Discovery of cell-type specific regulatory elements in the human genome using differential chromatin modification analysis

Chromatin modifications have been comprehensively illustrated to play important roles in gene regulation and cell diversity in recent years. Given the rapid accumulation of genome-wide chromatin modification maps across multiple cell types, there is an urgent need for computational methods to analyze multiple maps to reveal combinatorial modification patterns and define functional DNA elements, especially those are specific to cell types or tissues. In this current study, we developed a computational method using differential chromatin modification analysis (dCMA) to identify cell-type-specific genomic regions with distinctive chromatin modifications. We then apply this method to a public data set with modification profiles of nine marks for nine cell types to evaluate its effectiveness. We found cell-type-specific elements unique to each cell type investigated. These unique features show significant cell-type-specific biological relevance and tend to be located within functional regulatory elements. These results demonstrate the power of a differential comparative epigenomic strategy in deciphering the human genome and characterizing cell specificity.     

Arabidopsis Villins Promote Actin Turnover at Pollen Tube Tips and Facilitate the Construction of Actin Collars

Apical actin filaments are crucial for pollen tube tip growth. However, the specific dynamic changes and regulatory mechanisms associated with actin filaments in the apical region remain largely unknown. Here, we have investigated the quantitative dynamic parameters that underlie actin filament growth and disappearance in the apical regions of pollen tubes and identified villin as the major player that drives rapid turnover of actin filaments in this region. Downregulation of Arabidopsis thaliana VILLIN2 (VLN2) and VLN5 led to accumulation of actin filaments at the pollen tube apex. Careful analysis of single filament dynamics showed that the severing frequency significantly decreased, and the lifetime significantly increased in vln2 vln5 pollen tubes. These results indicate that villin-mediated severing is critical for turnover and departure of actin filaments originating in the apical region. Consequently, the construction of actin collars was affected in vln2 vln5 pollen tubes. In addition to the decrease in severing frequency, actin filaments also became wavy and buckled in the apical cytoplasm of vln2 vln5 pollen tubes. These results suggest that villin confers rigidity upon actin filaments. Furthermore, an observed decrease in skewness of actin filaments in the subapical region of vln2 vln5 pollen tubes suggests that villin-mediated bundling activity may also play a role in the construction of actin collars. Thus, our data suggest that villins promote actin turnover at pollen tube tips and facilitate the construction of actin collars.     

Use of Granulocyte Colony-Stimulating Factor for the Treatment of Thin Endometrium in Experimental Rats

Granulocyte colony-stimulating factor (G-CSF) induces stem cells to mobilize to the injury site, which have beneficial effect on tissue repair. The aim of this study was to investigate the effect of G-CSF on the thin endometrium in rat models. In the present study, rats with thin endometrium were divided into 4 groups (experimental group I: administrated with G-CSF (40 µg/kg/d) 4–6 hours post-modeling; control group I: administrated with saline 4–6 hours post-modeling; experimental group II: administrated with G-CSF (40 µg/kg/d) 12 days post-modeling; control group II: administrated with saline 12 days post-modeling. The agentia was given once daily and last for 5 days. Endometrial morphology was analyzed by Hematoxylin-Eosin staining, and the regeneration of endometrial cells was evaluated by immunohistochemistry and western-blot with cytokeratin and vimentin. We found that endometrial thickness and morphology presented a significant difference between experimental groups and control groups. No matter when we start with G-CSF, there was a significantly thicker endometrium and stronger expression of cytokeratin/vimintin in the experimental groups compared with the control groups (P<0.01). There were significant thicker endometrial lining and stronger expression of cytokeratin/vimintin in experimental group I than that of experimental group II (P<0.05), but there was no difference in the endometrial lining and the expression of cytokeratin/vimintin between the two control groups (P>0.05). In conclusion, G-CSF can promote the regeneration of endometrial cells in animal research, especially when the G-CSF was administrated earlier.     

步氏巨猿牙齿大小上的变异性和南方古猿类食性假说

步氏巨猿牙齿大小上的变异性表明,在柳城巨猿洞局部地区的堆积中可能有少量时代稍晚的巨猿牙齿标本。晚期步氏巨猿与早期的相比,后部齿显著增大而前部齿则无显著差异。从步氏巨猿牙齿在大小上的演化趋势来看,南非南方古猿类中的纤细类与粗壮类之间在齿列比例上的不同不一定意味着其食性上有大的差异,纤细类与粗壮类也未必有“属”这一分类级别上的差异。     

The Evolution of the Ribonucleotide Reductases: Much Ado About Oxygen

Ribonucleotide reduction is the only known biological means for de novo production of deoxyribonucleotides, the building blocks of DNA. These are produced from ribonucleotides, the building blocks of RNA, and the direction of this reaction has been taken to support the idea that, in evolution, RNA preceded DNA as genetic material. However, an understanding of the evolutionary relationships among the three modern-day classes of ribonucleotide reductase and how the first reductase arose early in evolution is still far off. We propose that the diversification of this class of enzymes is inherently tied to microbial colonization of aerobic and anaerobic niches. The work is of broader interest, as it also sheds light on the process of adaptation to oxygenic environments consequent to the evolution of atmospheric oxygen.     

AZD8835 inhibits osteoclastogenesis and periodontitis-induced alveolar bone loss in rats

Chronic periodontitis (CP) is one of the most common oral diseases, which is characterized by the loss of connective tissue and alveolar bone in adults. AZD8835, a novel dual phosphoinositide-3-kinase (PI3K) inhibitor, is currently in phase 1 clinical evaluation to treat breast cancer. However, whether AZD8835 has any effect on teeth and alveolar bone health remains unclear. In the current study, we aimed to investigate the potential effect of AZD8835 in treating CP in vitro and in vivo. We found that AZD8835 could inhibit osteoclast differentiation, bone resorption, and downregulate the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (Trap), cathepsin K (Ctsk), V-ATPase d2 (Atp6v0d2), and calcitonin receptor (Ctr). In addition, AZD8835 suppressed osteoclastogenesis by inhibiting receptor activator of nuclear factor kappa B ligand (RANKL)-induced PI3K/protein kinase B (AKT), extracellular signal-regulated kinase, and nuclear factor-κB signaling in BMMs. In vivo, AZD8835 greatly ameliorated alveolar bone (ABL) loss in rats with CP. Meanwhile, histological examination showed fewer osteoclasts in the treatment group. In conclusion, these results indicated that AZD8835 is a promising agent to reduce ABL in CP.