Painlev\'e Analysis, Prelle-Singer Approach, Symmetries and Integrability of Damped H\'enon-Heiles System

We consider a modified damped version of H\'enon-Heiles system and investigate its integrability. By extending the Painlev\'e analysis of ordinary differential equations we find that the modified H\'enon-Heiles system possesses the Painlev\'e property for three distinct parametric restrictions. For each of the identified cases, we construct two independent integrals of motion using the well known Prelle-Singer method. We then derive a set of nontrivial non-point symmetries for each of the identified integrable cases of the modified H\'enon-Heiles system. We infer that the modified H\'enon-Heiles system is integrable for three distinct parametric restrictions. Exact solutions are given explicitly for two integrable cases.Comment: Accepted for publication in Journal of Mathematical Physic

Hypoxia and Extracellular Matrix Proteins Influence Angiogenesis and Lymphangiogenesis in Mouse Embryoid Bodies

Regulatory mechanisms for angiogenesis are relatively well established compared to lymphangiogenesis. Few studies have shown that a combination of vascular endothelial growth factor VEGF-A/C with hypoxia or collagen matrix promotes lymphatic structures along with blood vessel development in mouse embryoid bodies (EB). In this study we tested the hypothesis that while hypoxia combined with prolonged VEGF-A/C treatment would induce early lymphangiogenesis in addition to angiogenesis in mouse EBs, under similar conditions specific extracellular matrix (ECM) proteins would promote lymphatic vessel-like structures over angiogenesis. EBs were subjected to four conditions and were maintained under normoxia and hypoxia (21% and 2.6% O2, respectively) with or without VEGF-A/C. Microarray analyses of normoxic and hypoxic EBs, and immunofluorescence data showed very low expression of early lymphatic endothelial cell (LEC) markers, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), and prospero-related homeobox 1 (Prox1) at early time points. Double immunofluorescence using MECA-32 and Prox1/LYVE1 demonstrated that combined hypoxia and VEGF-A/C treatment promoted formation of blood vessel-like structures, whereas only Prox1+/LYVE1+ LECs were detected in EBs at E22.5. Furthermore, EBs were grown on laminin or collagen-I coated plates and were subjected to the four treatments as described above. Results revealed that LECs in EBs at E36.5 attached better to collagen-I, resulting in an organized network of lymphatic vessel-like structures as compared to EBs grown on laminin. However, blood vessel-like structures were less favored under these same conditions. Collectively, our data demonstrate that hypoxia combined with growth factors promotes angiogenesis, whereas combination of these conditions with specific ECM proteins favors lymphangiogenesis processes in mouse EBs

Photocatalytic reduction and anti-bacterial activity of biosynthesized silver nanoparticles against multi drug resistant Staphylococcus saprophyticus BDUMS 5 (MN310601)

In this study, silver nanoparticles (Ag NPs) was eco-friendly synthesized using purified flavonoid rich content of Morinda citrifolia (M. citrifolia) extract. The synthesized Ag NPs was exhibited at 420 nm in UV-spectrometer, and surface morphology with available chemical composition, shape and size of the Ag NPs were confirmed by X-ray diffraction (XRD) variation, scanning electron microscope (SEM) with energy dispersive X-ray spectroscopy (EDX) and transmission electron microscope (TEM). In addition, the excellent phytochemicals and anti-oxidant activity of the Ag NPs were confirmed by total anti-oxidant and DPPH free radical scavenging assays. Further, the concentration dependent inhibition of synthesized Ag NPs against biofilm forming Staphylococcus aureus (S. aureus) was confirmed by minimum inhibition concentration (MIC). The growth cells were arrested in the log phase of the culture and detected by flow cytometry analysis. In addition, the bacterial viability, exopoly-saccharide degradation, intracellular membrane damage, matured biofilm inhibition, architectural damage and morphological alteration were confirmed by confocal laser scanning electron microscope (CLSM) and SEM. Furthermore, the synthesized Ag NPs reacted with methylene blue (MB) dye molecules has 100% degradation at an irradiation time of 140 min. Conclusively, the eco-friendly synthesized Ag NPs has excellent anti-oxidant, anti-bacterial through intracellular membrane damage, cell cycle arrest and methylene blue dye removal.National Natural Science Foundation of China (NSFC) 41950410573 31670009 China Postdoctoral Science Foundation 2019M663213 King Saud University RG-1438-09

IL-1β reduces cardiac lymphatic muscle contraction via COX-2 and PGE2 induction: Potential role in myocarditis

The role of lymphatic vessels in myocarditis is largely unknown, while it has been shown to play a key role in other inflammatory diseases. We aimed to investigate the role of lymphatic vessels in myocarditis using in vivo model induced with Theiler’s murine encephalomyelitis virus (TMEV) and in vitro model with rat cardiac lymphatic muscle cells (RCLMC). In the TMEV model, we found that upregulation of a set of inflammatory mediator genes, including interleukin (IL)-1β, tumor necrosis factor (TNF)-αand COX-2 were associated with disease activity. Thus, using in vitro collagen gel contraction assays, we decided to clarify the role(s) of these mediators by testing contractility of RCLMC in response to IL-1β and TNF-α individually and in combination, in the presence or absence of: IL-1 receptor antagonist (Anakinra); cyclooxygenase (COX) inhibitors inhibitors (TFAP, diclofenac and DuP-697). IL-1β impaired RCLMC contractility dose-dependently, while co-incubation with both IL-1β and TNF-α exhibited synergistic effects in decreasing RCLMC contractility with increased COX-2 expression. Anakinra maintained RCLMC contractility; Anakinra blocked the mobilization of COX-2 induced by IL-1β with or without TNF-α. COX-2 inhibition blocked the IL-1β-mediated decrease in RCLMC contractility. Mechanistically, we found that IL-1β increased prostaglandin (PG) E2 release dose-dependently, while Anakinra blocked IL-1β mediated PGE2 release. Using prostaglandin E receptor 4 (EP4) receptor antagonist, we demonstrated that EP4 receptor blockade maintained RCLMC contractility following IL-1β exposure. Our results indicate that IL-1β reduces RCLMC contractility via COX-2/PGE2 signaling with synergistic cooperation by TNF-α. These pathways may help provoke inflammatory mediator accumulation within the heart, driving progression from acute myocarditis into dilated cardiomyopathy.This work funded by a graduate research fellowship from the Center for Cardiovascular Diseases and Sciences, LSU Health Science Center- Shreveport (M. Al-Kofahi, F. Sato and S. Omura), a grant from the Department of Defense (W81XWH-11-1-0577, J.S. Alexander), the German Research Foundation (DFG, BE 5619/1-1, F. Becker), the National Institute of General Medical Sciences of the National Institutes of Health (NIH Award P30GM110703, I. Tsunoda), the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan (F. Sato), the Faculty Assistance and Development Research Grants from the Kindai University Research Enhancement Grant (F. Sato and S. Omura), the KAKENHI from the Japan Society for the Promotion of Science (JP17K15628, F. Sato; and JP16H07356, I. Tsunoda), and NIH/NHLBI (ML125572-01A1, F.N.E. Gavins)

Mechanical and kinetic effects of shortened tropomyosin reconstituted into myofibrils

The effects of tropomyosin on muscle mechanics and kinetics were examined in skeletal myofibrils using a novel method to remove tropomyosin (Tm) and troponin (Tn) and then replace these proteins with altered versions. Extraction employed a low ionic strength rigor solution, followed by sequential reconstitution at physiological ionic strength with Tm then Tn. SDS-PAGE analysis was consistent with full reconstitution, and fluorescence imaging after reconstitution using Oregon-green-labeled Tm indicated the expected localization. Myofibrils remained mechanically viable: maximum isometric forces of myofibrils after sTm/sTn reconstitution (control) were comparable (~84%) to the forces generated by non-reconstituted preparations, and the reconstitution minimally affected the rate of isometric activation (kact), calcium sensitivity (pCa50), and cooperativity (nH). Reconstitutions using various combinations of cardiac and skeletal Tm and Tn indicated that isoforms of both Tm and Tn influence calcium sensitivity of force development in opposite directions, but the isoforms do not otherwise alter cross-bridge kinetics. Myofibrils reconstituted with Δ23Tm, a deletion mutant lacking the second and third of Tm’s seven quasi-repeats, exhibited greatly depressed maximal force, moderately slower kact rates and reduced nH. Δ23Tm similarly decreased the cooperativity of calcium binding to the troponin regulatory sites of isolated thin filaments in solution. The mechanisms behind these effects of Δ23Tm also were investigated using Pi and ADP jumps. Pi and ADP kinetics were indistinguishable in Δ23Tm myofibrils compared to controls. The results suggest that the deleted region of tropomyosin is important for cooperative thin filament activation by calcium

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

Embryonic Stem Cells: New Possible Therapy for Degenerative Diseases That Affect Elderly People

The capacity of embryonic stem (ES) cells for virtually unlimited self renewal and differentiation has opened up the prospect of widespread applications in biomedical research and regenerative medicine. The use of these cells would overcome the problems of donor tissue shortage and implant rejection, if the cells are made immunocompatible with the recipient. Since the derivation in 1998 of human ES cell lines from preimplantation embryos, considerable research is centered on their biology, on how differentiation can be encouraged toward particular cell lineages, and also on the means to enrich and purify derivative cell types. In addition, ES cells may be used as an in vitro system not only to study cell differentiation but also to evaluate the effects of new drugs and the identification of genes as potential therapeutic targets. This review will summarize what is known about animal and human ES cells with particular emphasis on their application in four animal models of human diseases. Present studies of mouse ES cell transplantation reveal encouraging results but also technical barriers that have to be overcome before clinical trials can be considered