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Difference in TMPRSS2 usage by Delta and Omicron variants of SARS-CoV-2 : Implication for a sudden increase among children
No full textIt has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs
キンユウ サービス テイキョウガイシャ ノ ヒエイリ カツドウ ホウジン ニ タイスル エイギョウ シエン ホウサク ： キンユウ キカン ノ ホウジン コキャク ト ノ コンタクト データ ニ モトズク シミュレーション ト シンライセイ モデル オ モチイタ エイギョウ ホウサク ノ カイセキ ケントウ
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シキュウセンキンショウ ノ シキュウ ナイマク ニオケル ケモカインリガンド 26 ノ ハツゲンゾウカ ト ジョウヒカンヨウテンカン エノ カンヨ
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コウチュウキュウ ト リンパキュウ ノ ヒリツ ワ ソウキ イガン ノ ソシキガタ オ ヨソク スル ノニ ユウヨウ ナ シヒョウ デ アル
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リンショウ オウヨウ ノ タメ ノ ゴクボソケイ ヒカリファイバ アツリョク センサ オ モチイタ ジンウ ナイアツ ジドウ セイギョ システム
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モロッコ ノ ダイキボ カンガイ チク ニ オケル ハイスイ カンリ ノ ホウカツテキ ヒョウカ ニ カンスル ケンキュウ
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Identification of histidine residues that affect the T/R-state conformations of human hemoglobin using constant pH molecular dynamics simulations
Get PDFPrevention of liver metastasis via the pharmacological suppression of AMIGO2 expression in tumor cells
No full textAMIGO2 adheres to liver endothelium and induces liver metastasis. We revealed that genetically altering AMIGO2 expression in tumor cells affects their liver metastatic potential, depending on the AMIGO2 expression level. The aim of this study was to prevent liver metastasis by pharmacologically suppressing AMIGO2 expression. For screening, we used the mouse LV12 cells because of their affinity to adhere to liver endothelium and metastasize the liver owing to elevated AMIGO2 expression. Of the 285 compounds tested, 17 reduced AMIGO2 mRNA expression. We subsequently screened for compounds that inhibited tumor cell adhesion to liver endothelium and identified five compounds that inhibit three signaling pathways (MEK, JAK, and JNK). Treatment with these compounds inhibited liver metastasis of LV12 cells. Next, we used clinically available signal inhibitors (MEK inhibitor trametinib, JAK inhibitor ruxolitinib, and JNK inhibitor SP600125), and found that ruxolitinib inhibits AMIGO2 expression more stably. Furthermore, ruxolitinib inhibited the adhesion of LV12 cells to liver endothelium and suppressed liver metastasis. Using the MKN45 gastric cancer cells, we confirmed that ruxolitinib could prevent liver metastasis of human cancer cells. These results demonstrate that pharmacological inhibition of AMIGO2 expression in tumor cells is a promising novel strategy to prevent and control liver metastasis
Three Patients of the Early Onset Epileptic Spasms without Hypsarrhythmia
No full textEpileptic spasms without hypsarrhythmia occur when patients do not display hypsarrhythmia on electroencephalogram (EEG) at the onset and throughout the clinical course. We report three patients of epileptic spasms in patients with early onset, all of whom experienced other types of seizures. We detail three patients (two boys and one girl) of epileptic spasms without hypsarrhythmia, occurring between 1 and 3 months of age, with no abnormalities detected on neurometabolic analysis and brain magnetic resonance imaging. Long-term video-EEG monitoring revealed epileptic spasms with focal onset seizures in two patients, and epileptic spasms followed by generalized tonic-clonic seizures in one patient. Hypsarrhythmia was never observed in repeated EEG examinations. Two patients achieved seizure freedom and improved development through treatment with topiramate alone or in combination with valproate, without requiring hormonal therapies or vigabatrin. The remaining patient achieved seizure freedom following administration of antiseizure medications, including topiramate, after a trial of adrenocorticotropic hormone therapy. We report the cases of three patients with early onset epileptic spasms without hypsarrhythmia. All patients achieved seizure freedom after topiramate treatment. Topiramate may be considered as a relatively effective antiseizure medication for early onset epileptic spasms without hypsarrhythmia
Flow stress curves for 980MPa- and 1.5GPa-class ultra-high-strength steel sheets weakened under high-stress triaxiality
Get PDFThe weakening behavior of ultra-high-strength steel(UHSS) remains unknown, even though it is a requirement for the accurate prediction of strain localization and ductile fracture in automobile applications. In this study, we, therefore, revealed the stress–strain curves of UHSSs up to their ductile fracture under different stress triaxialities for the first time. Smooth and notched tiny round-bar specimens cut from UHSSs with 1.6-mm thickness were subjected to tensile tests, during which the forces and neck diameters of the specimens were measured. Notably, the evaluated flow stresses in the 1.5 GPa-class notched UHSS specimens exhibited weakening of up to 3 %. This was in contrast to the 980 MPa-class UHSS specimens, which did not exhibit notch-induced weakening. The absence of weakening during stress measurements, as confirmed by synchrotron X-ray diffraction (XRD) analysis, suggested that weakening was caused by material damage. However, the weakening behavior did not follow the previously developed damage models based on microvoid formation. The volume fraction of the microvoids, as observed by X-ray computer tomography, was extremely small (at 0.2 %) and cannot account for the 3 % material weakening indicated by the flow stress measurement results. A new damage mechanism, associated with unobservable small lattice vacancies, was implied in UHSSs deformation under high stress triaxialities