Identification of a Novel 81-kDa Component of the Xenopus Origin Recognition Complex

The Xenopus origin recognition complex is essential for chromosomal DNA replication in cell-free extracts. We have immunopurified the Xenopus origin recognition complex with anti-Xorc2 antibodies and analyzed its composition and properties. Xorc2 (p63) is specifically associated with Xorc1 (p115) and up to four additional polypeptides (p81, p78, p45, and p40). The cDNA encoding p81 is highly homologous to various expressed sequence tags from humans and mice encoding a protein of previously unknown function. Immunodepletion of p81 from Xenopus egg extracts, which also results in the removal of Xorc2, completely abolishes chromosomal DNA replication. Thus, p81 appears to play a crucial role at S phase in higher eukaryotes

Negative Cell Cycle Regulation and DNA Damage-inducible Phosphorylation of the BRCT Protein 53BP1

In a screen designed to discover suppressors of mitotic catastrophe, we identified the Xenopus ortholog of 53BP1 (X53BP1), a BRCT protein previously identified in humans through its ability to bind the p53 tumor suppressor. X53BP1 transcripts are highly expressed in ovaries, and the protein interacts with Xp53 throughout the cell cycle in embryonic extracts. However, no interaction between X53BP1 and Xp53 can be detected in somatic cells, suggesting that the association between the two proteins may be developmentally regulated. X53BP1 is modified via phosphorylation in a DNA damage-dependent manner that correlates with the dispersal of X53BP1 into multiple foci throughout the nucleus in somatic cells. Thus, X53BP1 can be classified as a novel participant in the DNA damage response pathway. We demonstrate that X53BP1 and its human ortholog can serve as good substrates in vitro as well as in vivo for the ATM kinase. Collectively, our results reveal that 53BP1 plays an important role in the checkpoint response to DNA damage, possibly in collaboration with ATM

Electronic Footprints in the Sand: Technologies for Assisting Domestic Violence Survivors

With the rapid growth and spread of Internet-based social support systems, the impact that these systems can make to society – be it good or bad – has become more significant and can make a real difference to people’s lives. As such, various aspects of these systems need to be carefully investigated and analysed, including their security/privacy issues. In this paper, we present our work in designing and implementing various technological features that can be used to assist domestic violence survivors in obtaining help without leaving traces which might lead to further violence from their abuser. This case study serves as the core of our paper, in which we outline our approach, various de- sign considerations – including difficulties in keeping browsing history private, our currently implemented solutions (single use URL, targeted history sanitita- tion agent, and secret graphical gateway), as well as novel ideas for future work (including location-based service advertising and deployment in the wild)

Complete mitochondrial genome of the green-lipped mussel, Perna canaliculus (Mollusca: Mytiloidea), from long nanopore sequencing reads

We describe here the first complete genome assembly of the New Zealand green-lipped mussel, Perna canaliculus, mitochondrion. The assembly was performed de novo from a mix of long nanopore sequencing reads and short sequencing reads. The genome is 16,005 bp long. Comparison to other Mytiloidea mitochondrial genomes indicates important gene rearrangements in this family

Keeping an eye on decellularized corneas: a review of methods, characterization and applications

The worldwide limited availability of suitable corneal donor tissue has led to the development of alternatives, including keratoprostheses (Kpros) and tissue engineered (TE) constructs. Despite advances in bioscaffold design, there is yet to be a corneal equivalent that effectively mimics both the native tissue ultrastructure and biomechanical properties. Human decellularized corneas (DCs) could offer a safe, sustainable source of corneal tissue, increasing the donor pool and potentially reducing the risk of immune rejection after corneal graft surgery. Appropriate, human-specific, decellularization techniques and high-resolution, non-destructive analysis systems are required to ensure reproducible outputs can be achieved. If robust treatment and characterization processes can be developed, DCs could offer a supplement to the donor corneal pool, alongside superior cell culture systems for pharmacology, toxicology and drug discovery studies

Was Sinn Féin dying? A quantitative post-mortem of the party's decline and the emergence of Fianna Fáil

This article calls for a reappraisal of the consensus surrounding the split within Sinn Féin in 1926 that led to the foundation of Fianna Fáil. It demonstrates that quantitative factors cited to demonstrate Sinn Féin’s “terminal” decline – finances, cumann numbers, and election results – and to explain de Valera’s decision to leave Sinn Féin and establish a rival republican organisation, Fianna Fáil, do not provide sufficient objective grounds to explain the republican leader’s actions. This article demonstrates that Sinn Féin’s election results during the period in question (1923-1926) were encouraging and the decline in finances and cumann numbers can be explained by the fact that the base year used to compare progress was 1923, an election year. Moreover, this article compares the performance of Sinn Féin to the first five years of Fianna Fáil (1926-1931) to show that what has been interpreted as terminal decline can also be attributed to normal inter-election lulls in party activity. Correspondingly, subjective factors – e.g. personal rivalries, differences in ideology, organisational style and levels of patience in terms of achieving political power – were most likely the determining factors rather than organisational decline

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Tissue is the issue-sarcoidosis following ABVD chemotherapy for Hodgkin's lymphoma: a case report

Thirty two year old Caucasian female presented 2 months post partum with fevers, cough and shortness of breath. CT scan of the chest to rule out pulmonary embolism revealed mediastinal lymphadenopathy. Biopsy of the nodes revealed classic Hodgkin's lymphoma and she received ABVD chemotherapy. She was in remission as confirmed by a PET/CT scan. Five months later she had another PET/CT scan which showed areas of hypermetabolism indicating a possible relapse. Biopsy revealed sarcoidosis. She received steroids and 18 months later remained in clinical remission. This rare case of sarcoid following classic Hodgkin's lymphoma illustrates that clinical presentation, physical exam, lab investigations and even PET/CT scans may not be able to discriminate between Hodgkin's lymphoma and sarcoidosis. Tissue biopsy and pathological diagnosis remain the gold standard

Mapping Children's Discussions of Evidence in Science to Assess Collaboration and Argumentation

The research reported in this paper concerns the development of children's skills of interpreting and evaluating evidence in science. Previous studies have shown that school teaching often places limited emphasis on the development of these skills, which are necessary for children to engage in scientific debate and decision-making. The research, undertaken in the UK, involved four collaborative decision-making activities to stimulate group discussion, each was carried out with five groups of four children (10-11 years old). The research shows how the children evaluated evidence for possible choices and judged whether their evidence was sufficient to support a particular conclusion or the rejection of alternative conclusions. A mapping technique was developed to analyse the discussions and identify different "levels" of argumentation. The authors conclude that suitable collaborative activities that focus on the discussion of evidence can be developed to exercise children's ability to argue effectively in making decisions