• The release of Ca 2+ from intracellular stores through the inositol 1,4,5-trisphosphate receptor (InsP 3 R) occurs in both excitable and nonexcitable cells. (jneurosci.org)
  • The effects of endothelin-1 were compared with two other stimuli, isoproterenol and digoxin, which are known to induce inotropy and spontaneous Ca 2+ transients by overloading intracellular Ca 2+ stores. (biologists.com)
  • The various isoforms, arising by alternative splicing, mainly differ in the C-terminal intracellular tail [ 1 ] . (encyclopedia.pub)
  • This pathway leads to the Ca 2+ intracellular mobilization from internal stores and activation of protein kinase C (PKC) [ 1 ] . (encyclopedia.pub)
  • Scheme of the principal mGluR1 and mGluR5 signaling pathways, showing that G q/11 -dependent activation of phospholipase C β (PLCβ) mediates phosphatidylinositol hydrolysis with the generation of diacylglycerol (DAG) (that activates protein kinase C, PKC) and inositol-1,4,5-trisphosphate (IP 3 ) (that fosters Ca 2+ intracellular release from internal stores by acting on IP 3 R receptors on the endoplasmic reticulum). (encyclopedia.pub)
  • Application of endothelin 1 (ET-1), an agonist known to enhance synthesis of IP3, to quiescent lymphatic smooth muscle syncytia first enhanced spontaneous Ca2+ transients and/or intracellular Ca2+ waves. (edu.au)
  • We have studied changes of intracellular free calcium in cleavage- stage Xenopus embryos using fluorescent calcium indictor dyes, mainly Calcium Green-1. (elsevierpure.com)
  • We conclude that mouse proprioceptive sensory neurones are endowed with Ca 2+ - impermeable ionotropic P(2X) purinoreceptors and metabotropic P(2Y) purinoreceptors, which, by means of phospholipase C-drive inositol- trisphosphate (InsP 3 ) production, trigger the InsP 3 -induced Ca 2+ release from intracellular stores. (uaeu.ac.ae)
  • 5-HT and GABA provide negative paracrine feedback onto receptor cells by activating 5-HT1A and GABAA, GABAB receptors, respectively. (genome.jp)
  • Although ventricular cardiomyocytes express inositol 1,4,5-trisphosphate [Ins(1,4,5) P 3 ] receptors, it is unclear how these Ca 2+ channels contribute to the effects of Gq-coupled agonists. (biologists.com)
  • The endothelin-1-mediated spontaneous Ca 2+ transients were abolished by application of 2-aminoethoxydiphenyl borate (2-APB), an antagonist of Ins(1,4,5) P 3 receptors. (biologists.com)
  • ABSTRACT: A mathematical account is given of the processes governing the time courses of calcium ions (Ca2+), inositol 1,4,5-trisphosphate (IP(3)) and phosphatidylinositol 4,5-bisphosphate (PIP(2)) in single cells following the application of external agonist to metabotropic receptors. (physiomeproject.org)
  • For example, metabotropic mGluRs assemble into a macromolecular complex with IP3 receptors via the scaffolding protein Homer and co-purify with protein phosphatases and protein kinase A (PKA)1,4. (bioinbrief.com)
  • Ca2+ launch from internal stores in neurons is definitely controlled via the activation of phospholipase C (PLC), hydrolysis of phosphatidylinositol IMD 0354 tyrosianse inhibitor 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and activation of IP3 receptors located in the endoplasmic reticulum (ER), which leads to the launch of Ca2+ from your ER5. (bioinbrief.com)
  • Among these diverse features, it should be acknowledged that auto-antibodies toward glutamate receptors, GABA receptors, and K + channel-related proteins are preferentially found in autoimmune limbic encephalitis but not in IMCAs [ 10 ] (Table 1 ). (springer.com)
  • These peripheral cold receptors, both Aδ- and C-fibers, have thermal thresholds (i.e., the temperature at which nerve impulses are generated) for cold activation between 30-20°C, temperatures considered to be innocuously cool [ 4 , 6 ]. (nih.gov)
  • Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors. (jefferson.edu)
  • Regenerative and non-regenerative calcium transients in hamster eggs triggered by inositol 1,4,5-trisphosphate. (ox.ac.uk)
  • 1. Inositol 1,4,5-trisphosphate (InsP3) injected into unfertilized golden hamster eggs elicits a hyperpolarizing response (HR) that is due to stimulation of calcium-activated potassium channels in the egg plasma membrane. (ox.ac.uk)
  • 6. If large amounts of InsP3 were allowed to leak into the eggs constantly from a pipette, repetitive calcium transients were seen. (ox.ac.uk)
  • In addition, the extent of activation and desensitization of the receptor, using the calcium transients in cells initiated by exposure to agonist, is also predicted. (physiomeproject.org)
  • Cleavage formation was followed by calcium transients that localized to cleavage furrows and propagated along the furrows as calcium waves. (elsevierpure.com)
  • The calcium transients at the cleavage furrows were observed at each cleavage furrow at least until blastula stage. (elsevierpure.com)
  • For example, the mitochondrial movement in neurons is finely tuned to meet the local energy requirements and calcium buffering [ 4 ]. (biomedcentral.com)
  • Both effects of endothelin-1 were blocked by an antagonist of phospholipase C, suggesting that Ins(1,4,5) P 3 and/or diacylglycerol production was necessary. (biologists.com)
  • Canonical mGluRI signaling is driven by the G q /G 11 -dependent activation of phospholipase C β (PLCβ), inducing the hydrolysis of phosphoinositides and generation of inositol 1,4,5-trisphosphate (IP 3 ) and diacyl-glycerol (DAG). (encyclopedia.pub)
  • Globally, mGluRI can activate a multifaceted list of effectors, including phospholipase D (PLD), protein kinases pathways such as mitogen-activated protein kinase/extracellular receptor kinase (MAPK/ERK), the mammalian target of rapamycin (mTOR)/p70S6 kinase pathway, casein kinase 1, cyclin-dependent protein kinase 5, and Jun kinase (JUNK) [ 1 ] [ 2 ] ( Figure 1 ). (encyclopedia.pub)
  • Differential expression patterns of phospholipase D isoforms 1 and 2 in the mammalian brain and retina. (neurotree.org)
  • Actin modulating proteins that bind polyphosphoinositides, such as phosphatidylinositol 4, 5-bisphosphate (PIP2), can potentially participate in receptor signaling by restructuring the membrane cytoskeleton and modulating second messenger generation through the phosphoinositide cycle. (rupress.org)
  • Additional G protein-independent mechanisms involve the recruitment of β-arrestin or other scaffolding/adaptor proteins such as Homer long isoforms, that provide mGluRI coupling with other effectors, thus fostering activation of signaling pathways, such as the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K-Akt-mTOR) kinase pathway, or MEK1/2-ERK 1/2 pathway, both involved in mechanisms promoting protein synthesis. (encyclopedia.pub)
  • The mGluRI distinction from other mGluR groups (group II, including mGluR2 and mGluR3, and group III, comprising mGluR4, mGluR6, mGluR7, mGluR8) is based on amino-acid homology, agonist binding, and signaling pathways downstream to receptor activation [ 1 ] . (encyclopedia.pub)
  • In addition, depending on the cell-type and agonist 5-HT2A-Rs not merely stimulate the NOS3 Gq-PLC pathway, but various other pathways like the G12/13-PLA2 and Gi/o-Src pathway16C18 also. (bioinbrief.com)
  • mGluR1/5, through G q/11 -dependent mechanisms, also modulates ion channels, such as transient receptor potential channels (TRPCs), voltage-gated Ca 2+ channels (VGCC), and different types of K + channels (K v or SK), thus affecting neuronal excitability. (encyclopedia.pub)
  • For instance, activation of mGluR1 in neurons generates a single Ca2+ transient, whereas mGluR5 produces an oscillatory Ca2+ wave1,6. (bioinbrief.com)
  • The autoantigens include glutamic acid decarboxylase 65 (GAD65), voltage-gated Ca 2+ channel (VGCC), metabotropic glutamate receptor type 1 (mGluR1), and glutamate receptor delta (GluRdelta). (springer.com)
  • Incubation of electrically-paced ventricular myocytes with a membrane-permeant Ins(1,4,5) P 3 ester provoked the occurrence of spontaneous diastolic Ca 2+ transients with the same characteristics and sensitivity to 2-APB as the events stimulated by endothelin-1. (biologists.com)
  • In addition to evoking spontaneous Ca 2+ transients, stimulation of ventricular myocytes with the Ins(1,4,5) P 3 ester caused a positive inotropic effect. (biologists.com)
  • Fas receptor was activated by incubating NRVM with recombinant Fas ligand (rFasL, 50 ng/ml) and enhancing antibody (1 μg/ml), or by incubation of murine ventricular myocytes with the Fas-activating antibody Jo2 (10 μg/ml). (haifa.ac.il)
  • Further, voltage-gated Ca2+ channels are activated and release vesicular serotonin (5-HT), norepinephrine (NE) and gamma-aminobutyric acid (GABA). (genome.jp)
  • We show that W-7 acts on an acidic Ca 2+ -store: it abolished ATP-dependent vesicular acidification, inhibited V-type H + ATPase activity more potently than the weaker antagonist W-5 and caused vesicular Ca 2+ -leakage. (biomedcentral.com)
  • They form more circular dorsal membrane ruffles, have higher phosphoinositide turnover, inositol 1,4,5-trisphosphate generation and Ca2+ signaling. (rupress.org)
  • 2. A slow (0.5-4 Hz) membrane potential oscillation was observed in thalamocortical cells recorded in motor, sensory, associational and intralaminar thalamic nuclei. (researchgate.net)
  • 4. Anatomical or functional disconnection from related cortical areas resulted in a membrane potential hyperpolarization of about 9 mV and in the occurrence of spontaneous slow oscillations in virtually all recorded neurones. (researchgate.net)
  • 8. These results demonstrate that the majority of thalamocortical neurones are endowed with electrophysiological properties allowing them to oscillate at 0.5-4 Hz, if they have a membrane potential more negative than -65 mV and a high input resistance. (researchgate.net)
  • It has been suggested that improved activity of 5-HT2A-Rs might be responsible for some of the psychotic symptoms in schizophrenia14 and that atypical antipsychotic providers may antagonize the hyperactivity and membrane focusing on of 5-HT2A-Rs15. (bioinbrief.com)
  • Glucose-induced activation of DAG/PKC signaling in microsomes was not associated with a change in the translocation of Glut-4 transporters from microsomes to the plasma membrane, a biological response that is known to be stimulated by agonists, e.g., phorbol esters, which increase DAG/PKC signaling in plasma membranes, as well as in microsomes. (jci.org)
  • loop kappa p21 D cell 4( ABCD4) is shown to reduce the CD127 performance of cobalamin( Cbl membrane parking B12) into the mitochondrion, interacting it ED for the composition of Cbl lives. (evakoch.com)
  • However, FGFs 11-14, also known as FGF homologous factors 1-4 (FHF1-FHF4), have been shown to have distinct functional differences compared to the FGFs. (beauty104.com.tw)
  • Further we demonstrated that inhibition of transient transfection was due to iron (III) citrate particularly instead of citrate or iron only. (healthcarecoremeasures.com)
  • We conclude that the potentiation of cAMP relay by W-7 is due to a transient inhibition of the acidic Ca 2+ -store. (biomedcentral.com)
  • 1. Electrophysiologically identified thalamocortical neurones have been intra- and extracellularly recorded in acutely prepared cats, under different anaesthetic conditions. (researchgate.net)
  • 5. In contrast with other thalamic nuclei, the slow oscillation has not been observed in anterior thalamic neurones despite their having similar basic electrophysiological properties. (researchgate.net)
  • 5-HT also functions as a transmitter between presynaptic cells and the sensory afferent. (genome.jp)
  • Within this research an evaluation was performed of varied the different parts of a serum-free moderate employed for Chinese language hamster ovary cells where PEI-mediated transient transfection was inhibited. (healthcarecoremeasures.com)
  • Keywords: Transient transfection Polyethylenimine (PEI) Iron (III) citrate Recombinant proteins manifestation Monoclonal antibody Chinese language hamster ovary (CHO) cell range Introduction The usage of monoclonal antibodies for therapeutics offers risen dramatically before few years. (healthcarecoremeasures.com)
  • 2004). Currently most reports of transient transfection using PEI have used either HEK 293 or Chinese hamster ovary (CHO) cells (Derouazi et al. (healthcarecoremeasures.com)
  • A puzzling case is presented by cerebellar granule cells (GrC), the most numerous neurons of the brain 4 . (nature.com)
  • 5-HT2A-Rs are indicated on apical dendrites of cortical pyramidal neurons and cerebellar Purkinje cells. (bioinbrief.com)
  • Endothelin-1 augmented the amplitude of pacing-evoked Ca 2+ signals (positive inotropy), and caused an increasing frequency of spontaneous diastolic Ca 2+ -release transients. (biologists.com)
  • Among these, mechanically activated ion channels provide unique features: submillisecond response to mechanical stimuli, high sensitivity, large dynamic range, spatial coding of mechanical stimuli, and the ability to temporally filter repetitive stimuli 1 . (nature.com)
  • Generally, extracellular stimuli are converted in a transient increase in cytosolic Ca 2+ concentration, [Ca 2+ ] c , which, in turn, modulates cell function. (schoolbag.info)
  • Generally, extracellular stimuli are converted in a transient increase in the [Ca 2+ ] c , which, in turn, activates cellular functions. (schoolbag.info)
  • Eukaryotic cells are surrounded by media containing free Ca 2+ concentrations that exceed 1 mM, but they manage to maintain a free Ca 2+ concentration in the cytoplasm that is four orders of magnitude lower. (schoolbag.info)
  • The cytoplasmic Ca 2+ concentration ([Ca 2+ ](i)) was measured using indo-1 based microfluorimetry. (uaeu.ac.ae)
  • Repetitive nerve stimulation generally showed a transient increase of lumenal Ca 2+ in both the axon and presynaptic terminals. (frontiersin.org)
  • The TSEN placement Typically triggers 5' and 3' to the home', proliferating a downstream' vascular maturation on the 5' T and a 5' receptor nucleus on the 3' mitosis. (evakoch.com)
  • EphrinA1 treatment increased epithelial permeability, which was associated with decreased expression of ZO-1, ZO-2, and occludin. (bvsalud.org)
  • Despite this observation there have been reports of serum-free Benzoylpaeoniflorin medium used with both Benzoylpaeoniflorin 293 and CHO cells that allow levels of recombinant protein expression in the number of a huge selection of milligrams per liter with a recently available research confirming over 1?g/L of recombinant monoclonal antibody stated in 293 cells (Backliwal et al. (healthcarecoremeasures.com)
  • Activation of 5-HT2A has been associated with changes in spine and dendritic morphology8, changes in BDNF levels in the hippocampus and neocortex11 and normally results in an improved neuronal activity12,13. (bioinbrief.com)
  • This study showed for the first time that thrombin promotes specific, dose-dependent glutamate release from RPE cells, induced by the activation of protease-activated receptor 1 (PAR-1). (molvis.org)
  • In addition, mGluRI can activate several other pathways, and also G protein-independent mechanisms, by means of the interaction with specific adaptor proteins that recruit distinct signaling components [ 1 ] . (encyclopedia.pub)
  • Latest advances in transient transfection protocols using polyethylenimine (PEI) being a transfection reagent possess led to the introduction of cost-effective methods offering yields enough for commercial production of proteins for most preclinical needs. (healthcarecoremeasures.com)
  • These observations claim that modifications in 5-HT2A-R trafficking and G proteins signaling donate to the advancement and manifestation of neuropsychiatric disorders. (bioinbrief.com)
  • also, the 5' download volatility trading of the cytoplasm is involved actually by cationic end-product by the RNase proximity water cell, which has a direct RNA( RNA H1 in pathways) and at least 10 Fructose-6-phosphate nucleus( activated in Jarrous 2002, Xiao et al. (evakoch.com)
  • At 5 nM and above, InsP3 induced HRs with no detectable latency. (ox.ac.uk)
  • However, 100-fold greater InsP3 concentrations gave slow, larger Ca2+ transients (and HRs) with no detectable latency. (ox.ac.uk)
  • The latency and rise time of the transient are unaffected. (ox.ac.uk)
  • Unlike the sustained repetitive responses seen at fertilization, they were often smaller than the initial transient and less well sustained. (ox.ac.uk)
  • In brief, HT22 cells were grown in Dulbecco's modified Eagle's medium (DMEM) with high glucose and 1 mM sodium pyruvate (Mediatech), 2 mM Glutamax (Invitrogen), 5% bovine growth serum (BGS) (Hyclone) and penicillin-streptomycin (Mediatech). (biomedcentral.com)
  • Primary cultures of rat RPE cells were preloaded with 1 µCi/ml 3 H-glutamate in Krebs Ringer Bicarbonate (KRB) buffer for 30 min at 37 °C. Cells were rinsed and super-perfused with 1 ml/min KRB for 15 min. (molvis.org)
  • In contrast, blockade of L-type Ca2+ channels with nifedipine prevented ET-1 from inducing near-synchronous Ca2+ transients and resultant action potentials, leaving only asynchronous Ca2+transients and local Ca2+ waves. (edu.au)
  • In type III cells, sour taste is initiated when protons enter through apically located proton-selective ion channels: polycystic kidney disease 2-like 1 protein (PKD2L1) and polycystic kidney disease 1-like 3 protein (PKD1L3) channels. (genome.jp)
  • High level transient overexpression decreased actin filament staining in the center of the cells but not in the cell periphery. (rupress.org)
  • 1995). However CHO cells are used in most manufacturing cell lines and so it is desirable to use CHO cells for transient transfections to maintain the same post-translational modifications that would be found in the clinical or commercial product for applications that are sensitive to these modifications. (healthcarecoremeasures.com)
  • One of the most critical parameters affecting transient transfection efficiency is the medium in which the cells are grown. (healthcarecoremeasures.com)
  • 2008). With this research we have analyzed several different press for his or her compatibility with PEI-mediated transient transfection in CHO cells. (healthcarecoremeasures.com)
  • Not long after FGF1 and FGF2 were isolated, another group isolated a pair of heparin -binding growth factors which they named HBGF-1 and HBGF-2, whilst a third group isolated a pair of growth factors that caused proliferation of cells in a bioassay containing blood vessel endothelium cells which they called ECGF-1 and ECGF-2. (beauty104.com.tw)
  • Gad A, Callender DL, Killeen E, Hudak J, Dlugosz MA, Larson JE, Cohen JC, Chander A. Transient in utero disruption of cystic fibrosis transmembrane conductance regulator causes phenotypic changes in alveolar type II cells in adult rats. (jefferson.edu)
  • 4. The increase in [Ca2+]i in response to an initial injection of 1 nM InsP3 could be resolved into two distinct components: a slow, early rise immediately after InsP3 injection (phase I) followed by a larger and more rapid increase (phase II). (ox.ac.uk)
  • 5. Further injection of InsP3 resulted only in slow, smaller increases in [Ca2+]i that resembled phase I and often did not cause an HR. Phase II appeared to be absent. (ox.ac.uk)
  • However, a subsequent transient could still be elicited on injection of very large concentrations of InsP3. (ox.ac.uk)
  • It truly is identified that Ang II at low concentrations will not acutely impact neuronal excitability or smooth muscle cell reactivity but nevertheless impairs NVC,4 suggesting that astrocytes may perhaps play a central role within the acute Ang II nduced NVC impairment. (caspaseinhibitor.com)
  • By inhibiting the increase in NO at fertilization, we find not that the Ca(2+) transient is abolished but that the duration of the transient is significantly reduced. (ox.ac.uk)
  • Among them, ROCK1 (Rho-associated, coiled-coil containing protein kinase 1) and DIAPH1 (Diaphanous Homologue 1, a.k.a. hDia1, homologue to mDia1 in mouse, diaphanous in Drosophila) are the best described. (wikipedia.org)
  • 5-HT2A-Rs colocalize with PSD95 and MUPP1 (multi-PDZ website protein 1) in apical dendrites, dendritic shafts and spines8. (bioinbrief.com)
  • Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1,4,5-trisphosphate receptor mRNA. (okano-lab.com)
  • We tested the hypothesis that active inositol 1,4,5-trisphosphate receptor (IP3R)-operated Ca2+ stores interact as coupled oscillators to produce near-synchronous Ca2+ release events and associated pacemaker potentials, this driving action potentials and constrictions of lymphatic smooth muscle. (edu.au)
  • Seaweeds are extremely susceptible to microbial colonization due to the release of large amounts of carbon compounds that act as chemical attractants and nutrient sources for bacteria ( 1 ). (asm.org)
  • In Griscelli syndrome type 1, a defect in the myosin Va gene leads to the pigment dilution and neurological sequelae. (medscape.com)
  • [ 3 ] Griscelli syndrome type 1 is also thought to be the same entity or allelic to Elejalde syndrome, with ocular manifestations being prominent in Elejalde syndrome. (medscape.com)
  • Children with a defect in the MYO5A gene (Griscelli syndrome type 1) develop neurologic problems but no immunologic problems. (medscape.com)
  • Griscelli syndrome type 1 manifests with primary dysfunction of the CNS. (medscape.com)
  • In particular, one report describes a Griscelli syndrome type 1 patient alive at age 21 years with motor retardation and severe mental retardation and two patients with Griscelli syndrome type 3, healthy at ages 21 and 24 years, manifesting merely with silvery grey eyebrows, eyelashes, and hair, as well as pigmentary dilution in the skin. (medscape.com)
  • Griscelli syndrome type 2 can be classified with other familial causes of HLH (FHLH) such as Chédiak-Higashi syndrome type 1 (CHS1), Griscelli syndrome type 2, and X-linked lymphoproliferative (XLP) syndrome. (medscape.com)
  • Removal of extracellular Ca 2+ had no effect on both ATP-induced current and [Ca 2+ ](i) transient. (uaeu.ac.ae)
  • Auto-antibodies induced neurological diseases show various clinical phenotypes (see details in Table 1 ). (springer.com)
  • We conclude that NO is unlikely to be a primary egg activator but, rather, acts after the initiation of the Ca(2+) wave to regulate the duration of the fertilization Ca(2+) transient. (ox.ac.uk)
  • 1 - 1 ~-adfBnerglcagonlsts ,~, I POE inhibitors eAlP t AMP tachycardia dromotropic CHAPTER 1 {3-Blocking Agenl. (forexrin.com)
  • 1. Parameters derived from frequency-domain analysis of heart period and blood pressure variability are gaining increasing importance in clinical practice. (researchgate.net)
  • Figure 1 shows how the Ca 2+ /cAMP signaling interaction could be pharmacologically modulated by the combined use of the Ca 2+ channel blockers (CCB) and drugs that promote the increase of [cAMP] c (cAMP-enhancer compounds). (researchgate.net)
  • The major findings were that genistein prevented Fas-mediated increase in 1,4,5-IP 3 production in NRVM (quantified by ion-exchange chromatography): 216 ± 41 counts per minute (cpm) in control, 605 ± 184 cpm in FasL-treated cardiomyocytes and 137 ± 51 cpm in rFasL + genistein-treated cultures. (haifa.ac.il)
  • J Cell Biol (1995) 129 (1): 147-156. (rupress.org)
  • Journal of Cell Biology , 135 (1), 181-190. (elsevierpure.com)
  • However, potential pathogens were also previously detected on seaweed thalli and include microorganisms capable of degrading cell wall polysaccharides ( 5 - 7 ). (asm.org)
  • The ER was originally considered to be the sole dynamic Ca 2+ regulator in the cell, but it has now become clear that the nucleus, the mitochondria, the Golgi apparatus, the endosomes/lysosomes, and the secretory vesicles also play fundamental roles (Fig. 1). (schoolbag.info)
  • cAMP is secreted periodically after about 4 h of differentiation with a period length in cell suspension of about 7 min. (biomedcentral.com)
  • These two levels serve degraded by a phosphorylation including at least 6 membranes in a such tail that both leaves the 2' disorder ubiquitination and adducts the 3' heart to the 5' cell. (evakoch.com)
  • Correlation between Musashi-1 and c-hairy-1 expression and cell proliferation activity in the developing intestine and stomach of both chicken and mouse. (okano-lab.com)
  • The complexes heterozygous to HIV-1 are increased generally. (evakoch.com)
  • Larger near-synchronous Ca2+ transients then occurred leading to global synchronous Ca2+ transients associated with action potentials and resultant vasomotion. (edu.au)
  • Remarkably, the range of temperatures that these channels respond to covers the entire perceived temperature spectrum, from warm to painfully hot, from pleasingly cool to excruciatingly cold [ 1 ]. (nih.gov)