. Genes related to microglia/macrophages appeared in a time-course (peaking at 6 weeks) correlating with phagocytosis of myelin and repair of lesions. mRNAs coding for many cytokines had peak expression at 4 weeks, compatible with intercellular signaling roles. Of interest were other genes with temporal patterns correlating with one of the three above patterns, but of function not obviously related to demyelination/remyelination. The ability to correlate gene expression with known pathophysiological events should help in elucidating further function of such genes as related to demyelination/remyelination.     

New principles of cell plasticity

Recent discoveries demonstrating surprising cell plasticity in animals and humans call into question many long held assumptions regarding differentiative potential of adult cells. These assumptions reflect a classical paradigm of cell lineage development projected onto both prenatal development and post-natal maintenance and repair of tissues. The classical paradigm describes unidirectional, hierarchical lineages proceedings step-wise from totipotent or pluripotent stem cells through intermediate, ever more restricted progenitor cells, leading finally to 'terminally differentiated' cells. However, in light of both the recent discoveries and older clinical or experimental findings, we have suggested principles comprising a new paradigm of cell plasticity, summarized here.     

Myelin basic protein component C1 in increasing concentrations can elicit fusion, aggregation, and fragmentation of myelin-like membranes

Myelin basic protein (MBP) is considered to have a primary role in the formation and maintenance of the myelin sheath. Many studies using artificial vesicle systems of simple lipid composition, and generally small size, have shown that MBP can elicit vesicle fusion, aggregation, or even fragmentation under different conditions. Here, we have studied the effects of increasing concentrations of bovine MBP charge isomer C1 (MBP/C1) on large unilamellar vesicles (LUVs) composed of phosphatidylcholine and phosphatidylserine (92:8 molar ratio), or with a lipid composition similar to that of the myelin membrane in vivo (Cyt-LUVs). Using absorbance spectrophotometry, fluorescence resonance energy transfer, dynamic light scattering and transmission electron microscopy, we have shown that vesicle aggregation and some vesicle fusion occurred upon addition of MBP/C1, and as the molar protein-lipid ratio increased. Fragmentation of Cyt-LUVs was observed at very high protein concentrations. These results showed that the phenomena of vesicle fusion, aggregation, and fragmentation can all be observed in one in vitro system, but were dependent on lipid composition and on the relative proportions of protein and lipid.     

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed.     

Knockdown of miR-210 decreases hypoxic glioma stem cells stemness and radioresistance

Glioma contains abundant hypoxic regions which provide niches to promote the maintenance and expansion of glioma stem cells (GSCs), which are resistant to conventional therapies and responsible for recurrence. Given the fact that miR-210 plays a vital role in cellular adaption to hypoxia and in stem cell survival and stemness maintenance, strategies correcting the aberrantly expressed miR-210 might open up a new therapeutic avenue to hypoxia GSCs. In the present study, to explore the possibility of miR-210 as an effective therapeutic target to hypoxic GSCs, we employed a lentiviral-mediated anti-sense miR-210 gene transfer technique to knockdown miR-210 expression and analyze phenotypic changes in hypoxic U87s and SHG44s cells. We found that hypoxia led to an increased HIF-2α mRNA expression and miR-210 expression in GSCs. Knockdown of miR-210 decreased neurosphere formation capacity, stem cell marker expression and cell viability, and induced differentiation and G0/G1 arrest in hypoxic GSCs by partially rescued Myc antagonist (MNT) protein expression. Knockdown of MNT could reverse the gene expression changes and the growth inhibition resulting from knockdown of miR-210 in hypoxic GSCs. Moreover, knockdown of miR-210 led to increased apoptotic rate and Caspase-3/7 activity and decreased invasive capacity, reactive oxygen species (ROS) and lactate production and radioresistance in hypoxic GSCs. These findings suggest that miR-210 might be a potential therapeutic target to eliminate GSCs located in hypoxic niches.     

Evidence of facultative daytime hypothermia in a small passerine wintering at northern latitudes

The use of hypothermia as a means to save energy is well documented in birds. This energy‐saving strategy is widely considered to occur exclusively at night in diurnally active species. However, recent studies suggest that facultative hypothermia may also occur during the day. Here, we document the use of daytime hypothermia in foraging Black‐capped Chickadees Poecile atricapillus wintering in eastern Canada. We measured the body temperature (T_b) of 126 individuals (plus 48 repeated measures) during a single winter and related values to ambient temperature (T_a) at the time of capture. We also tested whether daytime hypothermia was correlated with the size of body reserves (residuals of mass on structural size and fat score) and levels of metabolic performance (basal metabolic rate and maximum thermogenic capacity). We found that T_b of individual birds was lower when captured at low T_a, reaching values as low as 35.5 °C in actively foraging individuals. T_b was unrelated to metabolic performance or measures of body reserves. Therefore, daytime hypothermia does not result from individuals being unable to maintain T_b during cold spells or to a lack of body reserves. Our data also demonstrated a high level of individual variation in the depth of hypothermia, the causes of which remain to be explored.