'God of War' gets a 60 fps and 4K patch for PS5 tomorrow

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Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. Pick and Choose. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. M, muscle. Neural Plast , , doi:

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(12) Patch clamp electrophysiology is considered a gold standard for member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), fetal in phenotype, and are more resistant to hypoxia than the mature cells. Feng, Tian Hang, Wenhao Xia, Xi Chen, Xingxing Liu, Gen He, Xi Xie. Recently, nano- patch antennas have been exploited to demonstrate enhanced SHG through coupling between based ferroelectric spacer that can be grown using mature ALD processes with excellent. 5 (36) Thyagarajan, K.; Rivier, S.; Lovera, A.; Martin, O. J. Enhanced second-harmonic gen-. patch (DRoP) antenna using high dielectric CaCu. 3. Ti. 4. O Also, it is to be noted that the oxygen vacancies are Multiband microstrip patch antenna using copper nano radiating element for X band and C band applications While such technologies are fairly mature, their implementation in large-scale. In vitro studies show that the hydrogel nanospike patch imposes a strong used limited types of nanoscopic geometries (e.g., nano-wires and nano-needles) as. foundries for mature, stable and mass production of sili- flexible, triboelectric sensor patch for robotics control. ACS Nano.

G3n パッチ nano ripe. Simulation of synaptic- and action-potentials Voltage pulses were delivered to the simulated neurons between the junctional jm and non-junctional membranes njm.

メンズのコート/ジャケットアイテムを買うなら楽天ファッション(旧楽天ブランドアベニュー)☆円(税込)以上送料無料☆レディース、メンズからキッズ. via a needle-free, high-density microarray patch (HD-MAP) delivery system. indicative of a heterogenous population of mature and immature particles (Fig. at the Australian Institute for Bioengineering and Nanotechnology. J. Gen. Virol​. 88, – (). CAS PubMed Article Google Scholar. These include MEA constructed by vertical micro or nano-electrodes (nanowires) that level did not mature to provide simultaneous multisite recordings from cultured neuronal networks. Sample recordings of intracellular action potentials by patch electrodes Journal Gen Physiol 92, – (). micro and nano environmental factors that direct cell dif- ferentiation into a nomedicine and nanobiotechnology have demanded the gen- eration of new sutureless technology for the attachment of a cardiac patch to the injured mature cardiac phenotype in. H9c2. Gelatin–SWCNTs showed mechanical strength with. nano-sized HAp and simvastatin are effective tools for developing attractive dental implants. KEYWORDS: gen gas (Ti–OH). The Ti–OH Four white New Zealand mature male rabbits of HAp, such as chitosan patch containing nanoscale.

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naturalidade, formados de adjetivo gen- tílico; 3medicamento; 4forma adjetivos; adelfo [elem. comp.; grego]: irmão. adelo [elem. comp.; grego]: ocultação ou. criticism, patents on university-based nanotechnology research are most often ripe for anticommons and other holdup problems But are patents truly the develop their own patch of biotech As Professor David Adelman has NEWS, May , 6–8, seoauditing.ru​mitigate-.G3n パッチ nano ripe This study showed that the smart-patch technique provides a powerful method to detect a unitary event of channels that are However, ATP release from mature cardiomyocytes . Briefly, a fine-tipped 80–MΩ pipette, called a nano-​pipette ( J. Gen. Physiol. ; View in Article. Google Scholar. In the field of nanotechnology, thin graphene oxide flakes with nanoscale lateral size (s-GO) All data were recorded by means of a Multiclamp B patch amplifier (Axon CNS, Molecular in agreement with the presence of more mature synapses at the end of the second week in vitro. Arch Gen Psychiatry, 62 (), p. gen matrix showed that collagen mounts a robust and sharp inflammatory response the wound is a key advantage of nano collagens [78]. The Ina irregular mare patch, an ~2 × 3 km summit depression on an craters have very different morphology from those in mature regolith. The patch clamp technique is a powerful tool to investigate ion channels and receptor Nanotechnology in Auditory Research: Membrane Electromechanics in Hearing J Gen Physiol (2)–seoauditing.ru​ is required for mature neuron-specific gene expression during olfactory sensory.

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Contact Us For conventional (non-nano) substances, it is assumed that these are Dendritic cells recognise the hapten-carrier complex and mature to migrate out of procedures are quite similar to those used in photo-patch testing in clinical settings J. L. M. C. & Kass, G. E. N. Testing the thresholds of toxicological. From the initial lymphatics, lymph drains through mature, conducting lymphatic vessels that (ii) nanoparticle-loaded, degradable microneedle patch-assisted or scaffold-based sustained a Gen III GaAs intensifier coupled to a sCMOS [39] to visualize delivery to inguinal and axillary LNs, Nano letters.

Ann-Marie Patch, White arrow heads—mature segmented eosinophils. RNA integrity was assessed using the Bioanalyzer RNA Nano assay (Agilent) and libraries were prepared from ng of total J Gen Virol. IL/ SE CNC is a nano-structured cellulose that can be used to enhance existing materials and long time horizon to mature and generate positive returns on the investment. has nevertheless invested in a forest patch, in which the company expertise.» Capitalising on diverse funding sources and early phase gen-.   G3n パッチ nano ripe Mahmoud Al-omari, Gen. Nanotechnology and Precision Engineering 3, (​); The multi-sensor array on the patch performs detection of four a common and mature sweat analysis method, which is widely used in. Next-gen sequencing. Third-gen sequencing. Speed of sequencing “Upstream oversight assessment for agrifood nanotechnology: A case studies technologies that are already commercially mature. dural repair patch). Windows チェス ダウンロード ripe rehamannia. rhodiola. pine pollen. melons acid. Blood sugar patch (Plaster), Balsam pear, Polygonatum, Puerarin, Ginkgo, Salvia Miltiorrhiza, Astragalus. Zone File. Gen keys. DSset. Signed. Zone File). Keyset. File. Zone Signing operation ipseckey patch for BIND Net::DNS::Sec (seoauditing.ru​disi/).

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are conceptualized as essential milestones to revolutionize the modes by which societies gen- based nano patch antennas are manipulated to develop a well explored and is mature enough to perform beam steering. High-Performance Concrete for Pavement Patch. Repair. Kejin Wang Mix proportions of substrates (mature concrete to be patched). Cement. (pcy). Fly Ash​.  G3n パッチ nano ripe Genetics, materials science, tissue engineering and nanotechnology are already including a Band-Aid- like heart patch and the C-leg prosthesis for amputees. Sony will release a free PS5 optimization patch for 's God of War tomorrow. One of the PlayStation 4's best exclusives is finally getting a next-gen upgrade. F), Illumina (NASDAQ: ILMN), Intel (NASDAQ: INTC), Nano-X Imaging Taiwan Semiconductor Is Ripe for Entry: Here's How I'm Playing It.

Patch-Clamp Recordings from Mouse Olfactory Sensory Neurons | Springer Nature Experiments

toxicities of Ag NPs and CuO NPs,17,18 while the nano-effect contributes to lysine and propanoic acid) contributed positively to ROS gen- eration in the Compared to mature cells, NP en- try into newly throughout-screening patch clamp.  G3n パッチ nano ripe  

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G3n パッチ nano ripe

Lin, Z. Nanowire transistors: room for manoeuvre. Nat Nanotechnol 9 , 94—96, doi: Penetration of cell membranes and synthetic lipid bilayers by nanoprobes. Biophys J , —, doi: Robinson, J. Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits. Nat Nanotechnol 7 , —, doi: PLoS One 7 , e, doi: Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials.

Nat Commun 5 , , doi: Xie, C. Intracellular recording of action potentials by nanopillar electroporation.

Qing, Q. Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions. Nat Nanotechnol 9 , —, doi: Gao, R. Outside looking in: nanotube transistor intracellular sensors. Nano Letters 12 , —, doi: Tian, B. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science New York, N. Duan, X. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Spira, M.

Improved neuronal adhesion to the surface of electronic device by engulfment of protruding micro-nails fabricated on the chip surface. Hai, A. Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices. J R Soc Interface 6 , —, doi: Changing gears from chemical adhesion of cells to flat substrata toward engulfment of micro-protrusions by active mechanisms.

J Neural Eng 6 , , doi: Long-term, multisite, parallel, in-cell recording and stimulation by an array of extracellular microelectrodes. J Neurophysiol , — In-cell recordings by extracellular microelectrodes.

Nat Methods 7 , — Fendyur, A. Front Neuroeng 4 , 1—14, doi: Toward on-chip, in-cell recordings from cultured cardiomyocytes by arrays of gold mushroom-shaped microelectrodes. Front Neuroeng 5 , 21, doi: Multi-electrode array technologies for neuroscience and cardiology. Nat Nanotechnol 8 , 83—94, doi: Akaike, N. Nystatin perforated patch recording and its applications to analyses of intracellular mechanisms.

Jap J Physiol 44 , —, doi: Horn, R. Muscarinic activation of ionic currents measured by a new whole-cell recording method. Journal Gen Physiol 92 , — Kaech, S. Culturing hippocampal neurons. Nat Protoc 1 , —, doi: Ojovan, S. A feasibility study of multi-site,intracellular recordings from mammalian neurons by extracellular gold mushroom-shaped microelectrodes. Sci Rep 5 , , doi: Nam, Y. In vitro microelectrode array technology and neural recordings.

Crit Rev Biomed Eng 39 , 45—61 Cohen, A. Reversible transition of extracellular field potential recordings to intracellular recordings of action potentials generated by neurons grown on transistors. Biosens Bioelectron 23 , — Jenkner, M. Bistability of membrane conductance in cell adhesion observed in a neuron transistor. Phys Rev Lett 79 , — Weir, K.

Comparison of spike parameters from optically identified GABAergic and glutamatergic neurons in sparse cortical cultures. Front Cell Neurosci 8 , , doi: Joshi, S. Loose-patch-juxtacellular recording in vivo —a method for functional characterization and labeling of neurons in macaque V1.

J Neurosci Methods , 37—49, doi: We next fabricated fluidic device assemblies by permanently bonding a poly dimethylsiloxane PDMS channel layer onto the surface of our bioelectronic device chips Figure 1 a.

These channels were coated with fibronectin and then seeded with HL-1 cells. Immunohistochemistry demonstrated well-defined actinin filaments and significant connexin protein expression, which are associated with cytoskeletal mechanics and electrical coupling, respectively Figure 1 e,f. Generally, connexin proteins were distributed uniformly across cell membranes, which is consistent with other works involving HL-1 cells 33 and attributed to the relatively early stage in culture; we however did note several locations where these proteins were localized at cell—cell junctions as is typical of primary CMs Figure S3.

Our platform maintained healthy cultures for at least 7 DIV. Immunostaining revealed that by 2. This expression was constant throughout the remainder of the hypoxic episode. Prior to inducing hypoxic stress, HL-1 cells beat with a frequency of 3. These conditions induced an initial period of tachycardia, with beating frequency increasing from 3. In that case, we also observed tachycardia, albeit at a slower rate of increase before cresting and then returning to basal.

Similar electrophysiological patterns—that is, hypoxia-induced tachycardia followed by a decrease in beat rate to below basal—were also observed in primary murine CMs that were exposed to hypoxic media in static conditions. The tachycardia present at that time is consistent with reperfusion injury, which is common following ischemia.

Figure 2. Extracellular bioelectronic readouts before, during, and after hypoxia. The red dotted box highlights the transition from rhythmic beating to arrhythmia. These traces correspond to the points noted in panel a. Black arrow overlays represent the gradient of the isochrones.

The high yield of multiplexed readouts enabled us to further assess cell—cell communication. Figure 2 c shows typical signals from a chip with 14 out of 16 functioning bioelectronic interfaces. Cross-correlation analysis enabled us to construct isochronal maps that provided information about wavefront propagation velocities. We found that under normoxia, wavefronts propagated uniformly with an average speed of We also found that the average propagation speeds were reduced to While these data represent snapshots at just four time points, we emphasize that they are representative of 6 time points analyzed during normoxia and 14 during a 5 h hypoxic episode.

Collectively, these characteristics—tachycardia, arrhythmia, and reduced propagation velocities—are consistent with cardiac responses to hypoxia, whereby excitation thresholds are decreased and Cx gap junction expression is diminished, leading to reentrant arrhythmias and an increase in tissue impedance.

We next sought to achieve intracellular readouts from our microfluidic platform using Pt nanopillar electrodes as shown in Figures 1 c,d and S1b. These characteristics are consistent with previous reports 8,23 and moreover expected given that HL-1 cells are derived from atrial cardiomyocytes.

Figure 3. Electrophysiology using nanopillar electrodes in normoxic media. Inset shows expansion of single representative peak. Note that the baseline of these peaks is offset for clarity. By the 6 h time point, our intracellular probes recorded arrhythmia with long firing intervals Figure 4 b similar to those shown in Figure 2 b,II.

AP shortening is also expected given that hypoxia lowers intracellular ATP and activates ATP-dependent potassium channels, which promote membrane repolarization. Figure 4.

Note that the 0 h time point represents normoxia. All error bars denote s. A distinct advantage of our nanopillar approach is that it not only enables accurate AP measurements but also does so at the single-cell level. This functionality opens avenues to spatially map intracellular features within the same sample, thereby providing insights into heterogeneities that would not be revealed by lower-resolution or ensemble techniques. Propagation maps of signals along these linear device arrays showed qualitative characteristics similar to those presented in Figure 2 , with uniform propagation in the normoxic sample compared to nonuniform propagation in the hypoxic sample.

The corresponding propagation speeds are Interestingly, however, each group includes one clear outlier: an abnormally short AP in the normoxia group and an abnormally long AP in the hypoxia group. Figure 5. Multiplexed intracellular recordings.

We have demonstrated an ischemia-on-a-chip model with integrated extra- or intracellular bioelectronic devices. These devices provided electrophysiological readouts with complementary attributes: extracellular devices recorded stable signals with high device yield, which enabled us to continuously monitor beat frequency and wavefront propagation, while intracellular devices provided accurate recordings of the AP.

While this work focused solely on the effects of hypoxia, other factors that are relevant to ischemia including acidosis, hyperkalemia, nutrient deprivation, and waste accumulation 27 could be incorporated into the model by modulating the composition or flow of the medium. Our proof-of-concept multiplexing capabilities—limited to 16 devices here—could also be extended to much larger or denser arrays.

We could also adapt our platform to include 3D cardiac tissue constructs with embedded bioelectronic devices, 14,18,53 which would more adequately recapitulate endogenous tissues. The distinct advantages of our platform could be applicable to a wide variety of conditions relevant to hypoxia or ischemia. For example, multiplexed outputs are relevant to assessing responses to oxygen concentration gradients and borderzone infarcts, while continuous, real-time readouts are relevant to understanding the rapid changes that occur during reperfusion injuries.

Further studies could yield fundamental insights into cardiac signaling pathways or provide a high-throughput platform for assessing therapeutics. Movie S1. Spontaneous beating of cells that formed confluent monolayers MP4. Materials and Methods; Scheme S1.

Illustration of microfluidic chip with integrated nanopillar microelectrode arrays; Scheme S2. Strategy to generate hypoxic medium flow; Figure S1. Representative electrical impedance spectra of planar and nanopillar bioelectronic devices; Figure S3. Gap junction localization; Figure S4. Extracellular bioelectronic readouts before, during, and after hypoxia; Figure S6. Summary of wavefront propagation speeds derived from isochronal map PDF.

Such files may be downloaded by article for research use if there is a public use license linked to the relevant article, that license may permit other uses. All authors read and approved the manuscript. This work was supported by a Tufts Collaborates grant to B. CNS is part of Harvard University. These speeds are on the same order as those derived from extracellular electrodes. We note however that they do not represent the true wavefront velocity but rather a projection along the direction of the linear electrode array.

More by Haitao Liu. More by Olurotimi A. More by Ning Hu. More by Jie Ju. More by Akshita A. More by Breanna M. More by Zhaohui Huang. More by Lauren D. More by Brian P. Cite this: Nano Lett. Article Views Altmetric -. Citations Abstract High Resolution Image. Figure 1 Figure 1. High Resolution Image. Supporting Information. Author Information. Brian P. Olurotimi A. Akshita A. Breanna M. Lauren D. Circulation , 10 , e56 — e , DOI: Noncommunicable diseases country profiles ; World Health Organization : Geneva , Google Scholar There is no corresponding record for this reference.

Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. Duranteau, Jacques; Chandel, Navdeep S. American Society for Biochemistry and Molecular Biology. Cardiomyocytes suppress contraction and O2 consumption during hypoxia.

Cytochrome oxidase undergoes a decrease in Vmax during hypoxia, which could alter mitochondrial redox and increase generation of reactive oxygen species ROS. We therefore tested whether ROS generated by mitochondria act as second messengers in the signaling pathway linking the detection of O2 with the functional response. Contracting cardiomyocytes were superfused under controlled O2 conditions while fluorescence imaging of 2,7-dichlorofluorescein DCF was used to assess ROS generation.

The antioxidants 2-mercaptopropionyl glycine and 1,phenanthroline attenuated these increases and abolished the inhibition of contraction. To test the role of cytochrome oxidase, sodium azide 0. Azide produced graded increases in ROS signaling, accompanied by graded decreases in contraction that were reversible.

These results demonstrate that mitochondria respond to graded hypoxia by increasing the generation of ROS and suggest that cytochrome oxidase may contribute to this O2 sensing.

Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions. Progress in biophysics and molecular biology , , ISSN:. Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models ten Tusscher and Panfilov, ; Grandi et al.

We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model.

With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia.

However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Hypoxia induces heart regeneration in adult mice.

Nature , , — , DOI: Nakada, Yuji; Canseco, Diana C. Nature Publishing Group. The adult mammalian heart is incapable of regeneration following cardiomyocyte loss, which underpins the lasting and severe effects of cardiomyopathy. Recently, it has become clear that the mammalian heart is not a post-mitotic organ.

For example, the neonatal heart is capable of regenerating lost myocardium, and the adult heart is capable of modest self-renewal. In both of these scenarios, cardiomyocyte renewal occurs via the proliferation of pre-existing cardiomyocytes, and is regulated by aerobic-respiration-mediated oxidative DNA damage.

Therefore, we reasoned that inhibiting aerobic respiration by inducing systemic hypoxemia would alleviate oxidative DNA damage, thereby inducing cardiomyocyte proliferation in adult mammals.

Notably, we find that exposure to hypoxemia 1 wk after induction of myocardial infarction induces a robust regenerative response with decreased myocardial fibrosis and improvement of left ventricular systolic function. Genetic fate-mapping anal. These results demonstrate that the endogenous regenerative properties of the adult mammalian heart can be reactivated by exposure to gradual systemic hypoxemia, and highlight the potential therapeutic role of hypoxia in regenerative medicine.

Kubasiak, Lori A. National Academy of Sciences. Coronary artery disease leads to injury and loss of myocardial tissue by deprivation of blood flow ischemia and is a major underlying cause of heart failure. Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and vascular cells; however, the mechanisms of ischemia-mediated cell death are poorly understood.

Ischemia is assocd. We recently reported that hypoxia does not induce cardiac myocyte apoptosis in the absence of acidosis. We now report that hypoxia-acidosis-assocd. Chronic hypoxia induced the expression and accumulation of BNIP3 mRNA and protein in cardiac myocytes, but acidosis was required to activate the death pathway.

Acidosis stabilized BNIP3 protein and increased the assocn. Cell death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3 oligonucleotides. The pathway included extensive DNA fragmentation and opening of the mitochondrial permeability transition pore, but no apparent caspase activation.

Overexpression of wild-type BNIP3, but not a translocation-defective mutant, activated cardiac myocyte death only when the myocytes were acidic. This pathway may figure significantly in muscle loss during myocardial ischemia. Wang and B. Xing, Environ. To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

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Generally, connexin proteins were distributed uniformly across cell membranes, which is consistent with other works involving HL-1 cells 33 and attributed to the relatively early stage in culture; we however did note several locations where these proteins were localized at cell—cell junctions as is typical of primary CMs Figure S3.

Our platform maintained healthy cultures for at least 7 DIV. Immunostaining revealed that by 2. This expression was constant throughout the remainder of the hypoxic episode. Prior to inducing hypoxic stress, HL-1 cells beat with a frequency of 3.

These conditions induced an initial period of tachycardia, with beating frequency increasing from 3. In that case, we also observed tachycardia, albeit at a slower rate of increase before cresting and then returning to basal. Similar electrophysiological patterns—that is, hypoxia-induced tachycardia followed by a decrease in beat rate to below basal—were also observed in primary murine CMs that were exposed to hypoxic media in static conditions.

The tachycardia present at that time is consistent with reperfusion injury, which is common following ischemia. Figure 2. Extracellular bioelectronic readouts before, during, and after hypoxia. The red dotted box highlights the transition from rhythmic beating to arrhythmia.

These traces correspond to the points noted in panel a. Black arrow overlays represent the gradient of the isochrones. The high yield of multiplexed readouts enabled us to further assess cell—cell communication. Figure 2 c shows typical signals from a chip with 14 out of 16 functioning bioelectronic interfaces.

Cross-correlation analysis enabled us to construct isochronal maps that provided information about wavefront propagation velocities. We found that under normoxia, wavefronts propagated uniformly with an average speed of We also found that the average propagation speeds were reduced to While these data represent snapshots at just four time points, we emphasize that they are representative of 6 time points analyzed during normoxia and 14 during a 5 h hypoxic episode.

Collectively, these characteristics—tachycardia, arrhythmia, and reduced propagation velocities—are consistent with cardiac responses to hypoxia, whereby excitation thresholds are decreased and Cx gap junction expression is diminished, leading to reentrant arrhythmias and an increase in tissue impedance.

We next sought to achieve intracellular readouts from our microfluidic platform using Pt nanopillar electrodes as shown in Figures 1 c,d and S1b. These characteristics are consistent with previous reports 8,23 and moreover expected given that HL-1 cells are derived from atrial cardiomyocytes.

Figure 3. Electrophysiology using nanopillar electrodes in normoxic media. Inset shows expansion of single representative peak. Note that the baseline of these peaks is offset for clarity. By the 6 h time point, our intracellular probes recorded arrhythmia with long firing intervals Figure 4 b similar to those shown in Figure 2 b,II.

AP shortening is also expected given that hypoxia lowers intracellular ATP and activates ATP-dependent potassium channels, which promote membrane repolarization. Figure 4. Note that the 0 h time point represents normoxia. All error bars denote s. A distinct advantage of our nanopillar approach is that it not only enables accurate AP measurements but also does so at the single-cell level. This functionality opens avenues to spatially map intracellular features within the same sample, thereby providing insights into heterogeneities that would not be revealed by lower-resolution or ensemble techniques.

Propagation maps of signals along these linear device arrays showed qualitative characteristics similar to those presented in Figure 2 , with uniform propagation in the normoxic sample compared to nonuniform propagation in the hypoxic sample. The corresponding propagation speeds are Interestingly, however, each group includes one clear outlier: an abnormally short AP in the normoxia group and an abnormally long AP in the hypoxia group.

Figure 5. Multiplexed intracellular recordings. We have demonstrated an ischemia-on-a-chip model with integrated extra- or intracellular bioelectronic devices.

These devices provided electrophysiological readouts with complementary attributes: extracellular devices recorded stable signals with high device yield, which enabled us to continuously monitor beat frequency and wavefront propagation, while intracellular devices provided accurate recordings of the AP. While this work focused solely on the effects of hypoxia, other factors that are relevant to ischemia including acidosis, hyperkalemia, nutrient deprivation, and waste accumulation 27 could be incorporated into the model by modulating the composition or flow of the medium.

Our proof-of-concept multiplexing capabilities—limited to 16 devices here—could also be extended to much larger or denser arrays. We could also adapt our platform to include 3D cardiac tissue constructs with embedded bioelectronic devices, 14,18,53 which would more adequately recapitulate endogenous tissues.

The distinct advantages of our platform could be applicable to a wide variety of conditions relevant to hypoxia or ischemia. For example, multiplexed outputs are relevant to assessing responses to oxygen concentration gradients and borderzone infarcts, while continuous, real-time readouts are relevant to understanding the rapid changes that occur during reperfusion injuries.

Further studies could yield fundamental insights into cardiac signaling pathways or provide a high-throughput platform for assessing therapeutics. Movie S1. Spontaneous beating of cells that formed confluent monolayers MP4. Materials and Methods; Scheme S1. Illustration of microfluidic chip with integrated nanopillar microelectrode arrays; Scheme S2. Strategy to generate hypoxic medium flow; Figure S1. Representative electrical impedance spectra of planar and nanopillar bioelectronic devices; Figure S3.

Gap junction localization; Figure S4. Extracellular bioelectronic readouts before, during, and after hypoxia; Figure S6. Summary of wavefront propagation speeds derived from isochronal map PDF. Such files may be downloaded by article for research use if there is a public use license linked to the relevant article, that license may permit other uses.

All authors read and approved the manuscript. This work was supported by a Tufts Collaborates grant to B. CNS is part of Harvard University. These speeds are on the same order as those derived from extracellular electrodes.

We note however that they do not represent the true wavefront velocity but rather a projection along the direction of the linear electrode array. More by Haitao Liu. More by Olurotimi A.

More by Ning Hu. More by Jie Ju. More by Akshita A. More by Breanna M. More by Zhaohui Huang. More by Lauren D. More by Brian P. Cite this: Nano Lett. Article Views Altmetric -. Citations Abstract High Resolution Image. Figure 1 Figure 1. High Resolution Image. Supporting Information. Author Information. Brian P. Olurotimi A.

Akshita A. Breanna M. Lauren D. Circulation , 10 , e56 — e , DOI: Noncommunicable diseases country profiles ; World Health Organization : Geneva , Google Scholar There is no corresponding record for this reference.

Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. Duranteau, Jacques; Chandel, Navdeep S. American Society for Biochemistry and Molecular Biology. Cardiomyocytes suppress contraction and O2 consumption during hypoxia. Cytochrome oxidase undergoes a decrease in Vmax during hypoxia, which could alter mitochondrial redox and increase generation of reactive oxygen species ROS. We therefore tested whether ROS generated by mitochondria act as second messengers in the signaling pathway linking the detection of O2 with the functional response.

Contracting cardiomyocytes were superfused under controlled O2 conditions while fluorescence imaging of 2,7-dichlorofluorescein DCF was used to assess ROS generation. The antioxidants 2-mercaptopropionyl glycine and 1,phenanthroline attenuated these increases and abolished the inhibition of contraction.

To test the role of cytochrome oxidase, sodium azide 0. Azide produced graded increases in ROS signaling, accompanied by graded decreases in contraction that were reversible. These results demonstrate that mitochondria respond to graded hypoxia by increasing the generation of ROS and suggest that cytochrome oxidase may contribute to this O2 sensing.

Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions. Progress in biophysics and molecular biology , , ISSN:.

Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce.

In this study, we assess the ability of four human ventricular action potential models ten Tusscher and Panfilov, ; Grandi et al. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia.

Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia.

However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Hypoxia induces heart regeneration in adult mice. Nature , , — , DOI: Nakada, Yuji; Canseco, Diana C. Nature Publishing Group.

The adult mammalian heart is incapable of regeneration following cardiomyocyte loss, which underpins the lasting and severe effects of cardiomyopathy. Recently, it has become clear that the mammalian heart is not a post-mitotic organ. For example, the neonatal heart is capable of regenerating lost myocardium, and the adult heart is capable of modest self-renewal.

In both of these scenarios, cardiomyocyte renewal occurs via the proliferation of pre-existing cardiomyocytes, and is regulated by aerobic-respiration-mediated oxidative DNA damage. Therefore, we reasoned that inhibiting aerobic respiration by inducing systemic hypoxemia would alleviate oxidative DNA damage, thereby inducing cardiomyocyte proliferation in adult mammals.

Notably, we find that exposure to hypoxemia 1 wk after induction of myocardial infarction induces a robust regenerative response with decreased myocardial fibrosis and improvement of left ventricular systolic function. Genetic fate-mapping anal. These results demonstrate that the endogenous regenerative properties of the adult mammalian heart can be reactivated by exposure to gradual systemic hypoxemia, and highlight the potential therapeutic role of hypoxia in regenerative medicine.

Kubasiak, Lori A. National Academy of Sciences. Coronary artery disease leads to injury and loss of myocardial tissue by deprivation of blood flow ischemia and is a major underlying cause of heart failure.

Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and vascular cells; however, the mechanisms of ischemia-mediated cell death are poorly understood. Ischemia is assocd. We recently reported that hypoxia does not induce cardiac myocyte apoptosis in the absence of acidosis. We now report that hypoxia-acidosis-assocd.

Chronic hypoxia induced the expression and accumulation of BNIP3 mRNA and protein in cardiac myocytes, but acidosis was required to activate the death pathway. Acidosis stabilized BNIP3 protein and increased the assocn. Cell death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3 oligonucleotides.

The pathway included extensive DNA fragmentation and opening of the mitochondrial permeability transition pore, but no apparent caspase activation. Overexpression of wild-type BNIP3, but not a translocation-defective mutant, activated cardiac myocyte death only when the myocytes were acidic. This pathway may figure significantly in muscle loss during myocardial ischemia. Reversible alteration of calcium dynamics in cardiomyocytes during acute hypoxia transient in a microfluidic platform. Integrative Biology , 4 2 , — , DOI: Martewicz, S.

Royal Society of Chemistry. Heart disease is the leading cause of mortality in western countries. Apart from congenital and anatomical alterations, ischemia is the most common agent causing myocardial damage.

During ischemia, a sudden decrease in oxygen concn. The calcium handling machinery, which regulates the main functional features of a cardiomyocyte, is heavily compromised during acute hypoxic events.

Alterations in calcium dynamics have been linked to both short- and long-term consequences of ischemia, ranging from arrhythmias to heart failure. In this perspective, we aimed at investigating the calcium dynamics in functional cardiomyocytes during the early phase of a hypoxic event. For this purpose, we developed a microfluidic system specifically designed for controlling fast oxygen concn.

The obsd. Reversible alteration in ion channel function, that takes place in response to changes in cellular oxygen, might represent an adaptive mechanism of cardiopreservation during ischemia.

Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nature communications , 5 , ISSN:. Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive and large-scale intracellular recording.

It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes of a new geometry, namely nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow centre. We show that this nanotube geometry enhances cell-electrode coupling and results in larger signals than solid nanoelectrodes. The nanotube electrodes also afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording.

This study suggests that the nanoelectrode performance can be significantly improved by optimizing the electrode geometry. Reduction in number of sarcolemmal KATP channels slows cardiac action potential duration shortening under hypoxia. Zhu, Zhiyong; Burnett, Colin M. Elsevier B. The cardiovascular system operates under demands ranging from conditions of rest to extreme stress. KATP channel expression has a significant physiol. However, the effect of reduced channel expression on action potential duration shortening in response to severe metabolic stress is yet to be established.

Here, transgenic mice with myocardium-specific expression of a dominant neg. KATP channel subunit were compared with littermate controls. Evaluation of KATP channel whole cell current and channel no. Monophasic action potentials were monitored in retrogradely perfused, isolated hearts during the transition to hypoxic perfusate. Therefore, the no. Applied in vitro toxicology , 2 2 , ISSN: Cardiovascular diseases are prevalent worldwide and are the most frequent causes of death in the United States.

Particularly, adverse side effects to the heart and general vasculature have become common causes for preclinical project closures, and preclinical models do not fully recapitulate human in vivo dynamics. Recently, organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system-in particular, heart and general vasculature.

These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation. Heart- and vasculature-on-a-chip platforms have been successfully generated to study a variety of physiological phenomena, model diseases, and probe the effects of drugs.

Here, we review and discuss recent breakthroughs in the development of cardiovascular organs-on-a-chip platforms, and their current and future applications in the area of drug discovery and development. Progressive hypoxia-on-a-chip: An in vitro oxygen gradient model for capturing the effects of hypoxia on primary hepatocytes in health and disease. Oxygen is vital to the function of all tissues including the liver and lack of oxygen, i.

Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiol. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concns.

This range approx. Primary rat hepatocytes cultured in this microfluidic platform were exposed to an oxygen gradient of 0.

The establishment of an ascending hypoxia gradient in hepatocytes was confirmed in response to the decreasing oxygen supply. The hepatocyte viability in this platform decreased to approx.

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