Podcasts about efflux

References Infect Immun. 2013 Dec; 81(12): 4478–4489 Cell Cycle. 2022; 21(11): 1121–1139. The Journal of Nutritional Biochem.2023.Volume 112, 109217 Lightfoot, G. 1964. "Early Morning Rain" https://youtu.be/ZFJ5Bj_put0?si=m1Ue7rFfk_ggSLR3 Simon ,P. 1968. "Old Friends" SImon and Garfunkle Bookends LP. https://youtu.be/7A76lTte8qE?si=rfk3Q6wTA6Nsiok7 Mozart, WA. 1782 Serenade in C. Minor K.388. https://youtu.be/R6iSGBNdqSw?si=S2eGPmcySUhw4uvU --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.11.548482v1?rss=1 Authors: Jukkola, J., Kaakinen, M., Singh, A., Moradi, S., Ferdinando, H., Myllyla, T., Kiviniemi, V., Eklund, L. Abstract: Abstract Background Inside the incompressible cranium, the volume of cerebrospinal fluid (CSF) is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering (BPL) on fluorescent CSF tracer absorption into the systemic blood circulation. Methods BPL was performed by an i.v. administration of nitric oxide donor sodium nitroprusside (5 g kg-1 min-1) or the Ca2+-channel blocker nicardipine hydrochloride (0.5 g kg-1 min-1) for 10 and 15 to 40 mins, respectively. The effect of BPL on CSF clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. Results Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 {+/-} 19.6% and 22.0 {+/-} 2.5%, while temporarily elevating in intracranial pressure by 14.0 {+/-} 6.0% and 11.6 {+/-} 2.0%, respectively. BPL significantly increased tracer accumulation into deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by BPL into the systemic circulation was markedly reduced (-66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes. Conclusions This is the first study showing that CSF clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced CSF clearance by BPL may have therapeutic potential in diseases with dysregulated CSF flow. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Effect of Patient Positioning on Ureteral Efflux During Intraoperative Cystoscopy: a Randomized Controlled Trial w/ Dr. Sheena Galhotrahttps://www.jmig.org/article/S1553-4650(22)00363-6/fulltext 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.15.516693v1?rss=1 Authors: Mochizuki, T., Tanigawa, T., Shindo, S., Suematsu, M., Oguchi, Y., Mioka, T., Kato, Y., Fujiyama, M., Hatano, E., Yamaguchi, M., Chibana, H., Abe, F. Abstract: The fungal cell wall is the first barrier against diverse external stresses, such as high hydrostatic pressure. This study explores the roles of osmoregulation and the cell wall integrity (CWI) pathway in response to the high pressure in the yeast Saccharomyces cerevisiae. We demonstrate the roles of the transmembrane mechanosensor Wsc1 and aquaglyceroporin Fps1 in an underlying protective mechanism to avoid cellular rupture under high pressure. The promotion of water influx into cells at 25 MPa, as evident by an increase in cell volume and a loss of the plasma membrane eisosome structure, promotes the activation of Wsc1, an activator of the CWI pathway. The downstream mitogen-activated protein kinase Slt2 was hyperphosphorylated at 25 MPa. Glycerol efflux increases via Fps1 phosphorylation, which is initiated by downstream components of the CWI pathway, and contributes to the reduction in intracellular osmolarity under high pressure. Herein, the elucidation of a cellular pathway that is used as a protective mechanism against high pressure could potentially be translated to mammalian cells and could help to understand cellular mechanosensation and adaptation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.12.511914v1?rss=1 Authors: Di, A., Huang, L. S., Zhou, B., Toth, P. T., Krishnan, Y., Malik, A. B. Abstract: Potassium efflux via the two pore K+ channel TWIK2 is a requisite step for the activation of the NLRP3 inflammasome, however it is unclear how the efflux is activated in response to cues. Here we report that during homeostasis, TWIK2 resides in endosomal compartments. TWIK2 is transported by endosomal fusion to the plasmalemma in response to increased extracellular ATP resulting in extrusion of K+ ATP-induced endosomal TWIK2 plasmalemma translocation is regulated by Rab11a. Deleting Rab11a or ATP ligated purinergic receptor P2X7 prevented endosomal fusion with the plasmalemma and K+ efflux and NLRP3 inflammasome activation in macrophages. Adoptive transfer of Rab11a-deleted macrophages into mouse lungs prevented NLRP3 inflammasome activation and inflammatory lung injury. Rab11a-mediated endosomal trafficking in macrophages thus regulates TWIK2 abundance and activity on the cell surface and downstream activation of the NLRP3 inflammasome. Endosomal trafficking of TWIK2 to the plasmalemma is therefore a potential therapy target in acute or chronic inflammatory states. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A podcast about a chair. What could be more enticing to send you off to sleep? 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.07.372722v1?rss=1 Authors: Tyurikova, O., Shih, P.-Y., Dembitskaya, Y., Savtchenko, L. P., McHugh, T., Rusakov, D. A., Semyanov, A. Abstract: Glutamatergic transmission in the hippocampus prompts K+ efflux through postsynaptic N-methyl-D-aspartate receptors (NMDARs). This K+ efflux depolarizes local presynaptic terminals, boosting glutamate release, but whether it also depolarizes local astrocytic processes, thus affecting glutamate uptake, remains unknown. Here, we find that the pharmacological blockade, or conditional knockout, of NMDARs suppresses the progressive use-dependent increase in the amplitude and decay time of the astrocytic glutamate transporter current (IGluT), whereas blocking the astrocytic inward-rectifying K+ channels prevents the decay time increase only. Glutamate spot-uncaging reveals that local astrocyte depolarization, rather than extracellular K+ rises on their own, reduces the amplitude and prolong the decay of IGluT. Biophysical simulations of a realistic 3D astrocyte confirm that local transient elevations of extracellular K+ can inhibit local glutamate uptake in fine astrocytic processes. We conclude that K+ efflux through postsynaptic NMDARs can transiently depolarize local cell membranes, which facilitates presynaptic release while reducing local glutamate uptake. Optical glutamate sensor imaging and a two-pathway test relate postsynaptic K+ efflux to enhanced extrasynaptic glutamate signaling. Thus, the frequency of synaptic discharges can control the way the network handles its synaptic signal exchange. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.21.349639v1?rss=1 Authors: Kumar, S., Athreya, A., Gulati, A., Nair, R. M., Penmatsa, A. Abstract: Multi-drug efflux is a major mechanism of acquiring antimicrobial resistance among superbugs. In this study, we report the X-ray structure of NorC, a 14 transmembrane major facilitator superfamily member that is implicated in fluoroquinolone resistance in drug-resistant Staphylococcus aureus strains, at a resolution of 3.6 angstroms. The NorC structure was determined in complex with a single-domain camelid antibody that interacts at the extracellular face of the transporter and stabilizes it in an outward-open conformation. The complementarity determining regions of the antibody enter and block solvent access to the interior of the vestibule, thereby inhibiting alternating-access. NorC specifically interacts with an organic cation, tetraphenylphosphonium, although it does not demonstrate an ability to transport it. The interaction is compromised in the presence of NorC-antibody complex, consequently establishing a strategy to detect and block NorC and related efflux pumps through the use of single-domain camelid antibodies. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.14.296756v1?rss=1 Authors: Budiardjo, S. J., Ikujuni, A. P., Firlar, E., Cordova, A., Kaelber, J., Slusky, J. S. G. Abstract: Overexpression of tripartite efflux pump systems in gram-negative bacteria are a principal component of antibiotic resistance. High-yield purification of the outer membrane component of these systems will enable biochemical and structural interrogation of their mechanisms of action and allow testing of compounds that target them. However, preparation of these proteins is typically hampered by low yields requiring laborious large-scale efforts. If refolding conditions can be found, refolding these proteins from inclusion bodies can lead to increased yields as compared to membrane isolations. Here, we develop a concentration-dependent folding protocol for refolding TolC, the outer membrane component of the antibiotic efflux pump from Escherichia coli. We show that by our method of re-folding, homotrimeric TolC remains folded in SDS-PAGE, retains binding to an endogenous ligand, and recapitulates the known crystal structure by single particle cryoEM analysis. We find that a key factor in successful re-folding is a concentration dependence of TolC oligomerization. We extended the scheme to CmeC, a homologous protein from Campylobacter jejuni, and find that concentration-dependent oligomerization is a general feature of these systems. Because outer-membrane efflux pump components are ubiquitous across gram-negative species, we anticipate that incorporating a concentration step in re-folding protocols will promote correct refolding allowing for reliable, high-yield preparation of this family of proteins. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.18.255323v1?rss=1 Authors: Lombardi, A., Jedlicka, P., Luhmann, H. J., Kilb, W. Abstract: The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed immature CA3 neuron. These computational experiments demonstrated that glutamatergic co-stimulation enhances GABA receptor-mediated Cl- influx at low and attenuates or reverses the Cl- efflux at high initial [Cl-]i. The size of glutamatergic influence on GABAergic Cl--fluxes depends on the conductance, decay kinetics, and localization of glutamatergic inputs. Surprisingly, the glutamatergic shift in GABAergic Cl--fluxes is invariant to latencies between GABAergic and glutamatergic inputs over a substantial interval. In agreement with experimental data, simulations in a reconstructed CA3 pyramidal neuron with physiological patterns of correlated activity revealed that coincident glutamatergic synaptic inputs contribute significantly to the activity-dependent [Cl-]i changes. Whereas the influence of spatial correlation between distributed glutamatergic and GABAergic inputs was negligible, their temporal correlation played a significant role. In summary, our results demonstrate that glutamatergic co-stimulation had a substantial impact on ionic plasticity of GABAergic responses, enhancing the destabilization of GABAergic inhibition in the mature nervous systems, but suppressing GABAergic [Cl-]i changes in the immature brain. Therefore, glutamatergic shift in GABAergic Cl--fluxes should be considered as a relevant factor of short term plasticity. Copy rights belong to original authors. Visit the link for more info

I read an interesting article about how obesity causes people to have more difficulty fighting influenza, and to make antibodies when given the flu vaccine, so I talk about other steps that you can take. It’s not just about how much HDL you have, but how efficiently your HDL removes cholesterol from your arteries, known […]

At ASM Microbe in San Francisco, Nels and Vincent meet up with Paul Turner to talk about evolutionary considerations in using bacteriophages to treat infections with antibiotic-resistant bacteria. Hosts: Nels Elde and Vincent Racaniello Guest: Paul Taylor Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiEVO Turner Lab at Yale Phage therapy: A renewed approach (Cell Host Microbe) Phage treatment of aortic graft (Evol Med Pub Health) Time stamps by Jolene. Thanks! Science Picks Nels- Science Glass Vincent- Phage therapy for disseminated Mycobacterial infection Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv

High-density lipoproteins, or HDLs, are macromolecular assemblies that play a key role in lipid transport, but also exert effects in endothelial function, thrombosis, and inflammation.  A recent focus by several groups on HDL function rather than HDL cholesterol revealed that efflux capacity was inversely associated with coronary artery disease.  Traditionally, cholesterol efflux is measured using a cell-based assay where cultured microphages are treated with radioactively-labeled cholesterol and subsequently exposed to a cholesterol acceptor. A recent study that appeared in the February 2019 issue of Clinical Chemistry took a completely different approach and assessed the lipoprotein proteome by using liquid chromatography and tandem mass spectrometry to measure 21 lipoprotein associated proteins.

Commentary by Dr. Valentin Fuster

Adam Bixler of Efflux Systems joins us. In startup news, the 3 most abstract tips to make your startup succeed, the 5 best presentation apps for your startup needs, non-expensive ways to make your small business feel big, and much more. Stay tuned!

Commentary by Dr. Valentin Fuster

Adam Bixler is the Cofounder and Chief Ops Officer for Efflux Systems. Offering a security operations solution that detects lateral movement and attacker tradecraft. Full Show Notes: http://wiki.securityweekly.com/wiki/index.php/SSW_Episode15 Take the Security Weekly Survey: www.securityweekly.com/survey Visit http://securityweekly.com/category/ssw/ for all the latest episodes!

Adam Bixler is the Cofounder and Chief Ops Officer for Efflux Systems. Offering a security operations solution that detects lateral movement and attacker tradecraft. Full Show Notes: http://wiki.securityweekly.com/wiki/index.php/SSW_Episode15 Take the Security Weekly Survey: www.securityweekly.com/survey Visit http://securityweekly.com/category/ssw/ for all the latest episodes!

Adam Bixler of Efflux Systems joins us. In startup news, the 3 most abstract tips to make your startup succeed, the 5 best presentation apps for your startup needs, non-expensive ways to make your small business feel big, and much more. Stay tuned!

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Cell-based drug absorption assays are an essential component of ADME/Tox testing for lead compounds. In this report, Apparent Permeability (Papp) and Efflux data demonstrate how an automated procedure, when compared to manual processing, provides a method that is less variable and is capable of delivering a more accurate assessment of a compound’s absorption characteristics.

In this report, Apparent Permeability (Papp) and Efflux data demonstrate how an automated procedure, when compared to manual processing, provides a method that is less variable and is capable of delivering a more accurate assessment of a compound’s absorption characteristics.

Tue, 1 Jan 2008 12:00:00 +0100 https://epub.ub.uni-muenchen.de/16840/1/10_1159_000179360.pdf Ochsenkühn, Thomas