Atg5 and Ambra1 differentially modulate neurogenesis in neural stem cells

Neuroepithelial cells undergoing differentiation efficiently remodel their cytoskeleton and shape in an energy-consuming process. The capacity of autophagy to recycle cellular components and provide energy could fulfill these requirements, thus supporting differentiation. However, little is known regarding the role of basal autophagy in neural differentiation. Here we report an increase in the expression of the autophagy genes Atg7, Becn1, Ambra1 and LC3 in vivo in the mouse embryonic olfactory bulb (OB) during the initial period of neuronal differentiation at E15.5, along with a parallel increase in neuronal markers. In addition, we observed an increase in LC3 lipidation and autophagic flux during neuronal differentiation in cultured OB-derived stem/progenitor cells. Pharmacological inhibition of autophagy with 3-MA or wortmannin markedly decreased neurogenesis. These observations were supported by similar findings in two autophagy-deficient genetic models. In Ambra1 loss-of-function homozygous mice (gt/gt) the expression of several neural markers was decreased in the OB at E13.5 in vivo. In vitro, Ambra1 haploinsufficient cells developed as small neurospheres with an impaired capacity for neuronal generation. The addition of methylpyruvate during stem/progenitor cell differentiation in culture largely reversed the inhibition of neurogenesis induced by either 3-MA or Ambra1 haploinsufficiency, suggesting that neural stem/progenitor cells activate autophagy to fulfill their high energy demands. Further supporting the role of autophagy for neuronal differentiation Atg5-null OB cells differentiating in culture displayed decreased TuJ1 levels and lower number of cells with neurites. These results reveal new roles for autophagy-related molecules Atg5 and Ambra1 during early neuronal differentiation of stem/progenitor cells

Pain Relief with Wet Cupping Theraphy in Rats is Mediated by Heat Shock Protein 70 and β-Endorphin

Background: Wet cupping therapy is a complementary therapy in pain management. The mechanism of this therapy, however, needs further elucidation. Cells injured by wet cupping therapy seem to stimulate the expression of heat shock protein 70 (HSP70). Its benefit in pain reduction could be mediated by the expression of ß-endorphin. This study aimed at determining the correlation between HSP70 and ß-endorphin after wet cupping therapy. Methods: Sixteen male Wistar rats were divided into control (CG; n=8) and treatment (TG; n=8) groups. The rats in both groups were injected with complete Freund’s adjuvant (CFA) at the footpad. In the TG, wet cupping therapy was done at the left and right paralumbar regions 48 hours after the CFA injection. Twenty-four hours after therapy, the hot plate test was done to assess pain threshold. Thereafter, immunohistochemistry from the skin subjected to wet cupping therapy was conducted for HSP70 and ß-endorphin. Results: The expression of HSP70 was significantly higher in the keratinocytes of the TG (20.25±3.53; P<0.001) than in the keratinocytes of the CG (10.50±2.44; P<0.001). The expression of ß-endorphin was significantly higher in the keratinocytes of the TG (22.37±3.52; P<0.001) than in the keratinocytes of the CG (5.12±1.72; P<0.001). The results also revealed a high correlation between HSP70 and ß-endorphin (β=0.864; P<0.001). Pain threshold after wet cupping therapy was significantly higher in the TG (22.81±6.34 s; P=0.003) than in the CG (11.78±3.56 s). Conclusions: The benefit of wet cupping therapy in terms of pain reduction in rats could be mediated by the expression of HSP70 and ß-endorphin

Arguments for F-theory

After a brief review of string and $M$-Theory we point out some deficiencies. Partly to cure them, we present several arguments for ``$F$-Theory'', enlarging spacetime to $(2, 10)$ signature, following the original suggestion of C. Vafa. We introduce a suggestive Supersymmetric 27-plet of particles, associated to the exceptional symmetric hermitian space $E_{6}/Spin^{c}(10)$. Several possible future directions, including using projective rather than metric geometry, are mentioned. We should emphasize that $F$-Theory is yet just a very provisional attempt, lacking clear dynamical principles.Comment: To appear in early 2006 in Mod. Phys. Lett. A as Brief Revie

Learning hydrodynamic equations for active matter from particle simulations and experiments

Recent advances in high-resolution imaging techniques and particle-based simulation methods have enabled the precise microscopic characterization of collective dynamics in various biological and engineered active matter systems. In parallel, data-driven algorithms for learning interpretable continuum models have shown promising potential for the recovery of underlying partial differential equations (PDEs) from continuum simulation data. By contrast, learning macroscopic hydrodynamic equations for active matter directly from experiments or particle simulations remains a major challenge. Here, we present a framework that leverages spectral basis representations and sparse regression algorithms to discover PDE models from microscopic simulation and experimental data, while incorporating the relevant physical symmetries. We illustrate the practical potential through applications to a chiral active particle model mimicking swimming cells and to recent microroller experiments. In both cases, our scheme learns hydrodynamic equations that reproduce quantitatively the self-organized collective dynamics observed in the simulations and experiments. This inference framework makes it possible to measure a large number of hydrodynamic parameters in parallel and directly from video data.Comment: Added statistical analysis of learned parameters, Added comparison to analytic coarse-graining approaches, Added spectral comparisons, Added framework application on fish dat

Kernel solutions of the Kostant operator on eight-dimensional quotient spaces

After introducing the generators and irreducible representations of the ${\rm su}(5)$ and ${\rm so}(6)$ Lie algebras in terms of the Schwinger's scillators, the general kernel solutions of the Kostant operators on eight-dimensional quotient spaces ${\rm su}(5)/{\rm su}(4)\times {\rm u}(1)$ and ${\rm so}(6)/{\rm so}(4)\times {\rm so}(2)$ are derived in terms of the diagonal subalgebras ${\rm su}(4)\times {\rm u}(1)$ and ${\rm so}(4)\times {\rm so}(2)$, respectively.Comment: 13 pages. Typos correcte

Interferon alfa subtypes and levels of type I interferons in the liver and peripheral mononuclear cells in patients with chronic hepatitis C and controls

Viral infections stimulate the transcription of interferon type I, which includes IFN-alfa (IFN-alpha) (13 subtypes) and IFN-beta (a single substance). Hepatitis C virus (HCV) infection is remarkable by its ability to evade host antiviral defenses; however, there is little information as to whether endogenous IFN is activated or not in this disease. Additionally, despite the fact that the various IFN-alpha subtypes may differ in biological activity, there are no data concerning the IFN-alpha subtypes specifically expressed in normal and diseased liver tissue. Thus, we have analyzed the IFN-alpha subtypes and the mRNA levels of type I IFNs in samples of normal liver tissue and in liver from patients with chronic hepatitis C. Similar studies were performed in peripheral blood mononuclear cells (PBMC) from patients and controls. After amplification and cloning of IFN-alpha cDNA, we observed that 98 of the 100 clones from normal liver tissue corresponded to the IFN-alpha5 subtype. However, in livers with chronic hepatitis C and in PBMC from controls and patients, a variety of subtypes, in addition to IFN-alpha5, were detected, suggesting a participation of infiltrating leukocytes in the production of IFN-alpha in livers with chronic hepatitis C. As compared with controls, patients with chronic hepatitis C showed a significant increase in IFN-beta mRNA in both the liver and PBMC, while IFN-alpha mRNA was significantly increased in PBMC but markedly reduced in liver tissue. In conclusion, IFN-alpha5 is the sole IFN-alpha subtype expressed in normal liver tissue. The hepatic levels of IFN-alpha are reduced in chronic hepatitis C, an event that may favor viral persistence

SYNTHESIS, CHARACTERIZATION AND ANTI-INFLAMMATORY ACTIVITY OF NOVEL PYRAZOLE DERIVATIVES

Objectives: To synthesize novel pyrazole derivatives and their evaluation for anti-inflammatory activity. Methods: The synthesis of chalcone (1) was carried out by using Claisen-Schmidt condensation. which on further cyclization with thiosemicarbazidegives the substituted 3, 5-diphenyl-4, 5-dihydro-pyrazole-1-carbothoic acid amide (2), further reaction with different aldehydes yield title compounds(3). Using this scheme 8 compounds were synthesized which further have been evaluated for anti-inflammatory activity by egg-albumin induced pawedema.Results: All the synthesized compounds have been supported by spectral analysis. The anti-inflammatory activity of synthesized compounds wascompared with standard anti-inflammatory agent Diclofenac sodium.Conclusion: Compound-8, compound-2 and compound-3 showed greater anti-inflammatory activity due to the presence of alkene and electronwithdrawing groups (Cl and NO2). Keywords: Chalcone, Thiosemicarbazide, Pyrazole derivatives, Anti-inflammatory activity

Quaternionic and Octonionic Spinors. A Classification

Quaternionic and octonionic realizations of Clifford algebras and spinors are classified and explicitly constructed in terms of recursive formulas. The most general free dynamics in arbitrary signature space-times for both quaternionic and octonionic spinors is presented. In the octonionic case we further provide a systematic list of results and tables expressing, e.g., the relations of the octonionic Clifford algebras with the $G_2$ cosets over the Lorentz algebras, the identities satisfied by the higher-rank antisymmetric octonionic tensors and so on. Applications of these results range from the classification of octonionic generalized supersymmetries, the construction of octonionic superstrings, as well as the investigations concerning the recently discovered octonionic $M$-superalgebra and its superconformal extension.Comment: 24 pages, LaTe

The Geometrodynamics of Sine-Gordon Solitons

The relationship between N-soliton solutions to the Euclidean sine-Gordon equation and Lorentzian black holes in Jackiw-Teitelboim dilaton gravity is investigated, with emphasis on the important role played by the dilaton in determining the black hole geometry. We show how an N-soliton solution can be used to construct ``sine-Gordon'' coordinates for a black hole of mass M, and construct the transformation to more standard ``Schwarzchild-like'' coordinates. For N=1 and 2, we find explicit closed form solutions to the dilaton equations of motion in soliton coordinates, and find the relationship between the soliton parameters and the black hole mass. Remarkably, the black hole mass is non-negative for arbitrary soliton parameters. In the one-soliton case the coordinates are shown to cover smoothly a region containing the whole interior of the black hole as well as a finite neighbourhood outside the horizon. A Hamiltonian analysis is performed for slicings that approach the soliton coordinates on the interior, and it is shown that there is no boundary contribution from the interior. Finally we speculate on the sine-Gordon solitonic origin of black hole statistical mechanics.Comment: Latex, uses epsf, 30 pages, 6 figures include