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By using Pd0 /Mandyphos, we achieved a three-component aminoarylation of alkynes to generate enamines, which are then hydrolyzed to either α-arylphenones or α,α-diarylketones. This Pd-catalyzed method overcomes established known pathways to enable the use of amines as traceless directing groups for C-C bond formation.

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos.sup.1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis. Adult human tissues from diverse sites around the body are used to reconstruct cellular phylogenies from early development, using somatic mutations as an internal barcode., Author(s): Seongyeol Park [sup.1] [sup.2] , Nanda Maya Mali [sup.3] , Ryul Kim [sup.1] , Jeong-Woo Choi [sup.3] [sup.4] , Junehawk Lee [sup.5] , Joonoh Lim [sup.1] , Jung Min [...]

Spectroscopic multiplex bioassay allows the rapid and simultaneous detection of various biomarkers in biomedical applications. The high cost and bulky configuration of conventional spectrometers hinder the decentralization of biomedical instruments for point‐of‐care diagnostics. Here a flat‐field lens grating‐based microspectrometer (FLG‐µSPEC) is reported for continuous detection of multi‐target nucleic acid amplification. FLG‐µSPEC features the vertical integration of microslit, integrated flat‐field lens and transmission grating (FLG), concave mirror, and CMOS line sensor. FLG effectively corrects the field curvature by flattening the focal plane of dispersed wavelengths and also facilitates compact module packaging. FLG‐µSPEC module is precisely assembled into a dimension of 10 mm × 16 mm × 10 mm. The average spectral resolution exhibits 3.4 ± 0.9 nm over an operating range of 500 to 950 nm. A spectral detection system utilizing FLG‐µSPEC demonstrates the amplification of lambda DNA (휆‐DNA) for each target, exhibiting a high correlation with the obtained result from a conventional real‐time PCR (qPCR) machine. Furthermore, multiplex qPCR analysis using FLG‐µSPEC and spectral deconvolution successfully demonstrates simultaneous and accurate quantification of three different targets. The FLG‐µSPEC module offers diverse on‐demand analytical applications, including not only multiplex bioassay but also environmental monitoring. [ABSTRACT FROM AUTHOR]

We report a Rh-catalyzed enantioselective cycloisomerization of α,ω-heptadienes to afford cyclohexenes bearing quaternary carbon centers. Rhodium(I) and a new SDP ligand promote chemoselective formation of a cyclohex-3-enecarbaldehyde motif that is inaccessible by the Diels-Alder cycloaddition. Various α,α-bisallylaldehydes rearrange to generate six-membered rings by a mechanism triggered by aldehyde C-H bond activation. Mechanistic studies suggest a pathway involving regioselective carbometalation and endocyclic β-hydride elimination.

We describe a Rh-catalyzed desymmetrization of all-carbon quaternary centers from α,α-bis(allyl)aldehydes by a cascade featuring isomerization and hydroacylation. This desymmetrization competes with two other novel olefin functionalizations that are triggered by C-H bond activation, including carboacylation and bisacylation. A BIPHEP ligand promotes enantioselective formation of α-vinylcyclopentanones. Mechanistic studies support irreversible and enantioselective olefin-isomerization followed by olefin-hydroacylation.

The dehydroformylation of aldehydes to generate olefins occurs during the biosynthesis of various sterols, including cholesterol in humans. Here, we implement a synthetic version that features the transfer of a formyl group and hydride from an aldehyde substrate to a strained olefin acceptor. A Rhodium (Xantphos)(benzoate) catalyst activates aldehyde carbon-hydrogen (C-H) bonds with high chemoselectivity to trigger carbon-carbon (C-C) bond cleavage and generate olefins at low loadings (0.3 to 2 mole percent) and temperatures (22° to 80°C). This mild protocol can be applied to various natural products and was used to achieve a three-step synthesis of (+)-yohimbenone. A study of the mechanism reveals that the benzoate counterion acts as a proton shuttle to enable transfer hydroformylation.

Porphyry Cu, and porphyry Cu–Au deposits, are associated with arc magmatism and their ore-forming systems generally follow the magmatic evolution of typical arcs. However, most arc magmas are barren and giant economic porphyry Cu ± Au deposits are rare. In this study, we model variations in rare earth element concentrations in evolving arc magmas and giant porphyry Cu ± Au systems to quantify the percentage of the fractionating minerals required to produce the observed changes. We find that, during the andesitic stage of fractionation, ore-forming systems in thick crusts fractionate ~35% more amphibole than an average of thick arc magma systems (the thick-crust reference suite) and that ore-forming systems in thin crusts fractionate twice as much amphibole as their equivalent thin-arc magma reference suite. Thick-crust ore-forming suites also fractionate ~50% less plagioclase, and thin-crust ore systems ~40% less plagioclase, than their associated reference suites during the same andesitic stage of fractionation. Taken together, these observations imply that ore-producing magmas are appreciably wetter than their associated barren reference suites. Our modeling also shows that ~80% more amphibole is required to reproduce the andesite stage of fractionation in the thick-crust reference suite than in its thin-crust equivalent, suggesting that magmas produced under thick crusts are wetter than those produced under thin crusts. On the other hand, the chalcophile element contents of the thick- and thin-crust ore-forming systems are similar to and higher than those of the thick- and thin-crust reference suites, respectively. Therefore, we suggest that the high water content plays a critical role in the formation of giant porphyry Cu ore in thick crusts, whereas both high chalcophile contents and high water contents are required to form giant porphyry Cu–Au deposits in thin crusts. The high fraction of amphibole fractionation in giant economic porphyry suites, compared with their relevant reference suites, results in lower Y in the ore-associated suites and this difference increases with fractionation. As a consequence, plots of Y against MgO can be used to identify porphyries that have economic potential and are preferred to Sr/Y plots because they are less affected by the intense alteration associated with giant porphyry Cu ± Au deposits. [ABSTRACT FROM AUTHOR]

Aim: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. Methods: We analyzed WGS data of 634 ASD families and performed genome‐wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD‐associated STR loci. Results: In ASD cases, rare STR expansions predominantly occurred in early cortical layer‐specific genes involved in neurodevelopment, highlighting the cellular specificity of STR‐associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD‐associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non‐carriers. Conclusion: Short tandem repeat expansions in cortical layer‐specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under‐investigated population. [ABSTRACT FROM AUTHOR]

Catalytic hydroboration and hydrosilylation have emerged as promising strategies for the reduction of unsaturated hydrocarbons and carbonyl compounds, as well as for the dearomatization of N-heteroarenes. Various catalysts have been employed in these processes to achieve the formation of reduced products via distinct reaction pathways and intermediates. Among these intermediates, N-silyl enamines and N-boryl enamines, which are derived from hydrosilylation and hydroboration, are commonly underestimated in this reduction process. Because these versatile intermediates have recently been utilized in situ as nucleophilic reagents or dipolarophiles for the synthesis of diverse molecules, an expeditious review of the synthesis and utilization of N-silyl and N-boryl enamines is crucial. In this review, we comprehensively discuss a wide range of hydrosilylation and hydroboration catalysts used for the synthesis of N-silyl and N-boryl enamines. These catalysts include main-group metals (e.g., Mg and Zn), transition metals (e.g., Rh, Ru, and Ir), earth-abundant metals (e.g., Fe, Co, and Ni), and non-metal catalysts (including P, B, and organocatalysts). Furthermore, we highlight recent research efforts that have leveraged these versatile intermediates for the synthesis of intriguing molecules, offering insights into future directions for these invaluable building blocks. [ABSTRACT FROM AUTHOR]