Abstract
Establishment of spermatogonia throughout the fetal and postnatal period is essential for production of spermatozoa and male fertility. Here, we establish a protocol for in vitro ...reconstitution of human prospermatogonial specification whereby human primordial germ cell (PGC)-like cells differentiated from human induced pluripotent stem cells are further induced into M-prospermatogonia-like cells and T1 prospermatogonia-like cells (T1LCs) using long-term cultured xenogeneic reconstituted testes. Single cell RNA-sequencing is used to delineate the lineage trajectory leading to T1LCs, which closely resemble human T1-prospermatogonia in vivo and exhibit gene expression related to spermatogenesis and diminished proliferation, a hallmark of quiescent T1 prospermatogonia. Notably, this system enables us to visualize the dynamic and stage-specific regulation of transposable elements during human prospermatogonial specification. Together, our findings pave the way for understanding and reconstructing human male germline development in vitro.
S486P substitution, emerged and is rapidly spreading in the USA (appendix pp 6–7), and is the latest variant of concern.7 Although the features of XBB.1.5 were reported by Yue and colleagues,8 a ...comprehensive understanding of the virological characteristics of newly emerging variants is needed for sustained global health. ...neutralisation assay revealed that XBB.1.5 was robustly resistant to BA.2 breakthrough infection sera (41-fold versus B.1·1, 20-fold versus BA.2) and BA.5 breakthrough infection sera (32-fold versus B.1·1, 9·5-fold versus BA.5; appendix pp 6–7). Supported in part by AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers UTOPIA (JP223fa627001, to KS), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium and Kei Sato; JP21fk0108425, to Kei Sato; JP21fk0108432, to Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410039, to Kei Sato); JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (20K15767, Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); The Tokyo Biochemical Research Foundation (to Kei Sato); and the project of National Institute of Virology and Bacteriology, Programme EXCELES, funded by the European Union, Next Generation EU (LX22NPO5103, to Jiri Zahradnik).
Further increase in energy density of lithium batteries is needed for zero emission vehicles. However, energy density is restricted by unavoidable theoretical limits for positive electrodes used in ...commercial applications. One possibility towards energy densities exceeding these limits is to utilize anion (oxide ion) redox, instead of classical transition metal redox. Nevertheless, origin of activation of the oxide ion and its stabilization mechanism are not fully understood. Here we demonstrate that the suppression of formation of superoxide-like species on lithium extraction results in reversible redox for oxide ions, which is stabilized by the presence of relatively less covalent character of Mn
with oxide ions without the sacrifice of electronic conductivity. On the basis of these findings, we report an electrode material, whose metallic constituents consist only of 3d transition metal elements. The material delivers a reversible capacity of 300 mAh g
based on solid-state redox reaction of oxide ions.
Southern India occupies a central position in the Late Neoproterozoic–Cambrian Gondwana supercontinent assembly. The Proterozoic mosaic of southern India comprises a collage of crustal blocks ...dissected by Late Neoproterozoic–Cambrian crust-scale shear/suture zones. Among these, the Palghat–Cauvery Suture Zone (PCSZ) has been identified as the trace of the Cambrian suture representing Mozambique Ocean closure during the final phase of amalgamation of the Gondwana supercontinent. Here we propose a model involving Pacific-type orogeny to explain the Neoproterozoic evolution of southern India and its final amalgamation within the Gondwana assembly. Our model envisages an early rifting stage which gave birth to the Mozambique Ocean, followed by the initiation of southward subduction of the oceanic plate beneath a thick tectosphere-bearing Archean Dharwar Craton. Slices of the ocean floor carrying dunite–pyroxenite–gabbro sequence intruded by mafic dykes representing a probable ophiolite suite and invaded by plagiogranite are exposed at Manamedu along the southern part the PCSZ. Evidence for the southward subduction and subsequent northward extrusion are preserved in the PCSZ where the orogenic core carries high-pressure and ultrahigh-temperature metamorphic assemblages with ages corresponding to the Cambrian collisional orogeny. Typical eclogites facies rocks with garnet
+
omphacite
+
quartz and diagnostic ultrahigh-temperature assemblages with sapphirine
+
quartz, spinel
+
quartz and high alumina orthopyroxene
+
sillimanite
+
quartz indicate extreme metamorphism during the subduction–collision process. Eclogites and UHT granulites in the orogenic core define
P–
T maxima of 1000 °C and up to 20 kbar. The close association of eclogites with ultramafic rocks having abyssal signatures together with linear belts of iron formation and metachert in several localities within the PCSZ probably represents subduction–accretion setting. Fragments of the mantle wedge were brought up through extrusion tectonics within the orogenic core, which now occur as suprasubduction zone/arc assemblages including chromitites, highly depleted dunites, and pyroxene bearing ultramafic assemblages around Salem. Extensive CO
2 metasomatism of the ultramafic units generated magnesite deposits such as those around Salem. High temperature ocean floor hydrothermal alteration is also indicated by the occurrence of diopsidite dykes with calcite veining. Thermal metamorphism from the top resulted in the dehydration of the passive margin sediments trapped beneath the orogenic core, releasing copious hydrous fluids which moved upward and caused widespread hydration, as commonly preserved in the Barrovian amphibolite facies units in the PCSZ. The crustal flower structure mapped from PCSZ supports the extrusion model, and the large scale north verging thrusts towards the north of the orogenic core may represent a fold-thrust belt. Towards the south of the PCSZ is the Madurai Block where evidence for extensive magmatism occurs, represented by a number of granitic plutons and igneous charnockite massifs of possible tonalite–trondhjemite–granodiorite (TTG) setting, with ages ranging from ca. 750–560 Ma suggesting a long-lived Neoproterozoic magmatic arc within a >
200 km wide belt. All these magmatic units were subsequently metamorphosed, when the Pacific-type orogeny switched over to collision-type in the Cambrian during the final phase of assembly of the Gondwana supercontinent. One of the most notable aspects is the occurrence of arc magmatic rocks together with high
P/T rocks, representing the deeply eroded zone of subduction. The juxtaposition of these contrasting rock units may suggest the root of an evolved Andean-type margin, as in many arc environments the roots of the arc comprise ultramafic/mafic cumulates and the felsic rocks represent the core of the arc. The final phase of the orogeny witnessed the closure of an extensive ocean — the Mozambique Ocean — and the collisional assembly of continental fragments within the Gondwana supercontinent amalgam. The tectonic history of southern India represents a progressive sequence from Pacific-type to collision-type orogeny which finally gave rise to a Himalayan-type Cambrian orogen with characteristic magmatic, metasomatic and metamorphic factories operating in subduction–collision setting.
Circulating tumor DNA (ctDNA) carries information on tumor burden. However, the mutation spectrum is different among tumors. This study was designed to examine the utility of ctDNA for monitoring ...tumor burden based on an individual mutation profile.
DNA was extracted from a total of 176 samples, including pre- and post-operational plasma, primary tumors, and peripheral blood mononuclear cells (PBMC), from 44 individuals with colorectal tumor who underwent curative resection of colorectal tumors, as well as nine healthy individuals. Using a panel of 50 cancer-associated genes, tumor-unique mutations were identified by comparing the single nucleotide variants (SNVs) from tumors and PBMCs with an Ion PGM sequencer. A group of the tumor-unique mutations from individual tumors were designated as individual marker mutations (MMs) to trace tumor burden by ctDNA using droplet digital PCR (ddPCR). From these experiments, three major objectives were assessed: (a) Tumor-unique mutations; (b) mutation spectrum of a tumor; and (c) changes in allele frequency of the MMs in ctDNA after curative resection of the tumor.
A total of 128 gene point mutations were identified in 27 colorectal tumors. Twenty-six genes were mutated in at least 1 sample, while 14 genes were found to be mutated in only 1 sample, respectively. An average of 2.7 genes were mutated per tumor. Subsequently, 24 MMs were selected from SNVs for tumor burden monitoring. Among the MMs found by ddPCR with > 0.1% variant allele frequency in plasma DNA, 100% (8 out of 8) exhibited a decrease in post-operation ctDNA, whereas none of the 16 MMs found by ddPCR with < 0.1% variant allele frequency in plasma DNA showed a decrease.
This panel of 50 cancer-associated genes appeared to be sufficient to identify individual, tumor-unique, mutated ctDNA markers in cancer patients. The MMs showed the clinical utility in monitoring curatively-treated colorectal tumor burden if the allele frequency of MMs in plasma DNA is above 0.1%.
One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent ...interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis.
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•ORF3b proteins of SARS-CoV-2 and related animal viruses are IFN antagonists•SARS-CoV-2 ORF3b suppresses IFN more efficiently than its SARS-CoV ortholog•The anti-IFN activity of ORF3b depends on the length of its C terminus•An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases
COVID-19 pathogenesis is characterized by impaired IFN responses. Konno et al. identify ORF3b proteins of SARS-CoV-2 and related animal viruses as IFN antagonists. Their anti-IFN activity depends on the C-terminal length, and a natural ORF3b variant with increased IFN-suppressive activity was isolated from two severe COVID-19 cases.
Anthocyanins, sugars, and organic acids contribute to the appearance, health benefits, and taste of strawberries. However, their spatial distribution in the ripe fruit has been fully unrevealed. ...Therefore, we performed matrix-assisted laser desorption/ionization, MALDI-IMS, analysis to investigate their spatial distribution in ripe strawberries. The detection sensitivity was improved by using the TM-Sprayer for matrix application. In the receptacle, pelargonidins were distributed in the skin, cortical, and pith tissues, whereas cyanidins and delphinidins were slightly localized in the skin. In the achene, mainly cyanidins were localized in the outside of the skin. Citric acid was mainly distributed in the upper and bottom side of cortical tissue. Although hexose was distributed almost equally throughout the fruits, sucrose was mainly distributed in the upper side of cortical and pith tissues. These results suggest that using the TM-Sprayer in MALDI-IMS was useful for microscopic distribution analysis of anthocyanins, sugars, and organic acids in strawberries.
Mechanism of Fenton Oxidation of Levoglucosan in Water Enami, Shinichi; Morino, Yu; Sato, Kei
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
04/2023, Letnik:
127, Številka:
13
Journal Article
Recenzirano
Levoglucosan (Levo) is a major saccharide formed by the combustion of cellulosic materials. Levo was once considered an inert tracer of biomass-burning aerosols; however, recent studies have ...indicated that Levo in atmospheric condensed phases does indeed react with atmospheric reactants. Here, we report the results of a time-resolved mass spectrometric study of the oxidation of Levo in aqueous solutions with ferrous ion (Fe2+)/hydrogen peroxide (H2O2) (i.e., Fenton’s reagent). The major products of the Fenton oxidation of Levo were oxygen-atom-incorporated species (Levo+nO, n = 1–3). Experiments using Levo-d7 (all C–H bonds replaced by C–D) and D2O or H2 18O as the solvent revealed that OH predominantly (∼85% of all C–H bonds) abstracts H atoms attached to the carbon atoms possessing a hydroxyl moiety (−OH), which is followed by the formation of a carbonyl moiety (−CO). Subsequent hydration of these products results in the formation of geminal diols (detected as Levo+1O species). Our results also suggest the formation of α-hydroxy-hydroperoxides (detected as Levo+2O species) that exist in equilibrium, with the compounds possessing a −CO moiety and with H2O2. H-abstractions from −O-H were found to be a minor reaction pathway (≤5% of all H-abstractions). The present proposed oxidation mechanisms improve our understanding of how the chemical components of atmospheric condensed phases change by metal-catalyzed aging processes without sunlight.
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