Uniaxial strain effects on the superconducting transition in Re-doped Hg-1223 cuprate superconductors

The effects of uniaxial strain and hydrostatic pressure on Hg0.83Re0.18Ba2Ca2.4Cu3.6O14 [Hg0.83(Re0.18)-1223] were investigated by ac magnetic measurements under stress corresponding to a pressure of 20 GPa at maximum. According to a previous thermal study based on the Ehrenfest relation, in-plane contraction should increase the superconducting transition temperature Tc, whereas out-of-plane contraction should decrease Tc. This suggests that the increase in Tc under hydrostatic-pressure contraction must be smaller than that under in-plane contraction. However, the present uniaxial-strain experiments revealed enhancement of Tc under both in-plane and out-of-plane contraction, and the largest enhancement was observed under hydrostatic-pressure contraction. According to a band calculation, all contraction styles induce hole doping from the HgO blocks to the CuO2 blocks, and hydrostatic-pressure contraction yields the largest hole doping among three contractions. This behavior explains well a series of changes in Tc in the stress region of below 8 GPa. More specifically, under hydrostatic-pressure contraction, Tc exhibited an increase, a decrease, and another increase with increasing pressure, and this multistep change is similar to that observed in Bi-2223-type cuprate superconductors, suggesting that it is necessary to distinguish the effect of strain on the middle CuO2 plane in the three-CuO2-plane package from that on the outer planes

Hydrostatic pressure effects on superconducting transition of nanostructured niobium highly strained by high-pressure torsion

We study the effects of hydrostatic pressure (HP) compression on the superconducting transition of severely strained Nb samples, whose grain sizes are reduced to the submicrometer level. Engineered granularity by high-pressure torsion (HPT) treatment changes the strength of coupling between submicrometer-scale grains and introduces lattice strain. We attempt to utilize the initially accumulated shear strain in the starting material for increasing the superconducting transition temperature Tc under HP compression. The HP effects on non-strained Nb have already been investigated in the pressure regime over 100 GPa by Struzhkin et al. [Phys. Rev. Lett. 79, 4262 (1997)], and Tc reportedly exhibited an increase from 9.2 to 9.9 K at approximately 10 GPa. (1) Slightly strained Nb in the HPT treatment exhibits the increase in Tc under HP due to the strengthening of the intergrain coupling, so the pressure scale of the pressure response observed by Struzhkin et al. is reduced to approximately one-seventh at the maximum. (2) Prominently strained Nb in the HPT treatment exhibits the increase in Tc under HP due to a reduction in structural symmetry at the unit-cell level: In a Nb sample subjected to HPT (6 GPa, 10 revolutions), Tc exceeds 9.9 K at approximately 2 GPa. According to our first-principle calculations, the reduction in the structural symmetry affords an increase in the density of states at the Fermi energy, thereby yielding a prominent increase in Tc at low pressures

Recent Progress of Flower Colour Modification by Biotechnology

Genetically-modified, colour-altered varieties of the important cut-flower crop carnation have now been commercially available for nearly ten years. In this review we describe the manipulation of the anthocyanin biosynthesis pathway that has lead to the development of these varieties and how similar manipulations have been successfully applied to both pot plants and another cut-flower species, the rose. From this experience it is clear that down- and up-regulation of the flavonoid and anthocyanin pathway is both possible and predictable. The major commercial benefit of the application of this technology has so far been the development of novel flower colours through the development of transgenic varieties that produce, uniquely for the target species, anthocyanins derived from delphinidin. These anthocyanins are ubiquitous in nature, and occur in both ornamental plants and common food plants. Through the extensive regulatory approval processes that must occur for the commercialization of genetically modified organisms, we have accumulated considerable experimental and trial data to show the accumulation of delphinidin based anthocyanins in the transgenic plants poses no environmental or health risk

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Myeloblasts transition to megakaryoblastic immunophenotypes over time in some patients with myelodysplastic syndromes.

ObjectivesIn myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express a megakaryocyte-lineage molecule, CD41, and such patients show extremely poor prognosis. This is the first study to evaluate whether myeloblasts transition to CD41+ blasts over time and to investigate the detailed immunophenotypic features of CD41+ blasts in MDS.MethodsWe performed a retrospective cohort study, in which time-dependent changes in blast immunophenotypes were analyzed using multidimensional flow cytometry (MDF) in 74 patients with MDS and AML (which progressed from MDS).ResultsCD41+ blasts (at least 20% of CD34+ blasts expressing CD41) were detected in 12 patients. In five of these 12 patients, blasts were CD41+ from the first MDF analysis. In the other seven patients, myeloblasts (CD34+CD33+CD41- cells) transitioned to megakaryoblasts (CD34+CD41+ cells) over time, which was often accompanied by disease progression (including leukemic transformation). These CD41+ patients were more frequently observed among patients with monosomal and complex karyotypes. CD41+ blasts were negative for the erythroid antigen, CD235a, and positive for CD33 in all cases, but CD33 expression levels were lower in three cases when compared with CD34+CD41- blasts. Among the five CD41+ patients who underwent extensive immunophenotyping, CD41+ blasts all expressed CD61, but two cases had reduced CD42b expression, three had reduced/absent CD13 expression, and three also expressed CD7.ConclusionsMyeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients

Emergence of CD41+ blasts with time in sequential analyses.

The data from three cases (Cases 2, 3, and 5 in Table 3) are shown. Panels A and B in each case show data when CD34+ blasts (red dots) were negative for CD41. The panels C-F in each case are data when CD34+ blasts (red dots) became positive for CD41 with time (D). Other cell fractions (green and blue dots) were negative for CD41 (E and F). (DOCX)</p

A CD41 false-positive case analyzed by imaging FCM.

[Left panel] A cytospin slide prepared from the FCM sample showing that platelets adhered to various cells (arrows). [Middle panel] A: Singlet events were displayed on the FSC versus SSC plot, and cells with low SSC were gated. A P1 gate was used to identify platelets. B: Low SSC cells (gated in panel A) were displayed on the CD34 versus CD45 plot. CD34+ blasts (red dots) and CD45-bright cells were gated. C: CD45-bright cells in Panel B were displayed on SSC versus CD45 plots, and lymphocytes (blue dots) were gated. D: Events in P1 (Panel A) were displayed on SSC versus CD41 plots and platelets (CD41+ cells) were gated. E: CD34+ blasts were displayed on the CD41 versus CD33 plot. CD41+ blasts (BL41+) and CD41- blasts (BL41-) were gated. F: Lymphocytes were displayed on the CD41 versus CD33 plot. CD41+ lymphocytes (Ly41+) and CD41- lymphocytes (Ly41-) were gated. [Right panel] Images of various cell fractions gated in the middle panel. A: Platelets. B: CD41+ blasts. C: CD41- blasts. D: CD41+ lymphocytes. E: CD41- lymphocytes. The arrow head indicate RBC ghost, which is observed in every cell fraction. The arrows indicate platelets adhering to leukocytes, which caused false CD41-positivity in leukocytes. Platelet adherence was observed in CD41-positive cell fractions (B and D), but not in CD41-negative cell fractions (C and E). Note that because the imaging FCM captures cell images from one direction, platelet adherence to the back surface of leukocytes was not detected. (DOCX)</p

Characteristics of CD41+ patients.

ObjectivesIn myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express a megakaryocyte-lineage molecule, CD41, and such patients show extremely poor prognosis. This is the first study to evaluate whether myeloblasts transition to CD41+ blasts over time and to investigate the detailed immunophenotypic features of CD41+ blasts in MDS.MethodsWe performed a retrospective cohort study, in which time-dependent changes in blast immunophenotypes were analyzed using multidimensional flow cytometry (MDF) in 74 patients with MDS and AML (which progressed from MDS).ResultsCD41+ blasts (at least 20% of CD34+ blasts expressing CD41) were detected in 12 patients. In five of these 12 patients, blasts were CD41+ from the first MDF analysis. In the other seven patients, myeloblasts (CD34+CD33+CD41- cells) transitioned to megakaryoblasts (CD34+CD41+ cells) over time, which was often accompanied by disease progression (including leukemic transformation). These CD41+ patients were more frequently observed among patients with monosomal and complex karyotypes. CD41+ blasts were negative for the erythroid antigen, CD235a, and positive for CD33 in all cases, but CD33 expression levels were lower in three cases when compared with CD34+CD41- blasts. Among the five CD41+ patients who underwent extensive immunophenotyping, CD41+ blasts all expressed CD61, but two cases had reduced CD42b expression, three had reduced/absent CD13 expression, and three also expressed CD7.ConclusionsMyeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients.</div