Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions

BACKGROUND: Metastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1. METHODS: Gene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes. SIGNIFICANCE/CONCLUSION: This study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define "bona fide" Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions

Synthesis, Magnetic Anisotropy and Optical Properties of Preferred Oriented Zinc Ferrite Nanowire Arrays

Preferred oriented ZnFe2O4 nanowire arrays with an average diameter of 16 nm were fabricated by post-annealing of ZnFe2 nanowires within anodic aluminum oxide templates in atmosphere. Selected area electron diffraction and X-ray diffraction exhibit that the nanowires are in cubic spinel-type structure with a [110] preferred crystallite orientation. Magnetic measurement indicates that the as-prepared ZnFe2O4 nanowire arrays reveal uniaxial magnetic anisotropy, and the easy magnetization direction is parallel to the axis of nanowire. The optical properties show the ZnFe2O4 nanowire arrays give out 370–520 nm blue-violet light, and their UV absorption edge is around 700 nm. The estimated values of direct and indirect band gaps for the nanowires are 2.23 and 1.73 eV, respectively

GAMETOPHYTE DEFECTIVE 1, a Putative Subunit of RNases P/MRP, Is Essential for Female Gametogenesis and Male Competence in Arabidopsis

RNA biogenesis, including biosynthesis and maturation of rRNA, tRNA and mRNA, is a fundamental process that is critical for cell growth, division and differentiation. Previous studies showed that mutations in components involved in RNA biogenesis resulted in abnormalities in gametophyte and leaf development in Arabidopsis. In eukaryotes, RNases P/MRP (RNase mitochondrial RNA processing) are important ribonucleases that are responsible for processing of tRNA, and transcription of small non-coding RNAs. Here we report that Gametophyte Defective 1 (GAF1), a gene encoding a predicted protein subunit of RNases P/MRP, AtRPP30, plays a role in female gametophyte development and male competence. Embryo sacs were arrested at stages ranging from FG1 to FG7 in gaf1 mutant, suggesting that the progression of the gametophytic division during female gametogenesis was impaired in gaf1 mutant. In contrast, pollen development was not affected in gaf1. However, the fitness of the mutant pollen tube was weaker than that of the wild-type, leading to reduced transmission through the male gametes. GAF1 is featured as a typical RPP30 domain protein and interacts physically with AtPOP5, a homologue of RNases P/MRP subunit POP5 of yeast. Together, our data suggest that components of the RNases P/MRP family, such as RPP30, play important roles in gametophyte development and function in plants

HCV+ Hepatocytes Induce Human Regulatory CD4+ T Cells through the Production of TGF-β

Background: Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4 + regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. Methodology/Principal Findings: HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4 + T cells. The production of IFN-c was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4 + T cells in contact with Huh7.5-FL expressed an increased level of the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV + hepatocytes upregulated the production of TGF-b and blockade of TGF-b abrogated Treg phenotype and function. Conclusions/Significance: These results demonstrate that HCV infected hepatocytes are capable of directly inducing Tregs development and may contribute to impaired host T cell responses

Adaptation-Dependent Synchronous Activity Contributes to Receptive Field Size Change of Bullfrog Retinal Ganglion Cell

Nearby retinal ganglion cells of similar functional subtype have a tendency to discharge spikes in synchrony. The synchronized activity is involved in encoding some aspects of visual input. On the other hand, neurons always continuously adjust their activities in adaptation to some features of visual stimulation, including mean ambient light, contrast level, etc. Previous studies on adaptation were primarily focused on single neuronal activity, however, it is also intriguing to investigate the adaptation process in population neuronal activities. In the present study, by using multi-electrode recording system, we simultaneously recorded spike discharges from a group of dimming detectors (OFF-sustained type ganglion cells) in bullfrog retina. The changes in receptive field properties and synchronization strength during contrast adaptation were analyzed. It was found that, when perfused using normal Ringer's solution, single neuronal receptive field size was reduced during contrast adaptation, which was accompanied by weakening in synchronization strength between adjacent neurons' activities. When dopamine (1 µM) was applied, the adaptation-related receptive field area shrinkage and synchronization weakening were both eliminated. The activation of D1 receptor was involved in the adaptation-related modulation of synchronization and receptive field. Our results thus suggest that the size of single neuron's receptive field is positively related to the strength of its synchronized activity with its neighboring neurons, and the dopaminergic pathway is responsible for the modulation of receptive field property and synchronous activity of the ganglion cells during the adaptation process

Changes in Corneal Basal Epithelial Phenotypes in an Altered Basement Membrane

To examine the corneal epithelial phenotype in an altered basement membrane.Corneas from 9 patients with symptoms of continuous unstable corneal curvature (CUCC) were harvested by penetrating keratoplasty and subjected to histology examination and immunohistochemical staining with transactivating and N-terminally truncated pP63 transcript (ΔNp63), cytokeratin 3 (Krt3), ATP-binding cassette sub-family G member 2 (ABCG2), connexin 43 (CX43), p38 mitogen-activated protein kinases (p38MAPK), activating protein 2 (TFAP2), and extracellular signal-regulated kinase (Erk1/2) monoclonal antibodies. Positive immunostaining with ABCG2, p38MAPK, and TFAP2 monoclonal antibodies was observed in the basal epithelial cells of CUCC patients, and CX43 and ΔNp63 were detected in the full-thickness epithelial cells of CUCC patients.Our results indicate that alteration of the corneal basement membrane induces a de-differentiation-like phenotype in corneal basal epithelial cells

Tiny Sea Anemone from the Lower Cambrian of China

Background Abundant fossils from the Ediacaran and Cambrian showing cnidarian grade grossly suggest that cnidarian diversification occurred earlier than that of other eumetazoans. However, fossils of possible soft-bodied polyps are scanty and modern corals are dated back only to the Middle Triassic, although molecular phylogenetic results support the idea that anthozoans represent the first major branch of the Cnidaria. Because of difficulties in taxonomic assignments owing to imperfect preservation of fossil cnidarian candidates, little is known about forms ancestral to those of living groups. Methods and Findings We have analyzed the soft-bodied polypoid microfossils Eolympia pediculata gen. et sp. nov. from the lowest Cambrian Kuanchuanpu Formation in southern China by scanning electron microscopy and computer-aided microtomography after isolating fossils from sedimentary rocks by acetic acid maceration. The fossils, about a half mm in body size, are preserved with 18 mesenteries including directives bilaterally arranged, 18 tentacles and a stalk-like pedicle. The pedicle suggests a sexual life cycle, while asexual reproduction by transverse fission also is inferred by circumferential grooves on the body column. Conclusions The features found in the present fossils fall within the morphological spectrum of modern Hexacorallia excluding Ceriantharia, and thus Eolympia pediculata could be a stem member for this group. The fossils also demonstrate that basic features characterizing modern hexacorallians such as bilateral symmetry and the reproductive system have deep roots in the Early Cambrian.Funding was provided by the National Science Foundation of China (http://www.nsfc.gov.cn/) grants 40830208, 40602003, 50702005 to J. Han and D. G. Shu, and by MOST Special Fund from the State Key Laboratory of Continental Dynamics, Northwest University, China (http://sklcd.nwu.edu.cn/) to J. Han and D. G. Shu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Inferring the Population Expansions in Peopling of Japan

Background: Extensive studies in different fields have been performed to reconstruct the prehistory of populations in the Japanese archipelago. Estimates the ancestral population dynamics based on Japanese molecular sequences can extend our understanding about the colonization of Japan and the ethnogenesis of modern Japanese. Methodology/Principal Findings: We applied Bayesian skyline plot (BSP) with a dataset based on 952 Japanese mitochondrial DNA (mtDNA) genomes to depict the female effective population size (Nef) through time for the total Japanese and each of the major mtDNA haplogroups in Japanese. Our results revealed a rapid N ef growth since,5 thousand years ago had left,72 % Japanese mtDNA lineages with a salient signature. The BSP for the major mtDNA haplogroups indicated some different demographic history. Conclusions/Significance: The results suggested that the rapid population expansion acted as a major force in shaping current maternal pool of Japanese. It supported a model for population dynamics in Japan in which the prehistoric population growth initiated in the Middle Jomon Period experienced a smooth and swift transition from Jomon to Yayoi, and then continued through the Yayoi Period. The confounding demographic backgrounds of different mtDN