ALMA observations of the long wavelength dust continuum are used to estimate the interstellar medium (ISM) masses in a sample of 708 galaxies at z = 0.3 to 4.5 in the COSMOS field. The galaxy sample ...has known far-infrared luminosities and, hence, star formation rates (SFRs) and stellar masses ( ) from the optical-infrared spectrum fitting. The galaxies sample SFRs from the main sequence (MS) to 50 times above the MS. The derived ISM masses are used to determine the dependence of gas mass on redshift, , and specific SFR (sSFR) relative to the MS. The ISM masses increase approximately with the 0.63 power of the rate of increase in SFRs with redshift and the 0.32 power of the sSFR/sSFRMS. The SF efficiencies also increase as the 0.36 power of the SFR redshift evolution and the 0.7 power of the elevation above the MS; thus the increased activities at early epochs are driven by both increased ISM masses and SF efficiency. Using the derived ISM mass function, we estimate the accretion rates of gas required to maintain continuity of the MS evolution ( yr−1 at z > 2.5). Simple power-law dependencies are similarly derived for the gas accretion rates. We argue that the overall evolution of galaxies is driven by the rates of gas accretion. The cosmic evolution of total ISM mass is estimated and linked to the evolution of SF and active galactic nucleus activity at early epochs.
Photoredox catalysis has experienced a revitalized interest from the synthesis community during the past decade. For example, photoredox/Ni dual catalysis protocols have been developed to overcome ...several inherent limitations of palladium-catalyzed cross-couplings by invoking a single-electron transmetalation pathway. This Perspective highlights advances made by our laboratory since the inception of the photoredox/Ni cross-coupling of benzyltrifluoroborates with aryl bromides. In addition to broadening the scope of trifluoroborate coupling partners, research using readily oxidized hypervalent silicates as radical precursors that demonstrate functional group compatibility is highlighted. The pursuit of electrophilic coupling partners beyond (hetero)aryl bromides has also led to the incorporation of several new classes of C(sp2)-hybridized substrates into light-mediated cross-coupling. Advances to expand the radical toolbox by utilizing feedstock chemicals (e.g., aldehydes) to access radicals that were previously inaccessible from trifluoroborates and silicates are also emphasized. Additionally, several organic photocatalysts have been investigated as replacements for their expensive iridium- and ruthenium-based counterparts. Lastly, the net C–H functionalization of the radical partner in an effort to improve atom economy is presented. An underlying theme in all of these studies is the value of generating radicals in a catalytic manner, rather than stoichiometrically.
Under oxidative conditions, 1,4-dihydropyridines (DHPs) undergo a homolytic cleavage, forming exclusively a Csp3 -centered radical that can engage in the C–H alkylation of heterocyclic bases and ...1,4-quinones. DHPs are readily prepared from aldehydes, and considering that aldehydes normally require harsh reaction conditions to take part in such transformations, with mixtures of alkylated and acylated products often being obtained, this net decarbonylative alkylation approach becomes particularly useful. The present method takes place under mild reaction conditions and requires only persulfate as a stoichiometric oxidant, making the procedure suitable for the late-stage C–H alkylation of complex molecules. Notably, structurally complex pharmaceutical agents could be functionalized or prepared with this protocol, such as the antimalarial Atovaquone and antitheilerial Parvaquone, thus evidencing its applicability. Mechanistic studies revealed a likely radical chain process via the formation of a dearomatized intermediate, providing a deeper understanding of the factors governing the reactivity of these radical forebears.
The incorporation of C‐glycosides in drug design has become a routine practice for medicinal chemists. These naturally occurring building blocks exhibit attractive pharmaceutical profiles, and have ...become an important target of synthetic efforts in recent decades. Described herein is a practical, scalable, and versatile route for the synthesis of non‐anomeric and unexploited C‐acyl glycosides through a Ni/photoredox dual catalytic system. By utilizing an organic photocatalyst, a range of glycosyl‐based radicals are generated and efficiently coupled with highly functionalized carboxylic acids at room temperature. Distinctive features of this transformation include its mild conditions, impressive compatibility with a wide array of functional groups, and most significantly, preservation of the anomeric carbon: a handle for further, late‐stage derivatization.
Leading light: A practical and versatile route toward C‐acyl glycosides through Ni/Photoredox dual catalysis was developed. Key to this transformation is preservation of the anomeric carbon atom as a handle for further derivatization. An organic photocatalyst is utilized to generate an array of glycosyl‐based radicals that engage in cross‐coupling with in situ activated carboxylic acids. This process is operationally simple and shows broad functional‐group tolerance.
The development of synthetic tools to introduce saccharide derivatives into functionally complex molecules is of great interest, particularly in the field of drug discovery. Herein, we report a new ...route toward highly functionalized, arylated saccharides, which involves nickel‐catalyzed cross‐coupling of photoredox‐generated saccharyl radicals with a range of aryl‐ and heteroaryl bromides, triggered by an organic photocatalyst. In contrast to existing methods, the mild reaction conditions achieve arylation of saccharide motifs while leaving the anomeric carbon available, thus providing access to a class of arylated glycosides that has been underexplored until now. To demonstrate the potential of this strategy in late‐stage functionalization, a variety of structurally complex molecules incorporating saccharide moieties were synthesized.
Running mild: A new route toward highly functionalized, arylated saccharides through nickel‐catalyzed cross‐coupling of photoredox‐generated saccharyl radicals with a range of aryl‐ and heteroaryl bromides, triggered by an organic photocatalyst, was developed. In contrast to existing methods, the mild reaction conditions achieve arylation of saccharide motifs while leaving the anomeric carbon atom available, thereby providing access to underexplored arylated glycosides.
Heteroarylation via C–H functionalization has been synthetically challenging, but such transformations represent an atom-economical and highly convergent route toward complex molecules. Reported ...herein is a photoredox-catalyzed coupling between 2-trifluoroborato-4-chromanones and various heteroarenes through a Minisci pathway. Mesitylacridinium perchlorate, an organic photocatalyst, proved to be a better photocatalyst than transition-metal counterparts for such transformations. To highlight the utility of this approach, a library of unprecedented heteroaryl-substituted chromanones was generated that was composed of numerous, specifically substituted molecules containing a broad range of functional groups.
Vascularization of human brain organoids Matsui, Takeshi K; Tsuru, Yuichiro; Hasegawa, Koichi ...
Stem cells (Dayton, Ohio),
August 2021, Letnik:
39, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Human brain organoids are three-dimensional tissues that are generated in vitro from pluripotent stem cells and recapitulate the early development of the human brain. Brain organoids consist mainly ...of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes, and oligodendrocytes. However, all human brain organoids lack vasculature, which plays indispensable roles not only in brain homeostasis but also in brain development. In addition to the delivery of oxygen and nutrition, accumulating evidence suggests that the vascular system of the brain regulates neural differentiation, migration, and circuit formation during development. Therefore, vascularization of human brain organoids is of great importance. Current trials to vascularize various organoids include the adjustment of cultivation protocols, the introduction of microfluidic devices, and the transplantation of organoids into immunodeficient mice. In this review, we summarize the efforts to accomplish vascularization and perfusion of brain organoids, and we discuss these attempts from a forward-looking perspective.
A regioselective, nickel‐catalyzed photoredox allylation of secondary, benzyl, and α‐alkoxy radical precursors is disclosed. Through this manifold, a variety of linear allylic alcohols and allylated ...monosaccharides are accessible in high yields under mild reaction conditions. Quantum mechanical calculations DFT and DLPNO‐CCSD(T) support the mechanistic hypothesis of a Ni0 to NiII oxidative addition pathway followed by radical addition and inner‐sphere allylation.
Coming to light: Report herein is a highly regioselective, intermolecular, nickel‐catalyzed photoredox allylic substitution that expands both the radical and electrophile scope of dual photoredox/Ni‐catalyzed reactions. Quantum mechanical calculations shed light on the mechanistic pathway, supporting a Ni0 to NiII oxidative addition followed by an inner‐sphere radical addition. PC=photocatalyst, RP=radical precursor.
During neural development, the actin filament network must be precisely regulated to form elaborate neurite structures. N-WASP tightly controls actin polymerization dynamics by activating an actin ...nucleator Arp2/3. However, the importance of N-WASP-Arp2/3 signaling in the assembly of neurite architecture in vivo has not been clarified. Here, we demonstrate that N-WASP-Arp2/3 signaling plays a crucial role in the maturation of cerebellar Purkinje cell (PC) dendrites in vivo in mice. N-WASP was expressed and activated in developing PCs. Inhibition of Arp2/3 and N-WASP from the beginning of dendrite formation severely disrupted the establishment of a single stem dendrite, which is a characteristic basic structure of PC dendrites. Inhibition of Arp2/3 after stem dendrite formation resulted in hypoplasia of the PC dendritic tree. Cdc42, an upstream activator of N-WASP, is required for N-WASP-Arp2/3 signaling-mediated PC dendrite maturation. In addition, overactivation of N-WASP is also detrimental to dendrite formation in PCs. These findings reveal that proper activation of N-WASP-Arp2/3 signaling is crucial for multiple steps of PC dendrite maturation in vivo.
We present new observations of Fornax A taken at ∼1 GHz with the MeerKAT telescope and at ∼6 GHz with the Sardinia Radio Telescope (SRT). The sensitive (noise ∼16
μ
Jy beam
−1
), high-resolution ...(≲10″) MeerKAT images show that the lobes of Fornax A have a double-shell morphology, where dense filaments are embedded in a diffuse and extended cocoon. We study the spectral properties of these components by combining the MeerKAT and SRT observations with archival data between 84 MHz and 217 GHz. For the first time, we show that multiple episodes of nuclear activity must have formed the extended radio lobes. The modelling of the radio spectrum suggests that the last episode of injection of relativistic particles into the lobes started ∼24 Myr ago and stopped 12 Myr ago. More recently (∼3 Myr ago), a less powerful and short (≲1 Myr) phase of nuclear activity generated the central jets. Currently, the core may be in a new active phase. It appears that Fornax A is rapidly flickering. The dense environment around Fornax A has lead to a complex recent merger history for this galaxy, including mergers spanning a range of gas contents and mass ratios, as shown by the analysis of the galaxy’s stellar- and cold-gas phases. This complex recent history may be the cause of the rapid, recurrent nuclear activity of Fornax A.
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