564 research outputs found
Equivalence of block sequences in Schreier spaces and their duals
We prove that any normalized block sequence in a Schreier space , of
arbitrary order , admits a subsequence equivalent to a
subsequence of the canonical basis of some Schreier space. The analogous result
is proved for dual spaces to Schreier spaces. Basing on these results, we
examine the structure of strictly singular operators on Schreier spaces and
show that there are many closed operator ideals on a Schreier
space of any order, its dual and bidual space.Comment: Corrected citatio
Potential role for PADI-mediated histone citrullination in preimplantation development.
BACKGROUND: The peptidylarginine deiminases (PADIs) convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated.
RESULTS: In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26) were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA) to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17.
CONCLUSIONS: Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is permissive for histone acetylation
High-throughput proteomic profiling of the fish liver following bacterial infection
Abstract Background High-throughput proteomics was used to determine the role of the fish liver in defense responses to bacterial infection. This was done using a rainbow trout (Oncorhynchus mykiss) model following infection with Aeromonas salmonicida, the causative agent of furunculosis. The vertebrate liver has multifaceted functions in innate immunity, metabolism, and growth; we hypothesize this tissue serves a dual role in supporting host defense in parallel to metabolic adjustments that promote effective immune function. While past studies have reported mRNA responses to A. salmonicida in salmonids, the impact of bacterial infection on the liver proteome remains uncharacterized in fish. Results Rainbow trout were injected with A. salmonicida or PBS (control) and liver extracted 48 h later for analysis on a hybrid quadrupole-Orbitrap mass spectrometer. A label-free method was used for protein abundance profiling, which revealed a strong innate immune response along with evidence to support parallel rewiring of metabolic and growth systems. 3076 proteins were initially identified against all proteins (n = 71,293 RefSeq proteins) annotated in a single high-quality rainbow trout reference genome, of which 2433 were maintained for analysis post-quality filtering. Among the 2433 proteins, 109 showed significant differential abundance following A. salmonicida challenge, including many upregulated complement system and acute phase response proteins, in addition to molecules with putative functions that may support metabolic re-adjustments. We also identified novel expansions in the complement system due to gene and whole genome duplication events in salmonid evolutionary history, including eight C3 proteins showing differential changes in abundance. Conclusions This study provides the first high-throughput proteomic examination of the fish liver in response to bacterial challenge, revealing novel markers for the host defense response, and evidence of metabolic remodeling in conjunction with activation of innate immunity
A Management Capacity Assessment of Selected Coral Reef Marine Protected Areas in the Caribbean
An ecological method for the sampling of nonverbal signalling behaviours of young children with profound and multiple learning disabilities (PMLD)
- Background: Profound and multiple learning disabilities (PMLD) are a complex range of disabilities that affect the general health and wellbeing of the individual and their capacity to interact and learn.
- Method: We developed a new methodology to capture the nonsymbolic signalling behaviours of children with PMLD within the context of a face-to-face interaction with a caregiver to provide analysis at a micro-level of descriptive detail incorporating the use of the ELAN digital video software.
- Conclusion: The signalling behaviours of participants in a natural, everyday interaction can be better understood with the use of this innovation in methodology, which is predicated on the ecology of communication. Recognition of the developmental ability of the participants is an integral factor within that ecology. The method presented establishes an advanced account of the modalities through which a child affected by PMLD is able to communicate
Hydrogen permeation through VPD and CVD tungsten films on palladium
Isobars and isotherms were measured for hydrogen permeation through porous tungsten films on palladium, activation energy values were calculated for various Pd-W systems. The analysis of the obtained data and its comparison with the ones for dense tungsten coatings are carried out.Представлено результати дослідження ізобар та ізотерм проникнення водню крізь пористі плівки вольфраму на паладії, визначені величини енергії активації водневої проникності у системах Pd-W. Проведено аналіз одержаних даних і порівняння з даними що до щільних вольфрамових покриттів.Представлены результаты исследований изобар и изотерм проникновения водорода через пористые пленки вольфрама на палладии, определены величины энергии активации водородопроницаемости в различных системах Pd-W. Проведен анализ полученных данных и сравнение с данными для плотных вольфрамовых покрытий
Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells.
Peptidylarginine deiminase IV (PADI4) catalyzes the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline, and this activity has been linked to the repression of a limited number of target genes. To broaden our knowledge of the regulatory potential of PADI4, we utilized chromatin immunoprecipitation coupled with promoter tiling array (ChIP-chip) analysis to more comprehensively investigate the range of PADI4 target genes across the genome in MCF-7 breast cancer cells. Results showed that PADI4 is enriched in gene promoter regions near transcription start sites (TSSs); and, surprisingly, this pattern of binding is primarily associated with actively transcribed genes. Computational analysis found potential binding sites for Elk-1, a member of the ETS oncogene family, to be highly enriched around PADI4 binding sites; and coimmunoprecipitation analysis then confirmed that Elk-1 physically associates with PADI4. To better understand how PADI4 may facilitate gene transactivation, we then show that PADI4 interacts with Elk-1 at the c-Fos promoter and that, following Epidermal Growth Factor (EGF) stimulation, PADI4 catalytic activity facilitates Elk-1 phosphorylation, histone H4 acetylation, and c-Fos transcriptional activation. These results define a novel role for PADI4 as a transcription factor co-activator
Status of Coral Reefs in the US Caribbean and Gulf of Mexico: Florida, Texas, Puerto Rico, US Virgin Islands and Navassa
The following report on the status of US Caribbean coral reef ecosystems has been summarised from more extensive reports submitted to the US Coral Reef Task Force (USCRTF) working group that implemented in 2000 ‘A National Program to Assess, Inventory, and Monitor US Coral Reef Ecosystems’. The more-lengthy reports are also the basis for the biennial-issued document, ‘Status and Trends of US Coral Reef Ecosystems’. Each author is a recognised technical expert with responsibility for monitoring and/or managing aspects of their respective coral reef ecosystems
Proteomic comparison of selective breeding and growth hormone transgenesis in fish:Unique pathways to enhanced growth
Open Access funded by Biotechnology and Biological Sciences Research CouncilPeer reviewedPublisher PD
Identification of PADI2 as a potential breast cancer biomarker and therapeutic target.
BACKGROUND: We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects.
METHODS: RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known subtype and HER2/ERBB2 status were evaluated. To examine PADI2 expression levels during breast cancer progression, the cell lines from the MCF10AT model were used. The efficacy of the PADI inhibitor, Cl-amidine, was tested in vitro using MCF10DCIS cells grown in 2D-monolayers and 3D-spheroids, and in vivo using MCF10DCIS tumor xenografts. Treated MCF10DCIS cells were examined by flow-cytometry to determine the extent of apoptosis and by RT2 Profiler PCR Cell Cycle Array to detect alterations in cell cycle associated genes.
RESULTS: We show by RNA-seq that PADI2 mRNA expression is highly correlated with HER2/ERBB2 (p = 2.2 x 106) in luminal breast cancer cell lines. Using the MCF10AT model of breast cancer progression, we then demonstrate that PADI2 expression increases during the transition of normal mammary epithelium to fully malignant breast carcinomas, with a strong peak of PADI2 expression and activity being observed in the MCF10DCIS cell line, which models human comedo-DCIS lesions. Next, we show that a PADI inhibitor, Cl-amidine, strongly suppresses the growth of MCF10DCIS monolayers and tumor spheroids in culture. We then carried out preclinical studies in nude (nu/nu) mice and found that Cl-amidine also suppressed the growth of xenografted MCF10DCIS tumors by more than 3-fold. Lastly, we performed cell cycle array analysis of Cl-amidine treated and control MCF10DCIS cells, and found that the PADI inhibitor strongly affects the expression of several cell cycle genes implicated in tumor progression, including p21, GADD45alpha, and Ki67.
CONCLUSION: Together, these results suggest that PADI2 may function as an important new biomarker for HER2/ERBB2+ tumors and that Cl-amidine represents a new candidate for breast cancer therapy
- …