Stationary solutions to a system of size-structured populations with nonlinear growth rate

We study stationary solutions to a system of size-structured population models with nonlinear growth rate. Several characterizations of stationary solutions are provided. It is shown that the steady-state problem can be converted into different problems such as two types of eigenvalue problems and a fixed-point problem. In the two-species case, we give an existence result of nonzero stationary solutions by using the fixed-point problem.     

Neovascular niche for human myeloma cells in immunodeficient mouse bone

The interaction with bone marrow (BM) plays a crucial role in pathophysiological features of multiple myeloma (MM), including cell proliferation, chemoresistance, and bone lesion progression. To characterize the MM-BM interactions, we utilized an in vivo experimental model for human MM in which a GFP-expressing human MM cell line is transplanted into NOG mice (the NOG-hMM model). Transplanted MM cells preferentially engrafted at the metaphyseal region of the BM endosteum and formed a complex with osteoblasts and osteoclasts. A subpopulation of MM cells expressed VE-cadherin after transplantation and formed endothelial-like structures in the BM. CD138(+) myeloma cells in the BM were reduced by p53-dependent apoptosis following administration of the nitrogen mustard derivative bendamustine to mice in the NOG-hMM model. Bendamustine maintained the osteoblast lining on the bone surface and protected extracellular matrix structures. Furthermore, bendamustine suppressed the growth of osteoclasts and mesenchymal cells in the NOG-hMM model. Since VE-cadherin(+) MM cells were chemoresistant, hypoxic, and HIF-2α-positive compared to the VE-cadherin(-) population, VE-cadherin induction might depend on the oxygenation status. The NOG-hMM model described here is a useful system to analyze the dynamics of MM pathophysiology, interactions of MM cells with other cellular compartments, and the utility of novel anti-MM therapies.     

Apology isn't good enough: an apology suppresses an approach motivation but not the physiological and psychological anger

Although studies have emphasized the multiple components of anger, little is known about the physiological and psychological mechanisms of the approach motivational component and the negative emotional component of anger. In the present study, participants wrote brief opinions about social problems (e.g., tuition hikes) and received a handwritten, insulting comment about their composition from the experimenter. Half of the participants (apology group) received a simple apologetic sentence at the end of the insulting comment. Half of the participants (no apology group) did not receive one. The physiological responses of the participants were recorded prior to, and after they read the comments. Increases in heart rate and asymmetric frontal brain activity were suppressed only in the apology group. Both groups showed an increase in skin conductance response. Our psychological scales showed that the apology suppressed self reported state anger from an approach-motivational standpoint but not from a negative emotional standpoint. The results suggest that anger is not a unitary process but has multiple components. The apology did provide a different physiological profile but did not dampen down the subjective experience of anger. Thus, providing an apology may not always be effective for alleviating the experience of anger to an insult.     

Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125

Vesicular stomatitis virus (VSV), a negative-sense single-stranded-RNA rhabdovirus, is an extremely promising oncolytic agent for cancer treatment. Since oncolytic virotherapy is moving closer to clinical application, potentially synergistic combinations of oncolytic viruses and molecularly targeted antitumor agents are becoming a meaningful strategy for cancer treatment. Mitogen-activated protein kinase (MAPK) inhibitors have been shown to impair liver cell proliferation and tumor development, suggesting their potential use as therapeutic agents for hepatocellular carcinoma (HCC). In this work, we show that the impairment of MAPK in vitro did not interfere with the oncolytic properties of VSV in HCC cell lines. Moreover, the administration of MAPK inhibitors did not restore the responsiveness of HCC cells to alpha/beta interferon (IFN-α/β). In contrast to previous reports, we show that JNK inhibition by the inhibitor SP600125 is not responsible for VSV attenuation in HCC cells and that this compound acts by causing a posttranslational modification of the viral glycoprotein.     

Local unfolding of Cu, Zn superoxide dismutase monomer determines the morphology of fibrillar aggregates

Aggregation of Cu, Zn superoxide dismutase (SOD1) is often found in amyotrophic lateral sclerosis patients. The fibrillar aggregates formed by wild type and various disease-associated mutants have recently been found to have distinct cores and morphologies. Previous computational and experimental studies of wild-type SOD1 suggest that the apo-monomer, highly aggregation prone, displays substantial local unfolding dynamics. The residual folded structure of locally unfolded apoSOD1 corresponds to peptide segments forming the aggregation core as identified by a combination of proteolysis and mass spectroscopy. Therefore, we hypothesize that the destabilization of apoSOD1 caused by various mutations leads to distinct local unfolding dynamics. The partially unfolded structure, exposing the hydrophobic core and backbone hydrogen bond donors and acceptors, is prone to aggregate. The peptide segments in the residual folded structures form the "building block" for aggregation, which in turn determines the morphology of the aggregates. To test this hypothesis, we apply a multiscale simulation approach to study the aggregation of three typical SOD1 variants: wild type, G37R, and I149T. Each of these SOD1 variants has distinct peptide segments forming the core structure and features different aggregate morphologies. We perform atomistic molecular dynamics simulations to study the conformational dynamics of apoSOD1 monomer and coarse-grained molecular dynamics simulations to study the aggregation of partially unfolded SOD1 monomers. Our computational studies of monomer local unfolding and the aggregation of different SOD1 variants are consistent with experiments, supporting the hypothesis of the formation of aggregation "building blocks" via apo-monomer local unfolding as the mechanism of SOD1 fibrillar aggregation.     

Responses to environmental stresses in woody plants: key to survive and longevity

Environmental stresses have adverse effects on plant growth and productivity, and are predicted to become more severe and widespread in decades to come. Especially, prolonged and repeated severe stresses affecting growth and development would bring down long-lasting effects in woody plants as a result of its long-term growth period. To counteract these effects, trees have evolved specific mechanisms for acclimation and tolerance to environmental stresses. Plant growth and development are regulated by the integration of many environmental and endogenous signals including plant hormones. Acclimation of land plants to environmental stresses is controlled by molecular cascades, also involving cross-talk with other stresses and plant hormone signaling mechanisms. This review focuses on recent studies on molecular mechanisms of abiotic stress responses in woody plants, functions of plant hormones in wood formation, and the interconnection of cell wall biosynthesis and the mechanisms shown above. Understanding of these mechanisms in depth should shed light on the factors for improvement of woody plants to overcome severe environmental stress conditions.     

Silicon and phosphorus linkage with iron via oxygen in the amorphous matrix of Gallionella ferruginea stalks

Bacterial species belonging to the genus Gallionella are Fe-oxidizing bacteria that produce uniquely twisted extracellular stalks consisting of iron-oxide-encrusted inorganic/organic fibers in aquatic environments. This paper describes the degree of crystallinity of Gallionella stalks and the chemical linkages of constituent elements in the stalk fibers. Transmission electron microscopy revealed that the matrix of the fiber edge consisted of an assembly of primary particles of approximately 3 nm in diameter. Scanning transmission electron microscopy revealed the rough granular surfaces of the fibers, which reflect the disordered assembly of the primary particles, indicating a high porosity and large specific surface area of the fibers. This may provide the surface with broader reactive properties. X-ray diffractometry, selected-area electron diffraction, and high-resolution transmission electron microscopy together showed that the primary particles had an amorphous structure. Furthermore, energy-dispersive X-ray analysis and Fourier transform infrared spectroscopy detected the bands characteristic of the vibrational modes assigned to O-H, Fe-O-H, P-O-H, Si-O-H, Si-O-Fe, and P-O-Fe bonds in the stalks, suggesting that the minor constituent elements P and Si could affect the degree of crystallinity of the fibers by linking with Fe via O. This knowledge about the mutual associations of these elements provides deeper insights into the unique inorganic/organic hybrid structure of the stalks.     

Pleiotropic Control of Secondary Metabolism and Morphological Development by KsbC,a Butyrolactone Autoregulator Receptor Homologue in Kitasatospora setae

The γ-butyrolactone autoregulator signaling cascades have been shown to control secondary metabolism and/or morphological development among many Streptomyces species. However, the conservation and variation of the regulatory systems among actinomycetes remain to be clarified. The genome sequence of Kitasatospora setae, which also belongs to the family Streptomycetaceae containing the genus Streptomyces, has revealed the presence of three homologues of the autoregulator receptor: KsbA, which has previously been confirmed to be involved only in secondary metabolism; KsbB; and KsbC. We describe here the characterization of ksbC, whose regulatory cluster closely resembles the Streptomyces virginiae barA locus responsible for the autoregulator signaling cascade. Deletion of the gene ksbC resulted in lowered production of bafilomycin and a defect of aerial mycelium formation, together with the early and enhanced production of a novel β-carboline alkaloid named kitasetaline. A putative kitasetaline biosynthetic gene cluster was identified, and its expression in a heterologous host led to the production of kitasetaline together with JBIR-133, the production of which is also detected in the ksbC disruptant, and JBIR-134 as novel β-carboline alkaloids, indicating that these genes were biosynthetic genes for β-carboline alkaloid and thus are the first such genes to be discovered in bacteria.     

MOCA is an integrator of the neuronal death signals that are activated by familial Alzheimer's disease-related mutants of amyloid β precursor protein and presenilins

The death of cholinergic neurons in the cerebral cortex and certain subcortical regions is linked to irreversible dementia relevant to AD (Alzheimer's disease). Although multiple studies have shown that expression of a FAD (familial AD)-linked APP (amyloid β precursor protein) or a PS (presenilin) mutant, but not that of wild-type APP or PS, induced neuronal death by activating intracellular death signals, it remains to be addressed how these signals are interrelated and what the key molecule involved in this process is. In the present study, we show that the PS1-mediated (or possibly the PS2-mediated) signal is essential for the APP-mediated death in a γ-secretase-independent manner and vice versa. MOCA (modifier of cell adhesion), which was originally identified as being a PS- and Rac1-binding protein, is a common downstream constituent of these neuronal death signals. Detailed molecular analysis indicates that MOCA is a key molecule of the AD-relevant neuronal death signals that links the PS-mediated death signal with the APP-mediated death signal at a point between Rac1 [or Cdc42 (cell division cycle 42)] and ASK1 (apoptosis signal-regulating kinase 1).     

Effects of antidepressants and mood stabilizers on serum levels of adiponectin

The effect of antidepressants and mood stabilizers on serum levels of adiponectin was investigated. Fluvoxamine (30 and 50?mg/kg/day) or lithium (40 and 60?mg/kg/day) was dissolved in distilled water and administered orally to rats every day for 4 weeks. Fluvoxamine (50 mg/kg/day) alone significantly elevated the serum level of adiponectin, but no significant difference was found between other drug-treated groups and the control group. This difference of these drugs' effectiveness on serum adiponectin might contribute to their differences of action mechanisms and therapeutic effects.