141 research outputs found
A Ball-Milling-Enabled Cross-Electrophile Coupling
The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C–C bond formation was achieved in the absence of bulk solvent and air/moisture sensitive setups, in reaction times of 2 h. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the nickel catalytic cycle, enabling the synthesis of 28 cross-electrophile coupled products
Crossing media boundaries: adaptations and new media forms of the book
t is necessary to continuously review the definition of the book moving from one bound by its material form to one determined by its function as a means of communication. The book’s social function as the high status vehicle for communicating new ideas and cultural expressions is being challenged by sophisticated systems of conveying meaning in other media. In this article, we report on two projects: electronic book (e-book) publication and reader forum for Nature Mage and the transmedia augmented reality (AR) fiction Sherwood Rise, which investigate these issues. Claudio Pires Franco’s work is based on the adaptation of a source work: Duncan Pile’s Nature Mage. The project aims to develop the book from e-book to a fan-produced enhanced digital book. Through this practice-based research, Franco investigates the definitions and classification of the e and i forms of the book and adaptation in new media; the role of the author in creative collaboration with readers through online forums; the extension of the story world through creative collaboration and reader participation while respecting and safeguarding creative properties. One remove from the traditional book, David Miller’s Sherwood Rise, research the user experience with AR to examine narrative problems and explore new storytelling aesthetics. These new media forms define the outer borders of the book system within which content is formed and moulded, and around which society is shaped
A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples
In 5–40% of respiratory infections in children, the diagnostics
remain negative, suggesting that the patients might be infected with a yet
unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery
method based on recognition of restriction enzyme cleavage sites, ligation of
adaptors and subsequent amplification by PCR. However, direct discovery of
unknown pathogens in nasopharyngeal swabs is difficult due to the high
concentration of ribosomal RNA (rRNA) that acts as competitor. In the current
study we optimized VIDISCA by adjusting the reverse transcription enzymes and
decreasing rRNA amplification in the reverse transcription, using hexamer
oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA
templates was further reduced with oligonucleotides that anneal to rRNA but can
not be extended due to 3′-dideoxy-C6-modification. With these
modifications >90% reduction of rRNA amplification was established.
Further improvement of the VIDISCA sensitivity was obtained by high throughput
sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all
containing known respiratory viruses. We could identify the proper virus in the
majority of samples tested (11/18). The median load in the VIDISCA-454 positive
samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3–7.7 E6).
Our results show that optimization of VIDISCA and subsequent
high-throughput-sequencing enhances sensitivity drastically and provides the
opportunity to perform virus discovery directly in patient material
Cyclic AMP induces IPC leukemia cell apoptosis via CRE-and CDK-dependent Bim transcription
The IPC-81 cell line is derived from the transplantable BNML model of acute myelogenic leukemia (AML), known to be a reliable predictor of the clinical efficiency of antileukemic agents, like the first-line AML anthracycline drug daunorubicin (DNR). We show here that cAMP acted synergistically with DNR to induce IPC cell death. The DNR-induced death differed from that induced by cAMP by (1) not involving Bim induction, (2) being abrogated by GSK3β inhibitors, (3) by being promoted by the HSP90/p23 antagonist geldanamycin and truncated p23 and (4) by being insensitive to the CRE binding protein (CREB) antagonist ICER and to cyclin-dependent protein kinase (CDK) inhibitors. In contrast, the apoptosis induced by cAMP correlated tightly with Bim protein expression. It was abrogated by Bim (BCL2L11) downregulation, whether achieved by the CREB antagonist ICER, by CDK inhibitors, by Bim-directed RNAi, or by protein synthesis inhibitor. The forced expression of BimL killed IPC-81WT cells rapidly, Bcl2-overexpressing cells being partially resistant. The pivotal role of CREB and CDK activity for Bim transcription is unprecedented. It is also noteworthy that newly developed cAMP analogs specifically activating PKA isozyme I (PKA-I) were able to induce IPC cell apoptosis. Our findings support the notion that AML cells may possess targetable death pathways not exploited by common anti-cancer agents
The Mitochondrial Genome of the Lycophyte Huperzia squarrosa: The Most Archaic Form in Vascular Plants
Mitochondrial genomes have maintained some bacterial features despite their residence within eukaryotic cells for approximately two billion years. One of these features is the frequent presence of polycistronic operons. In land plants, however, it has been shown that all sequenced vascular plant chondromes lack large polycistronic operons while bryophyte chondromes have many of them. In this study, we provide the completely sequenced mitochondrial genome of a lycophyte, from Huperzia squarrosa, which is a member of the sister group to all other vascular plants. The genome, at a size of 413,530 base pairs, contains 66 genes and 32 group II introns. In addition, it has 69 pseudogene fragments for 24 of the 40 protein- and rRNA-coding genes. It represents the most archaic form of mitochondrial genomes of all vascular plants. In particular, it has one large conserved gene cluster containing up to 10 ribosomal protein genes, which likely represents a polycistronic operon but has been disrupted and greatly reduced in the chondromes of other vascular plants. It also has the least rearranged gene order in comparison to the chondromes of other vascular plants. The genome is ancestral in vascular plants in several other aspects: the gene content resembling those of charophytes and most bryophytes, all introns being cis-spliced, a low level of RNA editing, and lack of foreign DNA of chloroplast or nuclear origin
Determination of the Proteolytic Cleavage Sites of the Amyloid Precursor-Like Protein 2 by the Proteases ADAM10, BACE1 and γ-Secretase
Regulated intramembrane proteolysis of the amyloid precursor protein (APP) by the protease activities α-, β- and γ-secretase controls the generation of the neurotoxic amyloid β peptide. APLP2, the amyloid precursor-like protein 2, is a homolog of APP, which shows functional overlap with APP, but lacks an amyloid β domain. Compared to APP, less is known about the proteolytic processing of APLP2, in particular in neurons, and the cleavage sites have not yet been determined. APLP2 is cleaved by the β-secretase BACE1 and additionally by an α-secretase activity. The two metalloproteases ADAM10 and ADAM17 have been suggested as candidate APLP2 α-secretases in cell lines. Here, we used RNA interference and found that ADAM10, but not ADAM17, is required for the constitutive α-secretase cleavage of APLP2 in HEK293 and SH-SY5Y cells. Likewise, in primary murine neurons knock-down of ADAM10 suppressed APLP2 α-secretase cleavage. Using mass spectrometry we determined the proteolytic cleavage sites in the APLP2 sequence. ADAM10 was found to cleave APLP2 after arginine 670, whereas BACE1 cleaves after leucine 659. Both cleavage sites are located in close proximity to the membrane. γ-secretase cleavage was found to occur at different peptide bonds between alanine 694 and valine 700, which is close to the N-terminus of the predicted APLP2 transmembrane domain. Determination of the APLP2 cleavage sites enables functional studies of the different APLP2 ectodomain fragments and the production of cleavage-site specific antibodies for APLP2, which may be used for biomarker development
Changing relationships between multinational companies and their host regions? A case study of Aberdeen and the international oil industry
There has been a revival of interest in recent years in the relationships between multinational corporations (hereafter MNCs) and the host regions in which they operate. The branch plant thesis which generally views inward investment by MNCs in a negative light - as reinforcing power relations between core and peripheral regions - has been challenged, with the suggestion that such developments can play a key role in linking up local economies to important flows of knowledge and information in a global economy. It has also been suggested that MNC branch plant activities are in practice often upgraded over time, leading to the development of important competitive advantage's for host regions. In this paper, such claims are investigated through a case study of the Aberdeen oil region in the north east of Scotland. The changing position of Aberdeen within the oil industry's corporate division of labour is evaluated in terms of the wider theoretical debate
A Systematic Analysis of Cell Cycle Regulators in Yeast Reveals That Most Factors Act Independently of Cell Size to Control Initiation of Division
Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms
The evolutionary significance of polyploidy
Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often been considered to be an evolutionary 'dead end'. Here, we review the accumulating evidence that correlates polyploidization with environmental change or stress, and that has led to an increased recognition of its short-term adaptive potential. In addition, we discuss how, once polyploidy has been established, the unique retention profile of duplicated genes following whole-genome duplication might explain key longer-term evolutionary transitions and a general increase in biological complexity
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