Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

Developmental-stage-related patterns of gene expression correlate with codon usage and genomic GC content in stem cell hierarchies

Existence and Iteration of Positive Solutions for Multipoint Boundary Value Problems Dependence on the First Order Derivative with One-Dimensional p-Laplacian

Abstract In this paper, we study the existence of monotone positive solutions for the following nonlinear m-point singular boundary value problem with p-Laplacian operator. The main tool is the monotone iterative technique. We obtain not only the existence of positive solutions for the problem, but also establish iterative schemes for approximating solution. Mathematics Subject Classification: 34B1

Derivation and Characterization of Hepatic Progenitor Cells from Human Embryonic Stem Cells

The derivation of hepatic progenitor cells from human embryonic stem (hES) cells is of value both in the study of early human liver organogenesis and in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Here, we report for the first time the generation of hepatic progenitor cells derived from hES cells. Hepatic endoderm cells were generated by activating FGF and BMP pathways and were then purified by fluorescence activated cell sorting using a newly identified surface marker, N-cadherin. After co-culture with STO feeder cells, these purified hepatic endoderm cells yielded hepatic progenitor colonies, which possessed the proliferation potential to be cultured for an extended period of more than 100 days. With extensive expansion, they co-expressed the hepatic marker AFP and the biliary lineage marker KRT7 and maintained bipotential differentiation capacity. They were able to differentiate into hepatocyte-like cells, which expressed ALB and AAT, and into cholangiocyte-like cells, which formed duct-like cyst structures, expressed KRT19 and KRT7, and acquired epithelial polarity. In conclusion, this is the first report of the generation of proliferative and bipotential hepatic progenitor cells from hES cells. These hES cell–derived hepatic progenitor cells could be effectively used as an in vitro model for studying the mechanisms of hepatic stem/progenitor cell origin, self-renewal and differentiation

Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming

SummaryObtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2−/−/γc−/− mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications

Effects of oat (Avena sativa L.) hay diet supplementation on the intestinal microbiome and metabolome of Small-tail Han sheep

Supplementation of the sheep diet with oats (Avena sativa L.) improves animal growth and meat quality, however effects on intestinal microbes and their metabolites was not clear. This study aimed to establish the effect of dietary oat supplementation on rumen and colonic microbial abundance and explore the relationship with subsequent changes in digesta metabolites. Twenty Small-tail Han sheep were randomly assigned to a diet containing 30 g/100 g of maize straw (Control) or oat hay (Oat). After 90-days on experimental diets, rumen and colon digesta were collected and microbial diversity was determined by 16S rRNA gene Illumina NovaSeq sequencing and metabolomics was conducted using Ultra-high performance liquid chromatography Q-Exactive mass spectrometry (UHPLC-QE-MS). Compared to Control group, oat hay increased the abundance of Bacteroidetes and Fibrobacteres as well as known short-chain fatty acid (SCFA) producers Prevotellaceae, Ruminococcaceae and Fibrobacteraceae in rumen (p < 0.05). In rumen digesta, the Oat group showed had higher levels of (3Z,6Z)-3,6-nonadienal, Limonene-1,2-epoxide, P-tolualdehyde, and Salicylaldehyde compared to Control (p < 0.05) and these metabolites were positively correlated with the abundance of cecal Prevotellaceae NK3B31. In conclusion, supplementation of the sheep diet with oat hay improved desirable microbes and metabolites in the rumen, providing insight into mechanisms whereby meat quality can be improved by oat hay supplementation

Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Necessary and Sufficient Conditions for the Existence of a Hermitian Positive Definite Solution of a Type of Nonlinear Matrix Equations

We study the Hermitian positive definite solutions of the nonlinear matrix equation X+A∗X−2A=I, where A is an n×n nonsingular matrix. Some necessary and sufficient conditions for the existence of a Hermitian positive definite solution of this equation are given. However, based on the necessary and sufficient conditions, some properties and the equivalent equations of X+A∗X−2A=I are presented while the matrix equation has a Hermitian positive definite solution

Experimental study on the influence of recycled aggregates on the mechanical properties of concrete

Construction solid waste has become an important environmental pollution source in the city, and the treatment and application of construction solid waste has become the focus of attention. Construction waste recycled aggregates have defects such as high water absorption and micro cracks, which affect its extensive application. In order to improve the utilization rate of recycled aggregates, the influence of different replacement rates of recycled aggregates on the mechanical properties of concrete is studied in this paper. The results show that with the increase of replacement rate of recycled aggregates, the 3-day, 7-day and 28-day compressive strength, splitting strength and cohesive force of concrete decrease gradually, but the mechanical properties of concrete decrease slowly at 3 days and 7 days, and decrease obviously at 28 days. Moreover, with the increase of replacement rate of recycled aggregates, the decline trend of mechanical properties is not obvious. Compared with natural aggregate concrete, the 28-day compressive strength, splitting strength and cohesive force of 100% recycled aggregate concrete are reduced by 16.1%, 20.1% and 18.1% respectively, but the mechanical properties meet the requirements of C30 concrete, which provides a reference for engineering application

Research on the Assessment Technology of Land Available for PV

Based on the high-resolution satellite image data, the information mining technology of the available surface elements of PV is studied, and the investigation of the available surface elements of PV in 98 counties and cities of South Hebei grid is realized. Based on the large-scale and high-resolution remote sensing data obtained by multi-source remote sensing data fusion technology, the depth-learning-based surface feature recognition technology for photovoltaic development is studied. Based on the method of automatic identification and artificial combination of depth-learning, it can identify the available ground elements (roof, water surface, road surface, dry beach, etc.), the available surface elements of PV in 98 counties and cities of Hebei South Grid were obtained. From the overall point of view, the photovoltaic land, the building occupies the main position, in the four cities are relatively high, are in the 6% ~ 15