p38 Mapk signal pathway involved in anti-inflammatory effect of chaihu-shugan-san and shen-ling-bai-zhu-san on hepatocyte in non-alcoholic steatohepatitis rats

Background: Traditional Chinese Medicine (TCM), has over thousands-of-years history of use. Chaihu-Shugan-San (CSS), and Shen-ling-bai-zhu-San (SLBZS), are famous traditional Chinese herbal medicine formulas, which have been used in China, for the treatment of many chronic diseases.Materials and Methods:This study investigated the anti-inflammatory effects of CSS and SLBZS on signaling molecules involved in p38 mitogen-activated protein kinase (p38 MAPK), pathway on hepatocytes of non-alcoholic steatohepatitis (NASH), rats induced by high fat diet. SD male rats were randomly divided into 8 groups: negative control group, model control group, high (9.6g/kg/day)/low (3.2g/kg/day)-dose CSS group, high (30g/kg/day)/low (10g/kg/day)-dose SLBZS group, high (39.6g/kg/day)/low (13.2g/kg/day)-dose integrated group. The rats of NASH model were induced by feeding a high-fat diet. After 16, wks, Hepatocytes were isolated from 6, rats in each group by collagenase perfusion. The liver histopathological changes and serum inflammatory cytokines TNF-α, IL-6 were determined. The proteins of TLR4,  phosphor-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway were assayed.Results: The statistical data indicated the NASH model rats reproduced typical histopathological features of NASH in human. CSS and SLBZS ameliorated lipid metabolic disturbance, attenuated NASH progression, decreased the levels of TNF-α and IL-6 in serum, as well as inhibited TLR4 protein expression, p38 MAPK phosphorylation, and activation of p38 MAPK. In conclusion, CSS and SLBZS might work as a significant anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway.Conclusion: To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to protect against liver injury, alleviate the inflammation reaction, moderate NASH progression.Key words: p38 mitogen-activated protein kinase; Toll like receptor 4; Hepatocytes; Non-alcoholic Steatohepatitis; Traditional Chinese medicine

Ageing memory and glassiness of a driven vortex system

Many systems in nature, glasses, interfaces and fractures being some examples, cannot equilibrate with their environment, which gives rise to novel and surprising behaviour such as memory effects, ageing and nonlinear dynamics. Unlike their equilibrated counterparts, the dynamics of out-of- equilibrium systems is generally too complex to be captured by simple macroscopic laws. Here we investigate a system that straddles the boundary between glass and crystal: a Bragg glass formed by vortices in a superconductor. We find that the response to an applied force evolves according to a stretched exponential, with the exponent reflecting the deviation from equilibrium. After the force is removed, the system ages with time and its subsequent response time scales linearly with its age (simple ageing), meaning that older systems are slower than younger ones. We show that simple ageing can occur naturally in the presence of sufficient quenched disorder. Moreover, the hierarchical distribution of timescales, arising when chunks of loose vortices cannot move before trapped ones become dislodged, leads to a stretched-exponential response.Comment: 16 pages, 5 figure

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation

Direct Mediation and Metastable Supersymmetry Breaking for SO(10)

We examine a metastable $\mathcal{N}=1$ Macroscopic SO(N) SQCD model of Intriligator, Seiberg and Shih (ISS). We introduce various baryon and meson deformations, including multitrace operators and explore embedding an SO(10) parent of the standard model into two weakly gauged flavour sectors. Direct fundamental messengers and the symmetric pseudo-modulus messenger mediate SUSY breaking to the MSSM. Gaugino and sfermion masses are computed and compared for each deformation type. We also explore reducing the rank of the magnetic quark matrix of the ISS model and find an additional fundamental messenger.Comment: 43 pages, Latex. Version to appear in JHEP

Exceptional sperm cooperation in the wood mouse

Spermatozoa from a single male will compete for fertilization of ova with spermatozoa from another male when present in the female reproductive tract at the same time. Close genetic relatedness predisposes individuals towards altruism, and as haploid germ cells of an ejaculate will have genotypic similarity of 50%, it is predicted that spermatozoa may display cooperation and altruism to gain an advantage when inter-male sperm competition is intense. We report here the probable altruistic behaviour of spermatozoa in an eutherian mammal. Spermatozoa of the common wood mouse, Apodemus sylvaticus, displayed a unique morphological transformation resulting in cooperation in distinctive aggregations or 'trains' of hundreds or thousands of cells, which significantly increased sperm progressive motility. Eventual dispersal of sperm trains was associated with most of the spermatozoa undergoing a premature acrosome reaction. Cells undergoing an acrosome reaction in aggregations remote from the egg are altruistic in that they help sperm transport to the egg but compromise their own fertilizing ability

Wettability of amorphous and nanocrystalline Fe78B13Si9 substrates by molten Sn and Bi

The wettability of amorphous and annealing-induced nanocrystalline Fe78B13Si9 ribbons by molten Sn and Bi at 600 K was measured using an improved sessile drop method. The results demonstrate that the structural relaxation and crystallization in the amorphous substrates do not substantially change the wettability with molten Bi because of their invariable physical interaction, but remarkably deteriorate the wettability and interfacial bonding with molten Sn as a result of changing a chemical interaction to a physical one for the atoms at the interface

Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study

Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization

Revisiting the Hetero-Fertilization Phenomenon in Maize

Development of a seed DNA-based genotyping system for marker-assisted selection (MAS) has provided a novel opportunity for understanding aberrant reproductive phenomena such as hetero-fertilization (HF) by observing the mismatch of endosperm and leaf genotypes in monocot species. In contrast to conventional approaches using specific morphological markers, this approach can be used for any population derived from diverse parental genotypes. A large-scale experiment was implemented using seven F2 populations and four three-way cross populations, each with 534 to 1024 individuals. The frequency of HF within these populations ranged from 0.14% to 3.12%, with an average of 1.46%. The highest frequency of HF in both types of population was contributed by the pollen gametes. Using three-way crosses allowed, for the first time, detection of the HF contributed by maternal gametes, albeit at very low frequency (0.14%–0.65%). Four HF events identified from each of two F2 populations were tested and confirmed using 1032 single nucleotide polymorphic markers. This analysis indicated that only 50% of polymorphic markers can detect a known HF event, and thus the real HF frequency can be inferred by doubling the estimate obtained from using only one polymorphic marker. As expected, 99% of the HF events can be detected by using seven independent markers in combination. Although seed DNA-based analysis may wrongly predict plant genotypes due to the mismatch of endosperm and leaf DNA caused by HF, the relatively low HF frequencies revealed with diverse germplasm in this study indicates that the effect on the accuracy of MAS is limited. In addition, comparative endosperm and leaf DNA analysis of specific genetic stocks could be useful for revealing the relationships among various aberrant fertilization phenomena including haploidy and apomixis

Dirac Equation with Spin Symmetry for the Modified P\"oschl-Teller Potential in DD-dimensions

We present solutions of the Dirac equation with spin symmetry for vector and scalar modified P\"oschl-Teller potential within framework of an approximation of the centrifugal term. The relativistic energy spectrum is obtained using the Nikiforov-Uvarov method and the two-component spinor wavefunctions are obtain are in terms of the Jacobi polynomials. It is found that there exist only positive-energy states for bound states under spin symmetry, and the energy levels increase with the dimension and the potential range parameter $\alpha$.Comment: 9 pages and 1tabl

Dissociated Mechanisms of Extracting Perceptual Information into Visual Working Memory

The processing mechanisms of visual working memory (VWM) have been extensively explored in the recent decade. However, how the perceptual information is extracted into VWM remains largely unclear. The current study investigated this issue by testing whether the perceptual information was extracted into VWM via an integrated-object manner so that all the irrelevant information would be extracted (object hypothesis), or via a feature-based manner so that only the target-relevant information would be extracted (feature hypothesis), or via an analogous processing manner as that in visual perception (analogy hypothesis).High-discriminable information which is processed at the parallel stage of visual perception and fine-grained information which is processed via focal attention were selected as the representatives of perceptual information. The analogy hypothesis predicted that whereas high-discriminable information is extracted into VWM automatically, fine-grained information will be extracted only if it is task-relevant. By manipulating the information type of the irrelevant dimension in a change-detection task, we found that the performance was affected and the ERP component N270 was enhanced if a change between the probe and the memorized stimulus consisted of irrelevant high-discriminable information, but not if it consisted of irrelevant fine-grained information.We conclude that dissociated extraction mechanisms exist in VWM for information resolved via dissociated processes in visual perception (at least for the information tested in the current study), supporting the analogy hypothesis