catena-Poly[[diaqua­nickel(II)]-μ-7-oxabicyclo­[2.2.1]heptane-2,3-di­carboxyl­ato]

In the crystal structure of the title compound, [Ni(C8H8O5)(H2O)2]n, the NiII cation is in a Jahn–Teller-distorted octahedral coordination environment binding to two O atoms from water molecules, the bridging O atom of the bicycloheptane unit, two carboxylate O atoms from different carboxylate groups and one carboxylate O atom from a symmetry-related bridging ligand. The crystal structure is made up from layers propagating parallel to the bc plane

Diaqua­bis(ciprofloxacinato)manganese(II) 2,2′-bipyridine solvate tetrahydrate

In the crystal structure of the title compound {systematic name: diaquabis­[1-cyclo­propyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro­quinoline-3-carboxyl­ato]manganese(II) 2,2′-bi­pyridine solvate tetrahydrate}, [Mn(C17H17FN3O3)2(H2O)2]·C10H8N2·4H2O, the pyridone O and one carboxyl­ate O atom of the two ciprofloxacin ligands are bound to the MnII ion and occupy the equatorial positions, while the two aqua O atoms lie in the apical positions resulting in a distorted octa­hedral geometry. The crystal packing is stabilized by N–H⋯O and O–H⋯O hydrogen bonding interactions

Common DNA sequence variation influences 3-dimensional conformation of the human genome.

BACKGROUND:The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation. RESULTS:To address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk. CONCLUSION:Our results demonstrate that common DNA sequence variants can influence 3D chromatin conformation, pointing to a more pervasive role for 3D chromatin conformation in human phenotypic variation than previously recognized

A compendium of chromatin contact maps reveals spatially active regions in the human genome

The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues. We also discover genomic regions that exhibit unusually high levels of local chromatin interactions. These frequently interacting regions (FIREs) are enriched for super-enhancers and are near tissue specifically expressed genes. They display strong tissue-specificity in local chromatin interactions. Additionally, FIRE formation is partially dependent on CTCF and the Cohesin complex. We further show that FIREs can help annotate the function of non-coding sequence variants

The neural correlates of value hierarchies: a prospective typology based on personal value profiles of emerging adults

IntroductionValue hierarchies, as motivational goals anchored in the self-schema, may be correlated with spontaneous activity in the resting brain, especially those involving self-relevance. This study aims to investigate the neural correlates of value hierarchies from the perspective of typology.MethodsA total of 610 Chinese college students (30.31% women), aged 18 to 23, completed the personal values questionnaire and underwent resting-state functional magnetic resonance imaging.ResultsThe latent profile analysis revealed three personal value profiles: traditional social orientation, modernized orientation, and undifferentiated orientation. Neuroimaging results revealed that individuals with modernized orientation prioritized openness to change value, and this personal-focus is related to the higher low-frequency amplitude of the posterior insula; individuals with traditional social orientation prioritized self-transcendence and conservation values, and this social-focus is related to the stronger functional connectivity of the middle insula with the inferior temporal gyrus, temporal gyrus, posterior occipital cortex, and basal ganglia, as well as weaker functional connections within the right middle insula.DiscussionTaken together, these findings potentially indicate the intra-generational differentiation of contemporary Chinese emerging adults’ value hierarchies. At the neural level, these are correlated with brain activities involved in processing self- and other-relevance

The Role of RhoA in Neovascular-Related Functions of Endothelial Progenitor Cells Induced by AngiotensinⅡ

Background/Aims: Interference with endothelial progenitor cell (EPC) neovascularization is a novel therapeutic target for neovascular-related diseases. Angiotensin Ⅱ (Ang Ⅱ) was found to enhance new vessel formation and aggravated neovascular-related diseases. In this study, we investigated the effects of Ang Ⅱ on EPC neovascular-related functions and explored the underlying mechanisms. Methods: EPCs were cultured from bone marrow derived mononuclear cells. The effects of Ang Ⅱ on EPC proliferation, adhesion, migration, and in vitro tube formation were investigated using the MTT assay, adhesion assay, transwell chamber assay, and in vitro tube formation assay respectively. The underlying mechanisms were explored using Western blotting assay. Results: EPC adhesion, migration and in vitro tube formation were promoted by Ang Ⅱ, and the effects were reversed by RhoA/Rho-associated kinases (ROCK) signaling pathway inhibitors including C3 exoenzyme, GGTI-286 and Y-27632. The active form of RhoA was up-regulated by Ang Ⅱ and this effect was abolished by C3 exoenzyme. Moreover, RhoA silencing resulted in a notable inhibition of EPC adhesion, migration and in vitro tube formation, suggesting that RhoA activation played a pivotal role in Ang Ⅱ angiogenic effect. The results also demonstrated that phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun-NH2 kinase was elevated by Ang Ⅱ and attenuated by C3 exoenzyme, GGTI-286 and Y-27632. The enhancing effects of Ang Ⅱ on EPC adhesion, migration and in vitro vasculogenesis were reversed by p38 inhibitor SB202190 and JNK inhibitor SP600125. Conclusion: Ang Ⅱ may enhance EPC neovascular-related functions through activating RhoA/ ROCK and MAPK signaling pathway

Single-Cell Rna Sequencing Deconvolutes the in Vivo Heterogeneity of Human Bone Marrow-Derived Mesenchymal Stem Cells

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells that have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneity in vivo in humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271+ BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPRhi CD45low BM-MSCs within the CD271+ BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of the transcriptomes suggest that osteoblast precursors induce angiogenesis coupled with osteogenesis, and chondrocyte precursors have the potential to differentiate into myocytes. We also discovered transcripts for several clusters of differentiation (CD) markers that were either highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs, representing potential novel markers for human BM-MSC purification. This study is the first systematic in vivo dissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing an insight into the extent of their cellular heterogeneity and roles in maintaining bone homeostasis