Role of Fe–N–C Geometry Flip-Flop in Bistability in Fe(tetrazol-2-yl)4(C2H5CN)2-Type Core Based Coordination Network

2012 ◽  
Vol 51 (23) ◽  
pp. 12630-12637 ◽  
Author(s):  
Agata Białońska ◽  
Robert Bronisz
Keyword(s):  
Flip Flop ◽  
Coordination Network

Role of cholesterol flip-flop in oxidized lipid bilayers

2021 ◽  
Author(s):  
Phansiri Boonnoy ◽  
Viwan Jarerattanachat ◽  
Mikko Karttunen ◽  
Jirasak Wong-ekkabut
Keyword(s):  
Lipid Bilayers ◽  
Flip Flop

scholarly journals Structural insights into the molecular mechanisms of the Mycobacterium evolvability factor Mfd

2019 ◽  
Author(s):  
Sivasankar Putta ◽  
Swayam Prabha ◽  
Vinayak Bhat ◽  
Gavin C. Fox ◽  
Martin A. Walsh ◽  
...  
Keyword(s):  
Bound States ◽  
Molecular Mechanisms ◽  
Nucleotide Binding ◽  
Dna Translocation ◽  
Flip Flop ◽  
Functional Studies ◽  
Negative Stain ◽  
Structural Insights ◽  
Dna Translocase

ABSTRACTMfd is a highly conserved ATP dependent DNA translocase that mediates the role of Transcription-Coupled-DNA-Repair(TCR) in bacteria. The molecular mechanisms and conformational remodelling that occurs in Mfd upon ATP binding, hydrolysis, and DNA translocation are poorly defined. Here we report a series of crystal and electron microscopy(EM) structures of Mfd from Mycobacterium tuberculosis (MtbMfd) and Mycobacterium smegmatis Mfd, solved in both the apo and nucleotide-bound states. The structures reveal the mechanism of nucleotide-binding, which lead to the remodeling of the Walker A motif at the catalytic pocket, inducing a flip-flop action of the hinge and flexible linker regions. Specifically, nucleotide binding unlocks the Translocation in RecG motif of the D6-domain to induce a ratchet-like motion. Functional studies of MtbMfd-RNAP complexes show that MtbMfd rescues stalled Transcription Elongation Complexes. We also report negative-stain and cryo-EM single particle reconstructions of MtbMfd higher order oligomer, that reveal an unexpected dodecameric assembly state. Given that Mfd accelerates the evolution of antimicrobial resistance(AMR), our results establish a framework for the design of new “anti-evolution” therapeutics to counter AMR.

Thermal and Light-Induced Spin Switching Dynamics in the 2D Coordination Network of {[Zn1-xFex(bbtr)3](ClO4)2}∞: The Role of Cooperative Effects

2012 ◽  
Vol 51 (18) ◽  
pp. 9714-9722 ◽  
Author(s):  
Pradip Chakraborty ◽  
Cristian Enachescu ◽  
Christophe Walder ◽  
Robert Bronisz ◽  
Andreas Hauser
Keyword(s):  
Cooperative Effects ◽  
Coordination Network ◽  
Switching Dynamics ◽  
Spin Switching

TPCK Induces Apoptosis in Human Acute Myeloid Leukemia U-937 Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4478-4478
Author(s):  
Julia Mazar ◽  
Alexandra Lichtenstein ◽  
Leora Katz ◽  
Ofer Shpilberg ◽  
Itai Levi ◽  
...  
Keyword(s):  
Chromatin Condensation ◽  
Annexin V ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Concentration Dependent Manner ◽  
Flip Flop ◽  
Induced Apoptosis

Abstract Many types of antitumor therapy in general and AML in particular exert their effect by activating apoptosis. Apoptosis of AML cells can be induced by cytostatic drugs, corticosteroids, and radiation. Recently, the role of different proteases as possible targets for chemotherapy was described. N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a chymotrypsin-like protease (CLP) inhibitor was shown to exert a dual effect on leukemic cells: proapoptotic and antiapoptotic. In the present study the mechanism of its proapoptotic effect was addressed. It was found that the CLP inhibitors, TPCK and 3,4 dichloroisicoumarine induced apoptosis in a time- and concentration-dependent manner. Apoptosis was accompanied by a decrease in mitochondrial membrane potential, cytochrome c release, caspase-3 (but not caspase-8) activation, PS flip-flop (measured by Annexin-V staining followed by flow cytometry analysis) and chromatin condensation, but not fragmentation (detected by acridine orange/ethidium bromide staining). All apoptotic processes induced by TPCK were completely inhibited by cycloheximide. The ability of cycloheximide to inhibit TPCK-induced cell death suggests that protein synthesis plays a role in TPCK-induced apoptosis. Additionaly, the proapoptotic effect of TPCK was abolished by elimination of glucose from the medium. The data supports the role of mitochondria in this process. In the present study the apoptotic pathway driven by inhibition of CLP was demonstrated. Moreover, these findings suggest possible ways of preventing the proapoptotic activity of TPCK and thereby enhancimg its antiapoptotic action.

scholarly journals Magnetic resonance “flip-flop” in idiopathic intracranial hypertension

2011 ◽  
Vol 02 (01) ◽  
pp. 084-086 ◽  
Author(s):  
Uttam George ◽  
Geetika Bansal ◽  
Jeyaraj Pandian
Keyword(s):  
Magnetic Resonance ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Resonance Imaging ◽  
Flip Flop ◽  
Csf Pressure ◽  
Intracranial Lesions ◽  
Magnetic Resonance Imaging Mri

ABSTRACTIdiopathic intracranial hypertension (IIH) is a headache syndrome with raised CSF pressure in the absence of an intracranial mass lesion. Though earlier confined to excluding intracranial lesions, magnetic resonance imaging (MRI) in recent years has been shown to identify intracranial changes from prolonged raised CSF pressure, suggestive of IIH. We present the MRI and TOF (time-of-flight) venography findings involving the orbit, sella tursica and cerebral venous structures in a 45-year-old lady with IIH and illustrate their reversibility (“flip-fl op”) following CSF drainage. Our case highlights the role of imaging in evaluation and follow-up of patients with IIH, without the need for repeated lumbar punctures to monitor pressures.

scholarly journals Membrane remodeling by the lytic fragment of sticholysin II: implications for the toroidal pore model

2019 ◽  
Author(s):  
H. Mesa-Galloso ◽  
P.A. Valiente ◽  
R.F. Epand ◽  
M.E. Lanio ◽  
R.M. Epand ◽  
...  
Keyword(s):  
Pore Formation ◽  
Membrane Curvature ◽  
Membrane Remodeling ◽  
Structural Element ◽  
Flip Flop ◽  
Negatively Curved ◽  
N Terminus ◽  
Toroidal Pore ◽  
Insight Into

AbstractSticholysins are pore-forming toxins of biomedical interest and represent a prototype of proteins acting through the formation of protein-lipid or toroidal pores. Peptides spanning the N-terminus of sticholysins can mimic their permeabilizing activity and together with the full-length toxins have been used as a tool to understand the mechanism of pore formation in membranes. However, the lytic mechanism of these peptides and the lipid shape modulating their activity are not completely clear. In this paper, we combine molecular dynamics (MD) simulations and experimental biophysical tools to dissect different aspects of the pore-forming mechanism of StII1-30, a peptide derived from the N-terminus of sticholysin II. With this combined approach, membrane curvature induction and flip-flop movement of the lipids were identified as two important membrane remodeling steps mediated by StII1-30-pore forming activity. Pore-formation by this peptide was enhanced by the presence of the negatively-curved lipid phosphatidylethanolamine (PE) in membranes. This lipid emerged not only as a facilitator of membrane interactions but also as a structural element of the StII1-30-pore that is recruited to the pore ring upon its assembly. Collectively, these new findings support a toroidal model for the architecture of the pore formed by this peptide and provide new molecular insight into the role of PE as a membrane component that easily accommodates into the ring of toroidal pores aiding in its stabilization. This study contributes to a better understanding of the molecular mechanism underlying the permeabilizing activity of StII1-30 and peptides or proteins acting via a toroidal pore mechanism and offers an informative framework for the optimization of the biomedical application of this and similar molecules.State of significanceWe provide evidence about the ability of StII1-30 to form toroidal pores. Due to pore assembly, StII1-30-pore induces membrane curvature and facilitates flip-flop movement of the lipids. The negatively-curved lipid PE relocates from the membrane into the pore ring, being also a structural element of the pore StII1-30 forms. This peptide emerged as a new tool, together with the full-length toxin, to understand the mechanism of toroidal pore formation in membranes. This study provides new molecular insight into the role of curved lipids as co-factors of toroidal pores, which could aid in its stabilization by easily accommodating into the ring. This framework could underpin strategies for the rational use of peptides or proteins acting via toroidal pores.

Role of metformin in various pathologies: state-of-the-art microcapsules for improving its pharmacokinetics

2020 ◽  
Vol 11 (11) ◽  
pp. 733-753
Author(s):  
Ahmed Gedawy ◽  
Hani Al-Salami ◽  
Crispin R Dass
Keyword(s):  
Oral Bioavailability ◽  
Delivery Systems ◽  
First Line ◽  
Flip Flop ◽  
Therapeutic Goals ◽  
First Line Therapy ◽  
Particulate Delivery ◽  
Potential Tool

Metformin was originally derived from a botanical ancestry and became the most prescribed, first-line therapy for Type 2 diabetes in most countries. In the last century, metformin was discovered twice for its antiglycemic properties in addition to its antimalarial and anti-influenza effects. Metformin exhibits flip-flop pharmacokinetics with limited oral bioavailability. This review outlines metformin pharmacokinetics, pharmacodynamics and recent advances in polymeric particulate delivery systems as a potential tool to target metformin delivery to specific tissues/organs. This interesting biguanide is being rediscovered this century for multiple clinical indications as anticancer, anti-aging, anti-inflammatory, anti-Alzheimer’s and much more. Microparticulate delivery systems of metformin may improve its oral bioavailability and optimize the therapeutic goals expected.

Design of Integrated Circuit of Electronic Musical Instruments and Leakage Protection Device

2014 ◽  
Vol 543-547 ◽  
pp. 572-575
Author(s):  
Cheng Liu
Keyword(s):  
Integrated Circuit ◽  
Output Voltage ◽  
Input Voltage ◽  
Musical Instrument ◽  
Voltage Regulation ◽  
Instrumentation Amplifier ◽  
Protection Device ◽  
Flip Flop ◽  
Load Regulation

Ethnic harmony can make the every chord has stability within tone. It can make the chord has strong logic which has the role of continuity. Functional and tonality of harmony have important relevance. Harmony cannot play the role of harmony in the application without the tonality. The national electronic musical instrument of the system treats MIC29151 as core regulator. It controls ADC0809 sampling through AT89S52 and displays output power timely. Leakage protection device achieves the leakage protection by an instrumentation amplifier AD623, voltage comparator LM2901 and CD4013 dual D flip-flop relay switch. The system can output 5V voltage stability and precise. When rate current is 1A and input voltage is 7~25V, output voltage regulation is 0.132%. When input voltage is 5.5~7V, output voltage is 5±0.05V. When input voltage is 7V, load regulation is 0.032% which is an ideal solution for national electronic musical instrument.

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