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Dekojová, Tereza, Lucie Houdová, Jiří Fatka, Pavel Pitule, Pavel Ostašov, Valentina S. Caputo, Hana Gmucová, Daniel Lysák, Pavel Jindra, and Monika Holubová. "Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study." Journal of Clinical Medicine 9, no. 11 (October 29, 2020): 3502. http://dx.doi.org/10.3390/jcm9113502.
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Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands—HLA(Human Leukocyte Antigen) class I molecules—are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients’ clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.
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Banerjee, A. K. "Ikiru." BMJ 343, no. 02 3 (November 2, 2011): d6993. http://dx.doi.org/10.1136/bmj.d6993.
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Kozyra, Agnieszka. "„Duchy osób żyjących” (ikiryō) jako treści nieświadomości w Kafce nad morzem Murakamiego Harukiego." Porównania 18 (November 1, 2016): 155–72. http://dx.doi.org/10.14746/p.2016.18.10589.
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Autorka analizuje motyw ikiryō, czyli ducha osoby żyjącej w powieściKafka nad morzem Murakamiego Harukiego starając się udowodnić, że odpowiada on różnym rodzajom treści nieświadomości zgodnie z psychoanalityczną typologią Gustava Junga. Motyw ikiryō występuje w mitologii i folklorze Japonii, a według Junga, baśnie, legendy czy mity wyrażają ekspresję psychicznych procesów nieświadomości zbiorowej i wraz z ideami religijnymi dostarczają symboli, z pomocą których treść nieświadomości może być skanalizowana do świadomości, a następnie zinterpretowana i zintegrowana. Autorka wykazuje, że ikiryō w powieści Murakamiego jest wieloznacznym pojęciem – stanowi bowiem zarówno archetyp Cienia, jak i wyparte traumatyczne treści nieświadomości indywidualnej. Murakami na przykładzie swojego bohatera, Kafki, ukazuje, że bez integracji tych treści nie jest możliwe funkcjonowanie silnej i odpowiedzialnej osobowości. Ikiryō są także związane z archetypem Cienia jako złem absolutnym, które nie jest abstrakcyjnym pojęciem, ale energią psychiczną związaną ze sferą emocji. Energia ta nie jest pod kontrolą podmiotowej świadomości, ale posiada pewną autonomię. Brak woli człowieka, by przeciwstawić się złu, które jest w nim samym, zostało najpełniej przejawione w archetypowym obrazie Cienia jako ikiryō, czyli duchu osoby żyjącej, nad którym jej ego nie ma żadnej kontroli.
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Dalva, Klara, Funda Gungor, Ender Soydan Akcaglayan, and Meral Beksac. "Two Independent Effects of Immunoglobulin-Like Receptor (KIR) Allele Matching between Siblings: Inhibitory KIR (iKIR) Mismatches Are Associated with Graft Versus Host Disease (GVHD) While Activatory KIR Matches (aKIR) and cGVHD Are Associated with Graft Versus Leukemia (GVL)." Blood 108, no. 11 (November 16, 2006): 2912. http://dx.doi.org/10.1182/blood.v108.11.2912.2912.
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Abstract Background: Activatory KIR receptors are observed less frequently than inhibitory KIRs (iKIR). Although the role of donor iKIRs and recipient ligands have been analyzed extensively, the effect of mismatches(mm) at aKIR or iKIR between donors(D) and recipients (R) have been addressed in only two studies (Gagne, Hum Immunol.2002 and Verheyden, Leukemia 2005 ): an aGVHD inducing effect of aKIR mm between unrelated donors and a protective effect of aKIRs: 2DS1 and 2DS2 against relapse were reported. The evaluation of other factors ie GVHD on GVL (related transplants) or GVL effects(MUD study) were lacking in these studies. Aim: In this prospective study we aimed to analyze the role of both D and R iKIR, aKIR and KIR-ligand match/mismatches on OS and DFS and made a multivariate comparison of all factors effecting outcome. Methods: A total of 79 patients with a median age of 34 (M/F: 42/37, AML/CML: 37/33, PBSCT/BMT: 59/20, sex mm: 49 %, ablative/nonablative conditioning: 63/16, BuCy: 72 %) transplanted from their HLA matched siblings. All D and R were typed for KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5a, 2DL5b, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL2, 3DS1) using the KIR Genotyping SSP Kit (Pel-Freeze, Dynal Biotech, USA). The frequency of GVHD was acute:44/76, chronic: 54/74. Statistical analysis were done using the SPSS 13.0 for Windows. The frequency of relapse in relation to m/mm at iKIR or aKIR alleles are summarized in table 1. Results: Overall KIR mm was observed in 75% of R-D pairs. 37 pairs had mm at the six iKIR loci (33% 2DL5a), 57 pairs had mm at the seven aKIR loci. The analysis on D iKIR/aKIR and the relevant R-ligand m/mm didnot reveal any effect on the frequency of GVHD or DFS. However when we compared the R and D KIR genotypes we were able to show a correlation between cGVHD and m vs mm at iKIR (62.5% vs 85%, p=0.041) and aGVHD ( 50% vs 67%) but not aKIR. The effect of aKIR mm was not influenced by stem cell source or diagnosis. Among the aKIR only 2DS5 and 3DS1, alone (20/30, 17/25 ) or together(16/21), resulted with more frequent aGVHD than pairs with other aKIRs (23/45). GVHD was associated with a decrease (aGVHD: p=0.032) or increase (cGVHD: p=0.076) in survival. cGVHD resulted with a decrease in relapse rate(−): 11/20 vs (+): 9/54: p=0.001). aKIRm was associated with an increase on DFS (p:0,031). Factors, other than KIR, known to influence outcome ie stem cell source, sex mismatch, conditioning regimen, disease type were analyzed in the multiple logistic regression and did not reveal any significant results. Conclusion: This study material enabled us to minimize the effect of HLA but PBSCT being the major source of stem cells potentiated the role of alloreactive T cells and cGVHD. Although only two of the donor aKIRs, 3DS1 and/or 2DS5 were associated with aGVHD, D-R match between all aKIR and cGVHD exerted a protective effect against relapse(0/15). Mismatching for iKIR was also associated with GVHD but GvL wasnot independent of GVHD. Thus, we may conclude that D-R aKIR, iKIR genotyping may help to predict GvL in related transplants. Frequency of relapse Stem Cell source aGVHD cGVHD PB n=59 BM n=20 (+) n=44 (−) n=32 (+) n=54 (−) n=20 aKIR m n=25 2/17 1/8 2/12 1/11 0/15 3/7 aKIR mm n=54 13/42 6/12 12/32 7/21 9/39 8/13 iKIR m n=44 10/31 4/13 8/21 6/21 4/25 9/15 iKIR mm n=35 5/28 3/7 6/23 2/11 5/29 2/5
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Kurosawa, Akira. "Ikiru [“To Live”]." Academic Medicine 76, no. 5 (May 2001): 437. http://dx.doi.org/10.1097/00001888-200105000-00014.
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Young-Mason, Jeanine. "Revisiting Kurosawaʼs Ikiru." Clinical Nurse Specialist 18, no. 1 (January 2004): 51–52. http://dx.doi.org/10.1097/00002800-200401000-00009.
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Sun, J. Y., A. Dagis, M. M. Miller, J. Longmate, R. Rodriguez, L. Gaidulis, S. J. Forman, and D. David. "Incompatible Inhibitory KIR Ligands Contribute To Lower Survival Rates in Leukemia Patients Receiving T-Replete Hematopoietic Cell Transplants (HCTs)." Blood 106, no. 11 (November 16, 2005): 2054. http://dx.doi.org/10.1182/blood.v106.11.2054.2054.
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Abstract Natural killer (NK) cells are becoming increasingly recognized as an important part of the immune system. Killer Ig-like receptors (KIRs) are the major form of receptors used by human NK cells. KIRs transmit either inhibitory or activating signals regulating NK cell activity. Some inhibitory KIRs specifically recognize HLA-A, B or -Cw allotypes on target cells. Thus differences in inhibitory ligand (iKIRL) phenotypes between donors and patients could result in NK cell alloreactivity that further results in different HCT outcomes. To test this hypothesis, the present study evaluated 362 patients with either ALL (99), AML/MDS (141), or CML (122). The patients were transplanted (1996~2003) with T-replete bone marrow, or peripheral blood stem cells from unrelated donors. High resolution HLA typing with DNA-based methods had been prospectively performed for donor selection. The KIR genes of patients and donors were retrospectively typed by a multiplex PCR-SSP method. The cohort was divided into three groups by the HLA and KIR profiles: 247 cases with matched HLA at the antigen level of HLA-A, B, Cw, DRB1, and DQB1 (MH), 64 with mismatched HLA (mMH) and 51 with mMH plus mismatched iKIRL (mMH+miKIRL). A significantly different rate (P=0.009) of estimated one year overall survival was found between the MH (61%, 95%CI 55–67%), the mMH (46%, 34–59%), and the mMH+miKIRL (29%, 18–43%) groups. When analyzing the event free survival, a similar difference (P=0.003) was observed between the MH (57%, 51–63%), the mMH (43%, 32–56%) and the mMH+miKIRL (25%, 15–39%) groups. Further analysis demonstrated a different rate (P=0.02) of relapse between the MH (two-year estimation: 21%, 16–28%), the mMH (16%, 7–31%), and the mMH+miKIRL (36% 18–58%) groups. That the MH group experienced more relapses than the mMH is consistent with the GvL effect. The mMH+miKIRL group experienced the most relapses implied miKIRL undermine the GvL effect. We also tested the influence of lacking iKIRL in patients within the MH group, and found a significant survival difference (P=0.05) among the patients lacking two iKIRLs (n=67, 54% 42%–65%), one iKIRL (n=104, 59% 49%–68%), or none (n=76, 70% 58%–79%). This finding contrasts with the previously reported beneficial role of potential NK cell alloreactivity in T-depleted HCT. Additional studies are required to resolve these issues.
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Handgretinger, Rupert, Peter Lang, and Maya C. André. "Exploitation of natural killer cells for the treatment of acute leukemia." Blood 127, no. 26 (June 30, 2016): 3341–49. http://dx.doi.org/10.1182/blood-2015-12-629055.
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Abstract Natural killer (NK) cells play an important role in surveillance and elimination of malignant cells. Their spontaneous cytotoxicity was first demonstrated in vitro against leukemia cell lines, and NK cells might play a crucial role in the therapy of leukemia. NK cell activity is controlled by an array of germ line–encoded activating and inhibitory receptors, as well as modulating coreceptors. This biologic feature can be exploited in allogeneic cell therapy, and the recognition of “missing-self” on target cells is crucial for promoting NK cell–mediated graft-versus-leukemia effects. In this regard, NK cells that express an inhibitory killer immunoglobulin-like receptor (iKIR) for which the respective major histocompatibility complex class I ligand is absent on leukemic target cells can exert alloreactivity in vitro and in vivo. Several models regarding potential donor–patient constellations have been described that have demonstrated the clinical benefit of such alloreactivity of the donor-derived NK cell system in patients with adult acute myeloid leukemia and pediatric B-cell precursor acute lymphoblastic leukemia after allogeneic stem cell transplantation. Moreover, adoptive transfer of mature allogeneic NK cells in the nontransplant or transplant setting has been shown to be safe and feasible, whereas its effectivity needs further evaluation. NK cell therapy can be further improved by optimal donor selection based on phenotypic and genotypic properties, by adoptive transfer of NK cells with ex vivo or in vivo cytokine stimulation, by the use of antibodies to induce antibody-dependent cellular cytotoxicity or to block iKIRs, or by transduction of chimeric antigen receptors.
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Ma, Yu-Ping, Jinjuan Cui, Hui-Juan Hu, and Zhuo-Hua Pan. "Mammalian Retinal Bipolar Cells Express Inwardly Rectifying K+ Currents (IKir) With a Different Distribution Than That of Ih." Journal of Neurophysiology 90, no. 5 (November 2003): 3479–89. http://dx.doi.org/10.1152/jn.00426.2003.
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Retinal bipolar cells comprise multiple subtypes that are well known for the diversity of their physiological properties. We investigated the properties and functional roles of the hyperpolarization-activated currents in mammalian retinal bipolar cells using whole cell patch-clamp recording techniques. We report that bipolar cells express inwardly rectifying K+ currents ( IKir) in addition to the hyperpolarization-activated cationic currents ( Ih) previously reported. Furthermore, these two currents are differentially expressed among different subtypes of bipolar cells. One group of cone bipolar cells in particular displayed mainly IKir. A second group of cone bipolar cells displayed both currents but with a much larger Ih. Rod bipolar cells, on the other hand, showed primarily Ih. Moreover, we showed that IKir and Ih differentially influence the voltage responses of bipolar cells: Ih facilitates and/or accelerates the membrane potential rebound, whereas IKir counteracts or prevents such rebound. The findings of the expression of IKir and the differential expression of Ih and IKir in bipolar cells may provide new insights into an understanding of the physiological properties of bipolar cells.
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Amarillo, Yimy, Angela I. Tissone, Germán Mato, and Marcela S. Nadal. "Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons." Journal of Neurophysiology 119, no. 6 (June 1, 2018): 2358–72. http://dx.doi.org/10.1152/jn.00867.2017.
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Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current IKir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of IKir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of IKir and hyperpolarization-activated cationic current Ih that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that IKir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with Ih and increases the robustness of low threshold-activated calcium current IT-mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current IKir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that IKir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current Ih; and increases the robustness of oscillations mediated by the low threshold-activated calcium current IT. Upregulation of IKir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).
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Stewart, Tessandra H., Clifford L. Eastman, Peter A. Groblewski, Jason S. Fender, Derek R. Verley, David G. Cook, and Raimondo D'Ambrosio. "Chronic Dysfunction of Astrocytic Inwardly Rectifying K+ Channels Specific to the Neocortical Epileptic Focus After Fluid Percussion Injury in the Rat." Journal of Neurophysiology 104, no. 6 (December 2010): 3345–60. http://dx.doi.org/10.1152/jn.00398.2010.
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Astrocytic inwardly rectifying K+ currents ( IKIR) have an important role in extracellular K+ homeostasis, which influences neuronal excitability, and serum extravasation has been linked to impaired KIR-mediated K+ buffering and chronic hyperexcitability. Head injury induces acute impairment in astroglial membrane IKIR and impaired K+ buffering in the rat hippocampus, but chronic spontaneous seizures appear in the perilesional neocortex—not the hippocampus—in the early weeks to months after injury. Thus we examined astrocytic KIR channel pathophysiology in both neocortex and hippocampus after rostral parasaggital fluid percussion injury (rpFPI). rpFPI induced greater acute serum extravasation and metabolic impairment in the perilesional neocortex than in the underlying hippocampus, and in situ whole cell recordings showed a greater acute loss of astrocytic IKIR in neocortex than hippocampus. IKIR loss persisted through 1 mo after injury only in the neocortical epileptic focus, but fully recovered in the hippocampus that did not generate chronic seizures. Neocortical cell-attached recordings showed no loss or an increase of IKIR in astrocytic somata. Confocal imaging showed depletion of KIR4.1 immunoreactivity especially in processes—not somata—of neocortical astrocytes, whereas hippocampal astrocytes appeared normal. In naïve animals, intracortical infusion of serum, devoid of coagulation-mediating thrombin activity, reproduces the effects of rpFPI both in vivo and at the cellular level. In vivo serum infusion induces partial seizures similar to those induced by rpFPI, whereas bath-applied serum, but not dialyzed albumin, rapidly silenced astrocytic KIR membrane currents in whole cell and cell-attached patch-clamp recordings in situ. Thus both acute impairment in astrocytic IKIR and chronic spontaneous seizures typical of rpFPI are reproduced by serum extravasation, whereas the chronic impairment in astroglial IKIR is specific to the neocortex that develops the epileptic focus.
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Pączkowska, Agnieszka. "Zjawisko ikiryō jako przykład podróży dusz w japońskiej literaturze dworskiej (VIII-XII wiek)." Studia Azjatystyczne 1, no. 1 (December 1, 2015): 115. http://dx.doi.org/10.14746/sa.2015.1.08.
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Oleskevich, S. "G alpha o1 decapeptide modulates the hippocampal 5-HT1A potassium current." Journal of Neurophysiology 74, no. 5 (November 1, 1995): 2189–93. http://dx.doi.org/10.1152/jn.1995.74.5.2189.
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1. The serotonin1A (5-HT1A) receptor is coupled to an inwardly rectifying potassium current (IKir) via a G protein. The identity of the G-protein subtype was investigated with 2 10-amino acid peptides derived from the carboxyl (C) terminus of the alpha-subunits of the Go1 and Gi2 proteins (G alpha o1 and G alpha i2). The synthetic decapeptides were applied by intracellular perfusion during whole cell recording from dentate granule cells in the hippocampal slice preparation. 2. Bath application of 5-HT produced an IKir, which was blocked by the selective 5-HT1A receptor antagonist, pindobind5-HT1A. The G alpha o1 peptide inhibited the 5-HT1A IKir by 60 +/- 7% (mean +/- SE; t = 30 min), whereas the G alpha i2 peptide had no effect. The G alpha o1 peptide produced a slowly developing outward current that was not observed in the absence of peptide or in the presence of the G alpha i2 peptide. 3. The results indicate that G alpha o1 and not G alpha i2 modulates the 5-HT1A IKir in hippocampal granule cells. They also suggest that G alpha o1 occludes the 5-HT1A response by direct activation of the IKir. The intracellular perfusion of synthetic G alpha peptides provides a new approach to identify the G-protein subtype(s) in a receptor-mediated electrophysiological response.
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He, Jun, Zi-xing Chen, Xiao-jing Bao, De-pei Wu, Xiao-ni Yuan, Ai-ning Sun, Li Yao, Jian-nong Cen, and Qiao-cheng Qiu. "Impact of the Inhibitory KIR-HLA Receptor-Ligand Model on Unrelated Hematopoietic Stem Cell Transplantation in Patients with Leukemia." Blood 110, no. 11 (November 16, 2007): 5063. http://dx.doi.org/10.1182/blood.v110.11.5063.5063.
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Abstract The interaction between killer cell immunoglobin-like receptor (KIR) and HLA molecule has particular relevance to the unrelated hematopoietic stem cell transplantation (HSCT). The presence of KIR on donor’s NK cells and the absence of the corresponding KIR ligand in the recipient’s HLA repertoire as a receptor-ligand model can be used to predict the outcome of HSCT. To investigate the effect of KIR-HLA receptor-ligand mismatching and the expression of inhibitory KIR (iKIR) on the unrelated Allo-HSCT of leukemia, the following study has been carried out. The KIR genotypes of 36 patients of ALL (n=18), AML (n=10), and CML (n=8) as well as their unrelated donors were obtained from the Database of China Marrow Donor Program. KIR genotyping was performed with PCR-SSP. The KIR and HLA mismatching status (receptor-ligand mismatch model) between recipients and donors was analyzed thereafter. The expression of iKIR was determined by flow cytometry on recipients after HSCT. All cases were followed up closely until July, 2007. Among all the donor/recipient pairs analyzed, 15 pairs displayed the matched pattern with respect to the KIR genotyping though, graft-versus-host (GVH) KIR ligand-mismatched in 13 pairs, and host-versus-graft (HVG) KIR ligand-mismatched in 8 pairs. 26 recipients were lack of HLA-Cw2,4,5,6,15 ligands although iKIR/2DL1 was expressed on their corresponding donors. Similarly, 35 donors with iKIR/2DL2/L3 on their NK cells could recognized HLA- Cw1,3,7,8,12,14 ligands in their recipients. iKIR/3DL1 was expressed on 9 donors although the correlated HLA-Bw4 ligand was absent on the recipients. iKIR/3DL2 was expressed on 24 donors although the correlated HLA-A11 ligand was absent on the recipients. Except for one case, 35 patients were successfully transplanted, in which seven patients were dead, giving the survival rate of 80.0%. The cause of death was either acute/chronic GVHD or relapse. The frequency of acute GVHD (60.0%, 9/15), leading to death (26.7%, 4/15), was the highest in KIR receptor-ligand matched model. The incidence of acute GVHD and death was 30.8% (4/13) and 23.1% (3/13) in the GVH KIR ligand-mismatching, respectively; while the incidence of chronic GVHD was 37.5% (3/8) and no death happened in HVG KIR ligand-mismatching pattern. The expression of iKIR/2DL1 could be detected on ALL (13.0%∼16.6%) and CML (1.8∼6.2%) patients four month after HSCT. The expression of both iKIR/2DL1 (4%) and iKIR/2DL2 (12%) was found only in one patient with CML three month after HSCT, increased to 33.4% and 32.6% accompanied by cGVHD, and dropped to 7.6% and 10.3% one year after HSCT. These results suggested that the deficiency in iKIR/2DL1 based on the KIR-HLA receptor-ligand mismatching model together with the expression of a number of activating KIR in recipients increases the occurrence of GVHD, relapse, and death in unrelated HSCT. Analysis on KIR-HLA gene expression profiling could be useful in predicting the clinical outcome of unrelated Allo-HSCT in leukemia patients. The overall and disease-free survival after HSCT could be improved by preventing the development of GVHD.
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Tao, Rong, Chu-Pak Lau, Hung-Fat Tse, and Gui-Rong Li. "Functional ion channels in mouse bone marrow mesenchymal stem cells." American Journal of Physiology-Cell Physiology 293, no. 5 (November 2007): C1561—C1567. http://dx.doi.org/10.1152/ajpcell.00240.2007.
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Bone marrow mesenchymal stem cells (MSCs) are used as a cell source for cardiomyoplasty; however, the cellular electrophysiological properties are not fully understood. The present study was to investigate the functional ionic channels in undifferentiated mouse bone marrow MSCs using whole cell patch-voltage clamp technique, RT-PCR, and Western immunoblotting analysis. We found that three types of ionic currents were present in mouse MSCs, including a Ca2+-activated K+ current ( IKCa), an inwardly rectifying K+ current ( IKir), and a chloride current ( ICl). IKir was inhibited by Ba2+, and IKCa was activated by the Ca2+ ionophore A-23187 and inhibited by the intermediate-conductance IKCa channel blocker clotrimazole. ICl was activated by hyposmotic (0.8 T) conditions and inhibited by the chloride channel blockers DIDS and NPPB. The corresponding ion channel genes and proteins, KCa3.1 for IKCa, Kir2.1 for IKir, and Clcn3 for ICl, were confirmed by RT-PCR and Western immunoblotting analysis in mouse MSCs. These results demonstrate that three types of functional ion channel currents (i.e., IKir, IKCa, and ICl) are present in mouse bone marrow MSCs.
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Kasamon, Yvette L., Leo Luznik, M. Sue Leffell, Hua-ling Tsai, Heather J. Symons, Javier Bolaños-Meade, Gary Rosner, et al. "Significance of Missing Inhibitory KIR Ligands in Nonmyeloablative, HLA-Haploidentical (Haplo) BMT with Posttransplantation High-Dose Cyclophosphamide (PT/Cy)." Blood 118, no. 21 (November 18, 2011): 840. http://dx.doi.org/10.1182/blood.v118.21.840.840.
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Abstract Abstract 840 Significance of Missing Inhibitory KIR Ligands in Nonmyeloablative, HLA-Haploidentical (Haplo) BMT with Posttransplantation High-Dose Cyclophosphamide (PT/Cy). Yvette L. Kasamon 1, Leo Luznik1, Mary S. Leffell1, Hua-Ling Tsai1, Heather J. Symons1, Javier Bolaños-Meade1, Gary Rosner1, Lawrence E. Morris2, Pamela A. Crilley3, Richard J. Jones1 and Ephraim J. Fuchs1, (1)Johns Hopkins University, Baltimore, MD, (2)Northside Blood and Marrow Transplant Program, Atlanta, GA, (3)Hahnemann University Hospital, Philadelphia, PA Introduction: NK cells can influence haplo BMT outcomes including risks of relapse and GVHD. Our group previously reported that, in allogeneic BMT for hematologic malignancies that incorporates PT/Cy, donor-recipient iKIR (inhibitory killer-cell immunoglobulin-like receptor) gene mismatches and having a KIR haplotype B donor were associated with improved outcomes (BBMT 2010;16:533). Because the reported impact of NK cell alloreactivity models in haplo BMT has been variable and some models are relevant to donor selection, we expanded our analysis of iKIR ligand status in this transplantation platform. Patients and methods: Outcomes of 212 uniformly treated patients (pts) enrolled on two similar clinical trials of related-donor, haplo BMT were retrospectively analyzed. Planned treatment consisted of fludarabine (30 mg/m2 IV on days −6 to −2), Cy (14.5 mg/kg IV on days −6 and −5), total body irradiation (200 cGy on day −1), and non-T-cell depleted bone marrow infusion. GVHD prophylaxis consisted of high-dose Cy (50 mg/kg IV on days 3 and 4), mycophenolate mofetil on days 5–35, and tacrolimus on days 5–180 without taper, with filgrastim begun on day 5. All pts (median age 51, range 1–73) had poor-risk hematologic malignancies; 60 (28%) had prior BMT. Diagnoses were Hodgkin lymphoma (31 pts), NHL (69), CLL (21), multiple myeloma (6), acute leukemia or lymphoblastic lymphoma (62), MDS (9), CML (9), CMML (4), PV (1). Missing ligands (ML; defined as absence in the recipient of one or more HLA ligands for iKIRs) and donor/recipient iKIR ligand incompatibility (LI; defined as presence of an iKIR ligand in the donor that is absent in the recipient) were determined using high-resolution HLA typing of class I alleles. For study purposes, HLA-A*2301, A*2402, and A*3201 were included in the Bw4 serologic group and effects attributable to HLA-A3 and A11 ligand groups were excluded. Results: With a median 2.9 year follow-up (range, 0.3–7 years) in pts without events, the actuarial 2-year progression-free survival (PFS) was 34%. On competing-risk analysis, cumulative incidences of grade II–IV acute GVHD and chronic GVHD were 28% and 14%, respectively; 1-year cumulative incidences of relapse and nonrelapse mortality (NRM) were 42% and 14%. Baseline characteristics in pts with ML (157 pts, of whom 76 had LI) and without ML were similar. On univariate analysis, pts with LI had no significant difference in PFS (figure A), grade II–IV acute GVHD, relapse or NRM compared to those without LI. In contrast, as compared to no ML, the presence of ML was associated with a statistically significantly improved PFS on univariate analysis (hazard ratio [HR] = 0.68, p = 0.03; figure B). This association was not identified in our previous analysis, potentially due to underpowering or inclusion of pts receiving one dose of PT/Cy. No statistically significant difference was detected according to the presence or absence of ML in the cumulative incidences of acute GVHD, relapse, or NRM, although presence of ML was associated with a tendency toward lower NRM risk (HR = 0.61, p = 0.17). On multivariate analysis, the presence of ML was found to be independently associated with a significant improvement in PFS (HR = 0.66, p = 0.03). This multivariate model also confirmed our previous observation (BBMT 2010;16:482) that greater donor-recipient HLA disparity was not detrimental to PFS (HR = 0.57, p = 0.04 for 3–4 antigen mismatches versus fewer at HLA-A, B, C, and DRB1 combined). We are currently investigating the impact of KIR haplotypes in this setting with the goal of optimizing donor selection. Conclusion: The presence of ML may be beneficial in haplo BMT with postgrafting immunosuppression that includes high-dose Cy. Further studies are needed to confirm and define the mechanisms of this effect. Our findings do not support selection of donors on the basis of LI in this transplantation platform. Disclosures: No relevant conflicts of interest to declare.
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Wolfgang, Wagner. "Cancer and the arts: the fight for meaning – Akira Kurosawa’s "Ikiru"." ESMO Open 2, Suppl 1 (February 2017): e000131. http://dx.doi.org/10.1136/esmoopen-2016-000131.
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Nanzatov, B. Z., and V. V. Tishin. "Toward Buryat-Yakut Ethnic Connections: İgidäi and Eχirid." Bulletin of the Irkutsk State University. Geoarchaeology, Ethnology, and Anthropology Series 32 (2020): 26–36. http://dx.doi.org/10.26516/2227-2380.2020.32.26.
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The formation of the Yakut people is associated with the several waves of migration from the southern direction, in which Mongol-speaking communities took part. The researchers of the Yakuts ethnic history noticed the ethnonym İgidäi, known as the name of a large tribal group in the interfluve of Aldan and Lena Rivers, in the 17th century, which was connected in Russian written sources with the particular unit are “Igideiskaya volost”. In the late 19th century the descendants of this population were presented by four administrative units (nasleg) in the Bayagantai and Baturus ulus (as 1st and 2nd Igideysky in both cases). There is no association in the names of the smaller administrative units (Russian: rod) attested as parts of these nasleg with other ethnonyms. This suggests that those populations were quite homogeneous and did not subject to large external migrations in the historical period. By itself, the ethnonym İgidäi was repeatedly associated with the name of a large tribal grouping of Western Buryats, known as eχirid (rus. ekhirit), which in turn goes back to the Middle Mongolian ethnonym Ikires. Pprevious researchers had outlined right path of searching, however they limited only a statement of the formal consonance of the Yakut İgidäi and buryats eχirid. The present article is devoted to the argumentation of the comparison based on the analysis of phonetic data. The form İgidäi make it possible to reconstruct the primary appearance of the ethnonym as *ikir (plur.: ikid), which correlates with the dialectal version of the Western Buryat ethnonym attested as eχirši, also referring to the early form *ikir. The tribe Ikires mentioned above was known in the 13–14th centuries and was associated with the territory of Mongolia. Information about the Ekhirits, because of lack of written sources, attested only in the 17th century AD in the Western Baikal region. Despite the obvious kinship of their names, it is not possible to trace any intermediate stages that would allow us to talk about the unity of the history of the population known by these ethnonyms. At the same time, the identification among the Yakuts the ethnonym, which clearly goes back to the form that demonstrates the phonetic characteristics of Western Buryat dialects, allows us, based on the general historical context, to move the lower chronological border beginning the stay of the ethnonym Eχirid carriers in the Western Baikal region at least by a century.
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Adebowale, T. K., O. O. Oduntan, A. E. Adegbenjo, and A. S. Akinbode. "Economic Contribution of Wildlife to Bushmeat Market in Ikire, Osun State, Nigeria." Journal of Applied Sciences and Environmental Management 25, no. 4 (October 8, 2021): 579–83. http://dx.doi.org/10.4314/jasem.v25i4.14.
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This paper assessed the economic contribution of wildlife to bushmeat market in Ikire, Osun State, Nigeria. Primary data were collected using semi-structured questionnaire and in-depth interview of targeted respondents. Bush meat sellers in Irewole local government area, Ikire were sampled. Data were analyzed using descriptive statistics, budgetary analysis and likert scale analysis. The result showed that majority of the bushmeat sellers were females (55.9%) with a mean age of 41 years. Most of the bushmeat sellers strongly agreed (4.91±0.09) that they generate more income from bushmeat trade, 4.71±0.17 equally noted that customers prefer to purchase bushmeat than convectional meat type while 1.56±0.19 disagreed that seasonal change affects customer’s preferences for bushmeat in the markets. Also, 5.00±0.0, 4.82±0.13, 4.74±0.17 respectively believes that bushmeat are more delicious, better source of protein, more of medicinal value when compared with conventional meat type. Furthermore, an average of 3.70±0.2 had cultural sentiments for the consumption of bush meat. An average net profit per respondent yielded ₦3,565.53, while BCR and profitability index are 1.95 and 0.95 respectively. Conclusively, bushmeat trading is a profitable and very lucrative enterprise.
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Lorna Fitzsimmons. "Faustian Reparation in Ikiru and Eternity and a Day." Goethe Yearbook 11, no. 1 (2002): 347–72. http://dx.doi.org/10.1353/gyr.2011.0039.
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Han, Yi, Jia-Dao Chen, Zu-Mei Liu, Yuan Zhou, Jia-Hong Xia, Xin-Ling Du, and Man-Wen Jin. "Functional ion channels in mouse cardiac c-kit+ cells." American Journal of Physiology-Cell Physiology 298, no. 5 (May 2010): C1109—C1117. http://dx.doi.org/10.1152/ajpcell.00207.2009.
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Cardiac c-kit+ cells are generally believed to be the major population of stem/progenitor cells in the heart and can be used as a cell source for cardiomyoplasty; however, the cellular electrophysiological properties are not understood in this type of cells. The present study was designed to investigate functional ion channels in undifferentiated mouse cardiac c-kit+ cells using approaches of whole cell patch voltage clamp, RT-PCR, and cell proliferation assay. It was found that three types of ionic currents were present in mouse cardiac c-kit+ cells, including a delayed rectifier K+ current (IKDR) inhibited by 4-aminopyridine (4-AP), an inward rectifier K+ current ( IKir) decreased by Ba2+, and a volume-sensitive chloride current ( ICl.vol) inhibited by 5-nitro-1-(3-phenylpropylamino) benzoic acid (NPPB). RT-PCR revealed that the corresponding ion channel genes, Kv1.1, Kv1.2, and Kv1.6 (for IKDR), Kir.1.1, Kir2.1, and Kir2.2 (likely responsible for IKir), and Clcn3 (for ICl.vol), were significant in mouse cardiac c-kit+ cells. The inhibition of ICl.vol with NPPB and niflumic acid, but not IKDR with 4-AP and tetraethylammonium, reduced cell proliferation and accumulated the cell progression at G0/G1 phase in mouse cardiac c-kit+ cells. Our results demonstrate that three types of functional ion channel currents (i.e., IKDR, IKir, and ICl.vol) are present in mouse cardiac c-kit+ cells, and ICl.vol participates in regulating cell proliferation.
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Isitman, Gamze, Alexandra Tremblay-McLean, Irene Lisovsky, Julie Bruneau, Bertrand Lebouché, Jean-Pierre Routy, and Nicole F. Bernard. "NK Cells Expressing the Inhibitory Killer Immunoglobulin-Like Receptors (iKIR) KIR2DL1, KIR2DL3 and KIR3DL1 Are Less Likely to Be CD16+ than Their iKIR Negative Counterparts." PLOS ONE 11, no. 10 (October 12, 2016): e0164517. http://dx.doi.org/10.1371/journal.pone.0164517.
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Judge, S. I., E. Montcalm-Mazzilli, and E. K. Gallin. "IKir regulation in murine macrophages: whole cell and perforated patch studies." American Journal of Physiology-Cell Physiology 267, no. 6 (December 1, 1994): C1691—C1698. http://dx.doi.org/10.1152/ajpcell.1994.267.6.c1691.
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Previous studies have reported that the inwardly rectifying K+ conductance (GKir) in macrophages is modulated by intracellular perfusion with inositol 1,4,5-triphosphate (InsP3), inositol 1,3,4,5-tetrakisphosphate (InsP4), or GTP analogues and by exposing cells to macrophage-specific colony-stimulating factor (CSF) I. This study uses both conventional whole cell and amphotericin B perforated patch studies to investigate GKir modulation in thioglycollate-elicited mouse peritoneal macrophages (MO). Under whole cell recording conditions with 150 mM Cl- in the patch pipette, GKir decreased within 25 min. The GKir decrease was slowed by exchanging glutamate for Cl- as the major anion in the pipette or by adding guanosine 5'-O-(2-thiodiphosphate) (50 nM) or ATP (0.5 mM) to the pipette. Addition of InsP3 or InsP4 to the pipette had no effect on the magnitude of GKir or its rate of decrease but activated an outward current in the voltage range of +60 to +120 mV in 57% of the cells studied. Thus in murine MO GKir may be modulated by G proteins but is unaffected by inositol phosphate metabolites, which have been reported to enhance GKir in phorbol 12-myristate 13-acetate (PMA)-differentiated HL-60 cells. In contrast to whole cell studies, perforated patch recordings of murine MO GKir were stable for > 1 h. Perforated patch studies demonstrated that murine MO also differ from PMA-differentiated HL-60 cells in that CSF I had no effect on GKir. Additionally, arachidonic acid, PMA, and H2O2, agents implicated in macrophage activation, did not modulate GKir. We conclude that GKir regulation in murine MO differs from that reported in PMA-differentiated HL-60 cells and that although our data suggest that GKir is modulated by G protein(s), they differ from the G proteins involved in MO responses to CSF I and the other agents tested.
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Travagli, R. A., and R. A. Gillis. "Hyperpolarization-activated currents, IH and IKIR, in rat dorsal motor nucleus of the vagus neurons in vitro." Journal of Neurophysiology 71, no. 4 (April 1, 1994): 1308–17. http://dx.doi.org/10.1152/jn.1994.71.4.1308.
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1. The patch-clamp technique applied to the in vitro thin brain slice preparation was used to record voltage and current traces from visually identified neurons of the rat dorsal motor nucleus of the vagus (DMV). 2. The majority of DMV neurons (102 of 159, i.e., 64%) showed a slowly developing hyperpolarization-activated current that had its threshold generally positive to resting potential and that exhibited a half-maximal activation at -90 mV and full saturation at -127 mV. The activation time constant was strongly voltage dependent, decreasing with hyperpolarization. 3. Ion substitution experiments identified the hyperpolarization-activated current as IH. In fact, the current was potassium- and sodium-sensitive. Raising the extracellular potassium concentration from 3.75 to 20 mM increased the current peak amplitude in a voltage-dependent manner, whereas lowering extracellular sodium concentration from 146 to 26 mM decreased the current peak amplitude with a shift of the activation threshold toward more hyperpolarized potentials. The IH was significantly reduced during perfusion with either external cesium or rubidium but was insensitive to barium and tetraethylammonium (TEA). 4. A subset of DMV neurons (44 of 159, i.e., 28%) showed the presence of fast inward rectification but no IH. The current was activated at potentials close to the potassium equilibrium potential and reached steady state within 10 ms from the onset of the hyperpolarizing step. 5. Ion substitution experiments identified this hyperpolarization-activated current as IKIR. In fact, the current was potassium sensitive; its activation curve shifted toward less negative potentials with increasing potassium concentrations. IKIR was sodium insensitive, being unaffected by the lowering of the external sodium concentration. IKIR was significantly reduced during perfusion with cesium, barium, and TEA. 6. In the DMV neuronal subpopulation expressing IH, the IH contribution to the total cell conductance was approximately 30% at -87 to -97 mV. Furthermore, the same subpopulation of neurons was hyperpolarized in a voltage-related manner on perfusion with 5 mM cesium: at -57 mV, cesium induced a hyperpolarization of 5.6 +/- 1.3 (SE) mV, whereas at -72 mV the cesium-induced hyperpolarization was 26 +/- 4.4 mV. 7. Perfusion with 5 mM cesium reduced the spontaneous firing rate of a subset of neurons exhibiting IH but cesium never decreased the firing rate of neurons exhibiting IKIR.(ABSTRACT TRUNCATED AT 400 WORDS)
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Garrett, Tyrel. "A phenomenological reflection on Kurosawa's Ikiru in light of the early Heidegger's concept of “distance”." Humanistic Psychologist 43, no. 3 (2015): 310–16. http://dx.doi.org/10.1080/08873267.2015.1062013.
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Machado-Sulbaran, Andrea Carolina, María Guadalupe Ramírez-Dueñas, José Eduardo Navarro-Zarza, José Francisco Muñoz-Valle, Francisco Mendoza-Carrera, Christian Johana Baños-Hernández, Isela Parra-Rojas, Margarita Montoya-Buelna, and Pedro Ernesto Sánchez-Hernández. "KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico." Journal of Immunology Research 2019 (January 6, 2019): 1–11. http://dx.doi.org/10.1155/2019/6808061.
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Introduction. Systemic Sclerosis (SSc) is an autoimmune, inflammatory, and multisystemic disease characterized by the presence of autoantibodies and fibrosis. The pathogenesis involves the interaction between immune system cells such as macrophages, NK cells, T cells, and B cells. Killer-cell Immunoglobulin-like Receptors (KIR) are expressed in NK cells and some T cell subsets that recognize HLA class I molecules as ligands and are involved in regulating the activation and inhibition of these cells. The KIR family consists of 14 genes and two pseudogenes; according to the gene content, the genotype could be AA and Bx. The aim of this study was to evaluate the association between KIR/HLA genes and genotypes with SSc and the clinical characteristics. Methods. We included 50 SSc patients and 90 Control Subjects (CS). Genotyping of KIR, HLA-C, -Bw4, and -A∗03/∗11 was made by SSP-PCR. Results. In SSc patients, a higher frequency of KIR2DL2 (p=0.0007, p′=0.011), KIR2DS4del (p=0.001, p′=0.021), and HLA-C2 (p=0.02, p′=0.09) was found. This is the first study to evaluate the frequency of HLA-A∗03/∗11 in SSc patients, of which a low frequency was found in both groups. Compound genotypes KIR2DL2+/HLA-C1+ or KIR2DL2+/HLA-C2+ have a higher frequency in SSc patients. The Bx genotype was the most frequent and was associated with risk to SSc (p=0.007, OR=3.1, 95% CI=1.4–7.9, p′=0.014). The genotypes with a higher iKIR number than aKIR (iKIR>aKIR) were found in all individuals; genotypes with 7-8 iKIR genes were increased in SSc patients. We do not find an association between the KIR genes with the clinical characteristics. Conclusion. The results suggest that KIR2DL2 and 2DS4del could have a risk role in the development of SSc, but not with clinical manifestations.
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Solomon, Scott R., Michael T. Aubrey, Xu Zhang, Katelin C. Jackson, Christina L. Roark, Brian M. Freed, Lawrence E. Morris, H. Kent Holland, Asad Bashey, and Melhem Solh. "Recipient HLA-B Leader Genotype, and Its Relationship to Total KIR Missing Ligand, Informs Relapse and Survival Following Haploidentical Transplantation Using Post-Transplant Cyclophosphamide." Blood 138, Supplement 1 (November 5, 2021): 418. http://dx.doi.org/10.1182/blood-2021-151496.
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Abstract In addition to donor T cells, natural killer (NK) cells are proposed to play a significant role in the graft-versus-leukemia (GVL) effect following haploidentical donor transplantation (HIDT). Following HIDT, donor NK cells express activating (NKG2C) receptors (Ciurea, Leukemia 2021), whose ligand is the non-classical human leukocyte antigen, HLA-E. For surface expression, HLA-E requires binding of leader peptides derived from class I HLA molecules. The rs1050458C/T dimorphism at position -21 of exon 1 of HLA-B gives rise to leader peptides with either methionine (M) or threonine (T) at the second residue of the processed leader peptide. M-containing HLA-B leader peptides promote higher HLA-E expression than T-leaders, potentially favoring more robust natural NK cell recognition of HLA-E-expressing tumor cells. Alternatively, donor NK cells can be activated through inhibitory killer cell immunoglobulin-like receptors (iKIR: 2DL1, 2DL23, 3DL1, 3DL2), if they fail to engage a corresponding class I HLA ligand on recipient leukemia cells (missing ligand (ML) paradigm). We hypothesized that M-containing B-leaders (either MM or MT genotype), and potentially its association with KIR ML, may inform relapse and survival after HIDT using post-transplant cyclophosphamide (PTCy). A total of 322 patients with acute leukemia, MDS, lymphoma, CLL or CML, receiving a HIDT-PTCy from a single institution were evaluated with a median follow-up time of 45 months [range 6, 184]. Baseline characteristics included a median age of 50 years [19, 80], 47% non-white, HCT-CI ≥3 in 50%, PBSC graft in 80%, and myeloablative conditioning in 49%. M-containing B-leader genotype (either MM or MT) was seen in 42% and 44% of recipients and donors, respectively. The B-leader on the unshared donor-recipient haplotypes was matched (either T or M) in 61% of transplants. ML for iKIR 2DL1, 2DL23, 3DL1, and 3DL2 was noted in 29%, 20%, 24% and 72% respectively. Total ML was 0, 1, 2 and 3 in 10%, 43%, 40% and 7% respectively. In univariate analysis, an M-containing recipient B-leader genotype [R(M+)] improved OS and DFS compared to a recipient TT genotype [R(M-)] (75 vs. 53%, p<0.001; 66 vs. 47%, p<0.001), which was primarily due to a lower risk of relapse/progression (24% vs. 38%, p=0.012). In regard to total iKIR ML, the presence of 2-3 ML was associated with better overall (OS) and disease-free (DFS) survival compared with 0-1 (67% vs. 57%, p=0.08; 62% vs. 48%, p=0.019), which was due to lower relapse/progression (25% vs. 38%, p=0.015). There was no association of either recipient B-leader or total iKIR ML with the incidence of NRM, acute or chronic GVHD. When recipient B-leader and ML were combined, the detrimental effect of a R(M-) genotype was seen exclusively in patients with ML 0-1 (see figure). DFS for R(M-)/ML(0-1), R(M+)/ML(0-1), R(M-)/ML(2-3), R(M+)/ML(2-3) was 36%, 68%, 65% and 60%, respectively (p<0.001). Corresponding relapse/progression rates were 49%, 22%, 26% and 25%, respectively (P<0.001). In multivariate analysis, controlling for patient age/sex/race, disease risk index, donor age, HLA-DR mm, HLA-DP npmm and year of transplantation, both recipient B leader and total iKIR ML were independently associated with DFS (HR 0.57, p=0.002 and HR 0.67, p=0.026) and relapse/progression (HR 0.55, p=0.006 and HR 0.55, p=0.007). In summary, a recipient M-containing B-leader genotype (MM or MT) reduces relapse and improves survival following HIDT-PTCy, presumably through HLA-E-mediated effector cell engagement. Furthermore, the negative consequences of low total ML for iKIR, in terms of increased relapse risk and lower DFS, can be mitigated when a R(M+) B-leader is present. In addition to the clinical importance of this novel finding for optimizing HIDT-PTCy, it further supports the role of alloreactive donor NK cells for optimal GVL in this context. Figure 1 Figure 1. Disclosures Solh: Partner Therapeutics: Research Funding; Jazz Pharmaceuticals: Consultancy; ADCT Therapeutics: Consultancy, Research Funding; BMS: Consultancy.
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Stadnicka, A., Z. J. Bosnjak, J. P. Kampine, and W. M. Kwok. "Effects of sevoflurane on inward rectifier K+ current in guinea pig ventricular cardiomyocytes." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 1 (July 1, 1997): H324—H332. http://dx.doi.org/10.1152/ajpheart.1997.273.1.h324.
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The effects of sevoflurane on the inward rectifier potassium current (IKIR) were examined in guinea pig ventricular cardiomyocytes using the whole cell patch-clamp methodology. Sevoflurane had a unique dual effect on the steady-state current amplitude, producing a reversible, concentration- and voltage-dependent block of the inward current at potentials negative to the potassium equilibrium potential (EK) but enhancing the outward current positive to EK. Accordingly, the steady-state conductance negative to EK was reduced by sevoflurane, but conductance positive to EK was increased. The chord conductance-voltage relationship showed depolarizing shifts at 0.7, 1.3, and 1.6 mM sevoflurane. When the myocytes were dialyzed with 10 mM Mg2+, but not with 1.0 mM Mg2+, sevoflurane further slowed current activation kinetics. With 10 mM intracellular Mg2+, the outward current enhancement by sevoflurane and the associated shifts in half-activation potential were abolished. Polyamines abolished all effects of sevoflurane on IKIR. With the use of the Woodhull model for voltage-dependent block, we determined the sevoflurane interaction site with the inward rectifier potassium channel to be at an electrical distance of 0.2 from the extracellular side.
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Bastos-Oreiro, Mariana, Javier Anguita, Carolina Martínez-Laperche, Almudena Navarro, Lucía Fernandez, Pascual Balsalobre, Cristina Muñoz, et al. "Mismatches In Killer Immunoglobulin Receptor (KIR) Ligands and Inhibitory KIR Receptors Between Donor and Recipients Improve Survival After Non T Cell Depleted Haploidentical Transplantation." Blood 122, no. 21 (November 15, 2013): 2009. http://dx.doi.org/10.1182/blood.v122.21.2009.2009.
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Abstract Introduction Alloreactivity triggered by interaction of Killer immunoglobulin-like receptors (KIRs) on donor Natural killer (NK) cells and their ligands on recipients plays a role in the graft-versus-tumour effect. Different predictive models have been postulated for measuring alloreactivity: ligand incompatibility model, receptor-ligand model, missing ligand model and KIR gene-gene model. Our aim in this study is to evaluate the importance of differences in KIR and HLA genotype between donor and recipient (missing ligand model and KIR gene-gene model) in the setting of non T cell depleted haploidentical haematopoietic stem cell transplantation (HSCT) with high-dose, post-infusion cyclophosphamide (Cy) Patients and Methods 33 consecutive patients with haematological malignancies who received haploidentical HSCT with high-dose Cy post-transplantation between 2007 and 2013, and their donors were included for analysis (Table 1). HLA typing was used to identify KIR ligands HLA-B and HLA-C. KIR genotype was analyzed by PCR (KIR Typing, Miltenyi Biotec) on genomic DNA (Maxwell 16 Blood DNA Kit, Promega) from peripheral blood samples, and revealed with ethidium bromide after agarose gel electrophoresis. Results Demographic data and KIR genotype characteristics of donors and recipients are listed in Table 1. We found that KIR ligands mismatch between donor and recipient is related with improve of OS (52% vs. 82%; p=0,041) and DFS (63% vs. 22%; p=0,037) a year after transplant (Figure 1). Mismatch of inhibitors KIR receptors (iKIR) gene content between donors and recipients is also related with an improvement of OS (94% vs. 75%; p=0,049) and DFS (13% vs. 61%; p= 0,028) compared with no mismatch pairs. In the multivariable analysis, both KIR ligands mismatches (HR=4,38 CI:0.9-21; p=0,061) as well as iKIR mismatches (HR=4,15 CI:1-16; p=0,047), show a tendency to be independent variables for the reduction of disease relapse rate. Cumulative incidence of relapse for both variables studied is shown in Figure 2. Conspicuously, a sub-analysis in Hodgkin Lymphoma patients group shows and improve in DFS a year after transplant in patients with KIR ligands mismatches ( 100% vs. 48% p: 0,006) and iKIR mismatches (100% vs. % 33% p: 0,049), despite the small number of patients. Contrary to data published by other groups, patients receiving donor’s progenitors with Bx haplotype with centromeric genes (Cen-BB) did not show a benefit in survival (SG 85% vs. 90%, p= 0,05 and DFS 66% vs. 10%, p=0,047) a year after transplant Conclusion Our data suggest that in the setting of non T cell depleted haploidentical HSCT with high dose Cy post-infusion, KIR ligands and iKIR mismatch are related with an improve in survival, specially in the sub-group of patients with Hodgkin disease Disclosures: No relevant conflicts of interest to declare.
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Puwanant, Araya, and Robert L. Ruff. "INa and IKir are reduced in Type 1 hypokalemic and thyrotoxic periodic paralysis." Muscle & Nerve 42, no. 3 (June 29, 2010): 315–27. http://dx.doi.org/10.1002/mus.21693.
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Khomutov, Sergey Y. "International project INTERMAGNET and magnetic observatories of Russia: cooperation and progress." E3S Web of Conferences 62 (2018): 02008. http://dx.doi.org/10.1051/e3sconf/20186202008.
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Various aspects of international network of magnetic observatories INTERMAGNET such as standards, requirements for magnetic measurements, different status of published data, etc. are considered. Modern state of Russian segment of INTERMAGNET, its significance and contribution to global network are estimated. The features of monitoring of Earth’s magnetic field at observatories Paratunka (PET), Magadan (MGD), Khabarovsk (KHB) and Cape Schmidt (CPS) of IKIR FEB RAS and prospects are presented in detail.
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Tissone, Angela Isabel, Varinia Beatriz Vidal, Marcela Silvia Nadal, German Mato, and Yimy Amarillo. "Differential contribution of the subthreshold operating currents IT, Ih, and IKir to the resonance of thalamocortical neurons." Journal of Neurophysiology 126, no. 2 (August 1, 2021): 561–74. http://dx.doi.org/10.1152/jn.00147.2021.
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Our study expands the repertoire of ionic mechanisms known to be involved in the generation and control of resonance and provides the first experimental proof of previous theoretical predictions on resonance amplification mediated by regenerative hyperpolarizing currents. In thalamocortical neurons, we confirmed that the calcium current IT generates resonance, determined that the large steady conductance of the cationic current Ih curtails resonance, and demonstrated that the inward rectifier potassium current IKir amplifies resonance.
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Khomutov, Sergey Y. "Magnetic observations at Geophysical Observatory Paratunka IKIR FEB RAS: tasks, possibilities and future prospects." E3S Web of Conferences 20 (2017): 02002. http://dx.doi.org/10.1051/e3sconf/20172002002.
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С.Ю., Хомутов,. "Magnetic measurements at observatories of IKIR FEB RAS: from the present to the future." Вестник КРАУНЦ. Физико-математические науки, no. 4 (December 22, 2022): 209–24. http://dx.doi.org/10.26117/2079-6641-2022-41-4-209-224.
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Представлен краткий экскурс в историю магнитных измерений на обсервато- риях ИКИР ДВО РАН, которая начинается с Международного геофизического года (1957-1958 гг.) и последующих решений Правительства СССР и Президи- ума АН СССР, принятых в 1960-1962 гг. Рассмотрены достижения: (1) успешное ведение мониторинга магнитного поля по стандартам IAGA (регистрация вариаций на фотоленту, абсолютные наблюдения, подготовка часовых значе- ний полного вектора поля — H,D,Z); (2) переход в начале 2000-х с аналоговой аппаратуры на цифровую, завершившуюся сертификацией трёх обсерваторий ИКИР ДВО РАН (<Магадан>, <Паратунка> и <Хабаровск>) международной сетью INTERMAGNET (вариационные измерения с частотой 1 Гц, абсолютные наблюдения в ручном режиме, подготовка минутных значений полного вектора поля); (3) переобработка архивов аналоговых магнитограмм и цифро- вых данных, имеющихся с начала 1990-х. Сделан анализ имеющихся проблем (кадровых, финансовых, техногенной нагрузки, необходимости модернизации инфраструктуры и аппаратуры). A brief excursion into the history of magnetic measurements at the observatories of the IKIR FEB RAS, which begins with the International Geophysical Year (1957-1958) and subsequent decisions of the Government of the USSR and the Presidium of the Academy of Sciences of the USSR, adopted in 1960-1962, is presented. Achievements are considered: (1) successful monitoring of the magnetic field according to IAGA standards (registration of variations on a photographic tape, absolute observations, preparation of hourly values of the total field intesity components H,D,Z); (2) the transition in the early 2000s from analog to digital equipment, which ended with the certification of three observatories Magadan, Paratunka and Khabarovsk by the international INTERMAGNET network (variation measurements with a frequency of 1 Hz, absolute observations in manual mode, preparation of minute values of the magnetic field components); (3) reprocessing of archives of analog magnetograms and digital data available since the early 1990s. The analysis of the existing problems (personnel, financial, technogenic load, the need to modernize infrastructure and equipment) is made.
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Tella, Abiola Opemipo. "Traditional Rain Control Practice Through Indigenous Knowledge System and Technology Among Ikire People of Osun State, Southwest Nigeria." International Journal of Social Science Research and Review 5, no. 9 (September 11, 2022): 155–65. http://dx.doi.org/10.47814/ijssrr.v5i9.451.
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This paper aims to trace the history of rain prevention, and examine for documentation, the rituals involved. Traditional rain control in this context is considered as a process involving the making and preventing of rain to modify atmospheric condition of a place using Indigenous Knowledge and Technology (IKT). Rain control ritual is an age-long indigenous knowledge and technology aimed at influencing weather condition. As part of a broadened African society, the art of preventing rainfall is a part of the heritage resources practised by the people of Ikire in Osun State. This ritualistic art which is put to use mainly during socio-cultural gatherings such as festivals, feasts, burials, weddings, and naming ceremonies is called òjòwíwó or òjòmímó in local parlance. The help of rain doctors is sought by people who want to carry out any of these activities during rainy seasons to avoid disruption. Ethnographic method was used to elicit information. Research findings traced the art of rain prevention to Orunmila a god in Yoruba mythology. The rituals involved the use of the details of IKT which is significant in the response of the people to the ever-changing climate
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Amarillo, Yimy, Edward Zagha, German Mato, Bernardo Rudy, and Marcela S. Nadal. "The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons." Journal of Neurophysiology 112, no. 2 (July 15, 2014): 393–410. http://dx.doi.org/10.1152/jn.00647.2013.
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The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing Ih (hyperpolarization-activated cationic current), IT (low-threshold calcium current), and INaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of IA (fast transient A-type potassium current) and IKir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between three amplifying variables (activation of IT, activation of INaP, and activation of IKir) and three recovering variables (inactivation of IT, activation of IA, and activation of Ih) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation.
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Japhet, Akintoye. "A Survey of Teachers’ Experience in Implementing Yoruba Medium of Instruction in the Lower Primary Schools of Ikire Nigeria." Journal of Language and Education 3, no. 4 (December 31, 2017): 6–15. http://dx.doi.org/10.17323/2411-7390-2017-3-4-6-15.
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The paper investigated the local implementation of the National Policy of Education (NPE) on the use of mother tongues or the languages of the immediate community. Using a case study approach of Yoruba medium of instruction in Ikire in the south-western part of Nigeria, data were collected from 50 teachers from both private and public schools. These respondents were selected on being able to satisfy the following conditions: first, they should be able to communicate in Yoruba; second, they should have adequate teaching experience; third, they should have good academic qualifications; and fourth, they should have been teaching, for more than a year, Elementary Science (the particular classroom subject the study examined being taught to the pupils). These conditions ensured the teachers engaged had cognate experience in teaching a science subject that can reveal the level of terminology development within Yoruba as an adequate medium of mother tongue instruction. The result affirmed the advantages of Yoruba medium of instruction over English; however, Yoruba was not exclusively used for the pupils contrary to the expectation in the mother tongue medium of instruction policy. Most of the teachers used in the study preferred to employ a bilingual mode of instruction combining Yoruba with English, claiming that English had better educational resources for the subject they were teaching. This paper, though, based on a local case study, can be used to estimate the expected limitation to be encountered while implementing mother tongue instruction in a similar linguistic domain.
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Fujii, Jinshi. "Yanagita Kunio and the Culture Film: Discovering Everydayness and Creating/Imagining a National Community, 1935–1945." Arts 9, no. 2 (April 26, 2020): 54. http://dx.doi.org/10.3390/arts9020054.
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In wartime Japan, folklore studies (minzokugaku) as an academic discipline emerged at the same time as the rise of the culture film (bunka eiga). Both helped mobilize peripheral areas and firmly created the image of a unitary nation. This paper focuses on Living by the Earth (Tsuchi ni ikiru, 1941), directed by Miki Shigeru, and its spinoff photo album titled People of the Snow Country (Yukiguni no minzoku, 1944). Miki filmed rural life and ordinary people in the Tohoku region under the strong influence of Yanagita Kunio, a founder of Japanese folklore studies, and published the photo album in collaboration with Yanagita. In this project, vanishing customs were paradoxically regarded as objects impossible to photograph. However, that paradox enhanced the value of the project and made it easier to construct an imagined national community through the discourse of folklore studies.
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Polozov, Yuryi, and Nadezhda Fetisova. "Estimation of ionosphere state in AURORA online data analysis system." E3S Web of Conferences 127 (2019): 01003. http://dx.doi.org/10.1051/e3sconf/201912701003.
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The paper presents the results of detection of ionospheric anomalies in online mode according to the ionosonde data at Paratunka station, Kamchatka peninsula (IKIR FEB RAS). The developed algorithms have been implemented in Aurora system for online geophysical data analysis (http://lsaoperanalysis.ikir.ru:9180/lsaoperanalysis.html). The algorithms allow us to detect sudden anomalous changes of varying intensity in the dynamics of ionospheric parameters, as well as to estimate their characteristics. The efficiency of the system and the possibility of its application in space weather forecast tasks have been shown on the examples of events occurred in 2019.
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Bastos-Oreiro, Mariana, Javier Anguita, Carolina Martínez-Laperche, Lucía Fernández, Elena Buces, Almudena Navarro, Cristina Pascual, et al. "Inhibitory killer cell immunoglobulin-like receptor (iKIR) mismatches improve survival after T-cell-repleted haploidentical transplantation." European Journal of Haematology 96, no. 5 (July 23, 2015): 483–91. http://dx.doi.org/10.1111/ejh.12616.
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Tanaka, Masashi. "The effect of participation in summer camp of Boy Scout on IKIRU CHIKARA (zest for living), leadership and self-esteem." International Journal of Human Culture Studies 2018, no. 28 (January 1, 2018): 428–34. http://dx.doi.org/10.9748/hcs.2018.428.
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Oyewale, Abayomi Tolulope, Taiwo Adekanmi Adesakin, Olaoluwa Oyedeji, Adedeji Idowu Aduwo, and Mufutau Kolawole Bakare. "Impact Assessment of Poultry Discharge on the Physico-Chemical and Microbiological Water Quality of Olosuru Stream in Ikire, Southwestern Nigeria." Journal of Water Resource and Protection 10, no. 11 (2018): 1061–82. http://dx.doi.org/10.4236/jwarp.2018.1011062.
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HARA, Megumi. "Idō wo ikiru: Firipin ijū josei to fukusū no mobiritī (Living in Motion: Filipino Migrant Women and their Multiple Mobilities)." Social Science Japan Journal 21, no. 2 (2018): 360–63. http://dx.doi.org/10.1093/ssjj/jyy007.
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Akinola, Bisola S., Musa O. Awoyemi, Olaniran J. Matthew, and Adebiyi S. Adebayo. "Geophysical and hydro-chemical investigation of contamination plume in a basement complex formation around Sunmoye dumpsite in Ikire, Southwestern Nigeria." Modeling Earth Systems and Environment 4, no. 2 (April 4, 2018): 753–64. http://dx.doi.org/10.1007/s40808-018-0455-8.
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Krieger, Elizabeth, Urmila Sivagnanaling, Katherine Webb, Dana Broadway, Catherine Roberts, John M. McCarty, Christina M. Wiedl, et al. "Hematopoietic Cell Transplantation Donor Selection Reimagined: KIR-KIR Ligand Interactions and a Formalized Donor Risk Index Effective at Predicting Survival." Blood 134, Supplement_1 (November 13, 2019): 4616. http://dx.doi.org/10.1182/blood-2019-129384.
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Background When selecting a human leukocyte antigen (HLA) matched unrelated donor (URD) for hematopoietic cell transplantation (HCT) it is generally accepted that donor age, sex, ABO blood group and viral serologic status should be considered. However, the inter-relationship among these variables is not well established and a consensus on how strongly to consider each variable has not been reached. Selection of the optimal donor gets more complicated as new donor recipient pair (DRP) selection parameters, including killer immunoglobulin-like receptors (KIR) haplotypes are included. In this study we seek to develop a logic-based method to reduce the inconsistencies in donor selection in the HLA matched HCT. Methods VCU IRB approval was obtained for a retrospective review of eligible subjects who were adults with known KIR genotyping receiving HLA-A, B, C & DRB1 allelically matched URD HCT for hematologic malignancy between 2014 and 2017. Donor recipient pairs were selected based on donor age, sex match, CMV sero-status match, and ABO compatibility when possible; KIR genotype was not considered in DRP selection. KIR-KIR ligand interactions were calculated for each DR pair and interaction unit values were ascribed as follows; -1, when the donor possessed an inhibitory KIR (iKIR) and the recipient the corresponding HLA; +1, when the donor possessed iKIR and recipient lacked corresponding HLA (mKIR score, missing ligand). A novel inhibitory-missing KIR (IM-KIR) score was calculated for each HLA matched DRP by summing the interaction values as in equation 1. IM KIR Score = |iKIR| + |mKIRL| ………. [1] Univariate and multivariate analysis using Cox regression methods were utilized to evaluate donor parameters associated with overall survival. Weights of each donor risk variable (age, sex, CMV & ABO match) contribution were ascribed and summed up to determine donor risk parameter. Donor risk parameters and reciprocal-IM-KIR were finally combined into a donor risk index. Receiver operating characteristic curve- area under the curve (ROC-AUC) analysis was utilized to compare indices. Results Ninety-eight DRP with known HLA & KIR genotyping were studied. Median follow up at the time of analysis was 583 days. A higher IM-KIR score describes a DRP with increased iKIR-KIR ligand interactions and missing KIR ligand interactions; which was associated with a favorable survival after HCT, HR of 0.44 (95%CI: 0.26 to 0.73; P=0.002). Further analyses were performed using a reciprocal of this score. Univariate analysis of overall survival for donor age, sex match, ABO compatibility and CMV status were all statistically insignificant (p>0.05). However, the donor risk parameter was predictive of mortality with a hazard ratio (HR) of 2.76 (95% CI: 1.22-6.18, p=0.014). Covariate analysis of the donor risk parameter and reciprocal IM-KIR score were both predictive of survival independent of each other with HR 2.41 (1.05-5.54, p=0.038) and 2.35 (1.18-4.70, p=0.016) respectively. Combining the two into a donor risk index was predictive of survival with a HR of 2.38 (1.44-3.92, p=0.001). ROC-AUC comparison of survival for IM-KIR score and donor risk parameter showed statistically significant AUCs of 0.63 and 0.67 respectively. Further, the combined donor risk index shows improved sensitivity and specificity over the donor risk parameter with AUCs of 0.72 and 0.67 respectively. Conclusions A novel KIR-HLA interaction score, the IM-KIR score independently predicts survival in HLA matched DRP, as does a formalized donor risk parameter which includes non-HLA donor characteristics. Moreover, the addition of IM-KIR score to the donor risk parameter enhanced the specificity and sensitivity of predicting survival in these patients. If validated in a larger exploration and validation cohort this method of donor selection may improve the donor selection process, decreasing variability in clinical outcomes and improve overall survival. Disclosures No relevant conflicts of interest to declare.
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TRUBOVITZ, SARAH, JOHAN RENAUDIE, DAVID LAZARUS, and PAULA NOBLE. "Late Neogene Lophophaenidae (Nassellaria, Radiolaria) from the eastern equatorial Pacific." Zootaxa 5160, no. 1 (July 4, 2022): 1–158. http://dx.doi.org/10.11646/zootaxa.5160.1.1.
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Lophophaenidae is a clade of polycystine radiolarians that was highly abundant and diverse in the Late Neogene–Recent eastern equatorial Pacific (EEP). Despite their importance in fossil plankton assemblages, lophophaenids have been neglected because of their generally small size, complex morphology, and weak taxonomic framework. These challenges have left many lophophaenid concepts poorly defined or lacking formal description. Here we address this with a review of 101 lophophaenid taxa observed in EEP Middle Miocene–Recent marine sediments. We discuss existing lophophaenid genera Amphiplecta Haeckel 1881, Arachnocorallium Haeckel 1887, Arachnocorys Haeckel 1860, Botryopera Haeckel 1887, Ceratocyrtis Bütschli 1882, Lithomelissa Ehrenberg 1847, Lophophaena Ehrenberg 1847, and Peromelissa Haeckel 1881, including full species lists. We describe Pelagomanes n. gen., 23 new species: Amphiplecta kikimorae n. sp., Arachnocorys jorogumoae n. sp., Botryopera amabie n. sp., Botryopera babayagae n. sp., Botryopera bolotniki n. sp., Ceratocyrtis? chimii n. sp., Ceratocyrtis vila n. sp., Lithomelissa alkonost n. sp., Lithomelissa babai n. sp., Lithomelissa dybbuki n. sp., Lithomelissa sirin n. sp., Lophophaena arie n. sp., Lophophaena casperi n. sp., Lophophaena domovoi n. sp., Lophophaena gozui n. sp., Lophophaena ikiryo n. sp., Lophophaena ikota n. sp., Lophophaena kaonashii n. sp., Lophophaena leshii n. sp., Lophophaena rusalkae n. sp., Lophophaena shishigae n. sp., Lophophaena ushionii n. sp., and Pelagomanes ibburi n. sp., and one new subspecies, Arachnocorys pentacantha wanii n. subsp. In addition, we document 35 taxa in open nomenclature, and revise generic assignments of 10 species. The names of 32 previously-described species are upheld, but with clarified synonymies, discussion, and illustrations. This work contributes a practical framework for identifying tropical Late Neogene–Recent lophophaenid taxa, and demonstrates their rich morphological diversity.
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Zhang, Jiao, Yau-Chi Chan, Jenny Chung-Yee Ho, Chung-Wah Siu, Qizhou Lian, and Hung-Fat Tse. "Regulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel." American Journal of Physiology-Cell Physiology 303, no. 2 (July 15, 2012): C115—C125. http://dx.doi.org/10.1152/ajpcell.00326.2011.
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The successful generation of a high yield of mesenchymal stem cells (MSCs) from human induced pluripotent stem cells (iPSCs) may represent an unlimited cell source with superior therapeutic benefits for tissue regeneration to bone marrow (BM)-derived MSCs. We investigated whether the differential expression of ion channels in iPSC-MSCs was responsible for their higher proliferation capacity than BM-MSCs. The expression of ion channels for K+, Na+, Ca2+, and Cl− was examined by RT-PCR. The electrophysiological properties of iPSC-MSCs and BM-MSCs were then compared by patch-clamp experiments to verify their functional roles. Significant mRNA expression of ion channel genes including KCa1.1, KCa3.1, KCNH1, Kir2.1, SCN9A, CACNA1C, and Clcn3 was observed in both human iPSC-MSCs and BM-MSCs, whereas Kir2.2 and Kir2.3 were only detected in human iPSC-MSCs. Five types of currents [big-conductance Ca2+-activated K+ current (BKCa), delayed rectifier K+ current ( IKDR), inwardly rectifying K+ current ( IKir), Ca2+-activated K+ current ( IKCa), and chloride current ( ICl)] were found in iPSC-MSCs (83%, 47%, 11%, 5%, and 4%, respectively) but only four of them (BKCa, IKDR, IKir, and IKCa) were identified in BM-MSCs (76%, 25%, 22%, and 11%, respectively). Cell proliferation was examined with MTT or bromodeoxyuridine assay, and doubling times were 2.66 and 3.72 days for iPSC-MSCs and BM-MSCs, respectively, showing a 1.4-fold discrepancy. Blockade of IKDR with short hairpin RNA or human ether-à-go-go 1 (hEAG1) channel blockers, 4-AP and astemizole, significantly reduced the rate of proliferation of human iPSC-MSCs. These treatments also decreased the rate of proliferation of human BM-MSCs albeit to a lesser extent. These findings demonstrate that the hEAG1 channel plays a crucial role in controlling the proliferation rate of human iPSC-MSCs and to a lesser extent in BM-MSCs.
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Senitzer, D., J. Y. Sun, L. Gaidulis, A. Oki, A. Dagis, J. Palmer, and S. J. Forman. "The Effect of Inhibitory Killer-Cell Ig-Like Receptor(iKIR) Matching in Allogeneic Hematopoietic Cell Transplantation(HCT)." Biology of Blood and Marrow Transplantation 15, no. 2 (February 2009): 18–19. http://dx.doi.org/10.1016/j.bbmt.2008.12.054.
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Krieger, Elizabeth, Rehan Qayyum, and Amir Ahmed Toor. "Increased Inhibitory KIR-Ligand Interactions Confer Relapse Protection Following HLA Matched Unrelated Donor HCT for AML." Blood 136, Supplement 1 (November 5, 2020): 47. http://dx.doi.org/10.1182/blood-2020-134614.
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Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated graft versus leukemia effect (GVL) after hematopoietic stem cell transplant (HCT) for AML. There is considerable heterogeneity in the KIR gene and KIRL content of individuals, making it difficult to estimate the full clinical impact of NK cell alloreactivity following HCT. Herein, we validate a mathematical model accounting for KIR-KIRL interactions identifying donors with optimal NK cell-mediated alloreactivity and GVL. This retrospective study was performed on de-identified donor and recipient demographic and clinical outcomes data provided by the Center for International Blood and Marrow Transplant Research (CIBMTR). Donor recipient pairs (DRP) who underwent unrelated donor (URD) HCT for early and intermediate AML were included. KIR-KIRL interaction values were assigned as follows; if an inhibitory KIR (iKIR) on the NK cell encounters a ligand on its target, this will give the NK cell an inhibitory signal and this is scored as a single interaction(Figure 1b), as is the case, if there is no ligand for an inhibitory KIR, i.e., missing KIRL (mKIRL) (Figure 1c). Finally, activating KIR (aKIR) interacting with its ligands is similarly scored(Figure 1a). The absolute values of the iKIR and mKIR scores were summed to calculate the composite inhibitory-missing ligand (IM)-KIR score (Figure 1d). The study cohort was comprised of 2365 donor-recipient pairs (DRP) who underwent URD HCT for early or intermediate AML. Mean age was 53 years; 85% of DRPs were high-resolution 8/8 HLA-matched for HLA-A, -B, -C, and -DRB1. All patients received T cell replete grafts; 42% (n=996) received in vivo T cell depletion, 937 (94%) with anti-thymocyte globulin (ATG); 86% received a graft of mobilized peripheral blood stem cells (PBSC), 59% received myeloablative conditioning. This cohort was primarily of Caucasian descent (89%). When adjusted for recipient age, donor age, CMV status, KPS, GVHD prophylaxis, cytogenetics, disease status, conditioning regimen, in vivo T cell depletion, graft source, and sex match, relapse risk was significantly reduced in donor-recipient pairs (DRP) with higher inhibitory KIR-KIRL interaction and missing KIRL (mKIR) scores, with HR=0.86 (P=0.01) & HR=0.84 (P=0.02) respectively. This effect was not observed with activating KIR-KIRL interactions. Chronic GVHD and TRM were not significantly affected by iKIR, mKIR or aKIR. Given the significant individual impact of iKIR and mKIR, the summed inhibitory-missing ligand (IM-KIR) score was next assessed, and when this score was 5 (as opposed to <5), the IM-KIR score was also associated with lower relapse risk, HR 0.8 (P=0.004) (Figure 2a). Acute and chronic graft vs. host disease (GVHD), survival, GRFS, and relapse-free survival were not significantly different, likely due to increased TRM among these patients, HR 1.32 (P=0.01). Interaction analysis indicated that amongst the HLA matched DRP, ATG recipients with IM-KIR=5, had a lower relapse rate compared to those with an IM-KIR<5, HR 0.61 (p=0.001) (Figure 2b), among the cohort who did not receive ATG there was no significant difference in relapse among IM-KIR=5 and IM-KIR<5; thus, the use of ATG significantly modified the effect of IM KIR score in an interaction analysis (p=0.049), suggesting higher NK cell magnitude of KIR-KIRL interaction may compensate for the general increase of relapse in those who receive in vivo T cell depletion. Nevertheless, TRM was also increased in these patients, HR 1.49 (p=0.034), likely abrogating survival advantage from a lower relapse risk. This large international study confirms that unrelated DRPs with greater magnitude of inhibitory KIR-KIRL interactions confer significant relapse protection after MUD HCT in standard-risk AML. This challenges the notion that KIR are irrelevant to donor selection. Future clinical trials evaluating donor selection for URD HCT should include this measure to evaluate its value prospectively in uniformly treated patient cohorts, with adequate GVHD and antiviral prophylaxis to mitigate TRM. Disclosures No relevant conflicts of interest to declare.
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Yoshikawa, Akimasa, Akiko Fujimoto, Akihiro Ikeda, Teiji Uozumi, and Shuji Abe. "Monitoring of Space and Earth electromagnetic environment by MAGDAS project: Collaboration with IKIR - Introduction to ICSWSE/MAGDAS project." E3S Web of Conferences 20 (2017): 01013. http://dx.doi.org/10.1051/e3sconf/20172001013.
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