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Biology subjects

Han, Y.

Publications and source records attributed to Han, Y..

22 records · Page 2Linked to original sources

Leukocyte counts based on site-specific DNA methylation analysis

The composition of white blood cells is usually assessed by histomorphological parameters or flow cytometric measurements. Alternatively, leukocyte differential counts (LDCs) can be estimated by deconvolution algorithms for genome-wide DNA methylation (DNAm) profiles. We identified cell-type specific CG dinucleotides (CpGs) that facilitate relative quantification of leukocyte subsets. Site-specific analysis of DNAm levels by pyrosequencing provides similar precision of LDCs as conventional methods, whereas it is also applicable to frozen samples and requires only very small volumes of blood. Furthermore, we describe a new approach for absolute quantification of cell numbers based on a non-methylated reference DNA. Our \"Epi-Blood-Count\" facilitates robust and cost effective analysis of blood counts for clinical application.

molecular biology

A single-cell anatomical blueprint for intracortical information transfer from primary visual cortex

The wiring diagram of the neocortex determines how information is processed across dozens of cortical areas. Each area communicates with multiple others via extensive long-range axonal projections 1-6, but the logic of inter-area information transfer is unresolved. Specifically, the extent to which individual neurons send dedicated projections to single cortical targets or distribute their signals across multiple areas remains unclear5,7-20. Distinguishing between these possibilities has been challenging because axonal projections of only a few individual neurons have been reconstructed. Here we map the projection patterns of axonal arbors from 591 individual neurons in mouse primary visual cortex (V1) using two complementary methods: whole-brain fluorescence-based axonal tracing21,22 and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq)23. Although our results confirm the existence of dedicated projections to certain cortical areas, we find these are the exception, and that the majority of V1 neurons broadcast information to multiple cortical targets. Furthermore, broadcasting cells do not project to all targets randomly, but rather comprise subpopulations that either avoid or preferentially innervate specific subsets of cortical areas. Our data argue against a model of dedicated lines of intracortical information transfer via \"one neuron - one target area\" mapping. Instead, long-range communication between a sensory cortical area and its targets may be based on a principle whereby individual neurons copy information to, and potentially coordinate activity across, specific subsets of cortical areas.

neuroscience

Releasing potential power of terpene synthases by a robust precursor supply platform

Approximately 76,000 discovered makes terpenoids the largest family of natural products in nature with widespread applications. The wide-spectrum of structural diversity of the terpenoids were largely due to the variable skeletons generated by terpene synthases. The number of terpene skeletons found in nature, however, were so much more than those conceivably generated from known terpene synthases and the limited characterized terpene synthases also make no chance for some useful terpenoids overproduction in microbe. Here, we first demonstrated that the promiscuous synthases in vivo can produce more variable terpenoid products by converting precursors of different lengths (C10, C15, C20, C25). This discovery was prompted by the development of an efficient in vivo platform by combining the two promiscuous terpene synthases and three prenyltransferases to generate 50 terpenoids, at least 3 ring systems of which were completely new. Furthermore, protein engineering was further integrated to enhance product diversity. Clearly, the work is expected to dramatically reshape the terpenoid research by widening the flexibility of the terpene synthases for the fresh discovery or creation of the new terpenoid compounds by skeleton reframing.

biochemistry

The house spider genome reveals an ancient whole-genome duplication during arachnid evolution

The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum. We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs in P. tepidariorum suggests that many have been subject to neofunctionalization and/or subfunctionalization since their duplication, and therefore may have contributed to the diversification of spiders and other pulmonate arachnids.

genomics