Modulation of inositol polyphosphate levels regulates neuronal differentiation

The binding of neurotrophins to tropomyosin receptor kinase receptors initiates several signaling pathways, including the activation of phospholipase C-γ, which promotes the release of diacylglycerol and inositol 1,4,5-trisphosphate (IP3). In addition to recycling back to inositol, IP3 serves as a precursor for the synthesis of higher phosphorylated inositols, such as inositol 1,3,4,5,6-pentakisphosphate (IP5) and inositol hexakisphosphate (IP6). Previous studies on the effect of neurotrophins on inositol signaling were limited to the analysis of IP 3 and its dephosphorylation products. Here we demonstrate that nerve growth factor (NGF) regulates the levels of IP5 and IP6 during PC12 differentiation. Furthermore, both NGF and brain-derived neurotrophic factor alter IP5 and IP6 intracellular ratio in differentiated PC12 cells and primary neurons. Neurotrophins specifically regulate the expression of IP5-2 kinase (IP5-2K), which phosphorylates IP5 into IP6. IP5-2K is rapidly induced after NGF treatment, but its transcriptional levels sharply decrease in fully differentiated PC12 cells. Reduction of IP5-2K protein levels by small interfering RNA has an effect on the early stages of PC12 cell differentiation, whereas fully differentiated cells are not affected. Conversely, perturbation of IP5-2K levels by overexpression suggests that both differentiated PC12 cells and sympathetic neurons require low levels of the enzyme for survival. Therefore maintaining appropriate intracellular levels of inositol polyphosphates is necessary for neuronal survival and differentiation. © 2013 Loss et al

Preparation of Quality Inositol Pyrophosphates

Myo-inositol is present in nature either unmodified or in more complex phosphorylated derivates. Of the latest, the two most abundant in eukaryotic cells are inositol pentakisphosphate (IP5) and inositol hexakisphosphate (phytic acid or IP6). IP5 and IP6 are the precursors of inositol pyrophosphate molecules that contain one or more pyrophosphate bonds1. Phosphorylation of IP6 generates diphoshoinositolpentakisphosphate (IP7 or PP-IP5) and bisdiphoshoinositoltetrakisphosphate (IP8 or (PP)2-IP4). Inositol pyrophosphates have been isolated from all eukaryotic organisms so far studied. In addition, the two distinct classes of enzymes responsible for inositol pyrophosphate synthesis are highly conserved throughout evolution2-4

Concurrent Security of Anonymous Credentials Light, Revisited

We revisit the concurrent security guarantees of the well-known Anonymous Credentials Light (ACL) scheme (Baldimtsi and Lysyanskaya, CCS\u2713). This scheme was originally proven secure when executed sequentially, and its concurrent security was left as an open problem. A later work of Benhamouda et al. (EUROCRYPT\u2721) gave an efficient attack on ACL when executed concurrently, seemingly resolving this question once and for all. In this work, we point out a subtle flaw in the attack of Benhamouda et al. on ACL and show, in spite of popular opinion, that it can be proven concurrently secure. Our modular proof in the algebraic group model uses an ID scheme as an intermediate step and leads to a major simplification of the complex security argument for Abe\u27s Blind Signature scheme by Kastner et al. (PKC\u2722)

Entanglement distillation using particle statistics

We extend the idea of entanglement concentration for pure states(Phys. Rev. Lett. {\bf 88}, 187903) to the case of mixed states. The scheme works only with particle statistics and local operations, without the need of any other interactions. We show that the maximally entangled state can be distilled out when the initial state is pure, otherwise the entanglement of the final state is less than one. The distillation efficiency is a product of the diagonal elements of the initial state, it takes the maximum 50%, the same as the case for pure states.Comment: 3 pages, 1 figur

Generation and Evolution of Spin Entanglement in NRQED

A complete analysis on the generation of spin entanglement from NRQED is presented. The results of entanglement are obtained with relativistic correction to the leading order of (v/c)^2. It is shown that to this order the degree of entanglement of a singlet state does not change under time evolution whereas the triplet state can change.Comment: 8 pages, 1 figure, to appear in Phys. Rev.

The Long-Term Public Health Impact of a Community-Based Participatory Research Project for Health Promotion Among Socially Disadvantaged Women—A Case Study Protocol

Introduction: Community-based participatory research (CBPR) is considered to be of high potential for health promotion among socially disadvantaged groups. However, the long-term implementation and transfer of these approaches remain challenging, and the public health impact they achieve is difficult to study. This also pertains to the potential health effects and cost-effectiveness of CBPR. This study protocol describes the follow-up case study (NU-BIG) after 15 years of the BIG project (movement as investment in health), a project to promote physical activity among socially disadvantaged women. Through a participatory approach, BIG empowers the addressed women to plan and implement low-threshold physical activity offers. Since the project started in 2005, it was transferred to 17 communities in Germany. Materials and Analysis: NU-BIG intends to examine the long-term effects, including economic aspects, of the BIG project on individual and structural levels at all project sites, as well as its long-term implementation and transfer. NU-BIG is a cross-sectional and longitudinal study using a mixed method approach. For the longitudinal section, we re-analyze existing data from former BIG evaluations. For cross-sectional data collection, we use questionnaires and conduct qualitative interviews and focus groups. Women who take part in BIG program offers are part of the research team and will use the photo-voice approach to report on the effects of BIG. The study population consists of about 800 women who participate in BIG project offers and 50 persons involved in the implementation of the BIG project at local sites. Discussion: The expected results from NU-BIG are highly relevant for studying the long-term public health impact of CBPR. In particular, this project intends to answer questions on how the transfer of such projects can succeed and which factors determine if a CBPR project can be sustained at the community level. Eventually, these results can contribute to the further development of participatory approaches to provide effective health promotion among socially disadvantaged groups. Conclusion: Although CBPR is seen of having the potential to reduce health disparities, there is still a lack of research on its long-term effects and public health impact. NU-BIG aims at generating knowledge about the economic effects, reach, efficacy, adoption, implementation, and maintenance of a CBPR project. The expected results could be of high interest for BIG and other CBPR-projects

Sub-Telomere Directed Gene Expression during Initiation of Invasive Aspergillosis

Aspergillus fumigatus is a common mould whose spores are a component of the normal airborne flora. Immune dysfunction permits developmental growth of inhaled spores in the human lung causing aspergillosis, a significant threat to human health in the form of allergic, and life-threatening invasive infections. The success of A. fumigatus as a pathogen is unique among close phylogenetic relatives and is poorly characterised at the molecular level. Recent genome sequencing of several Aspergillus species provides an exceptional opportunity to analyse fungal virulence attributes within a genomic and evolutionary context. To identify genes preferentially expressed during adaptation to the mammalian host niche, we generated multiple gene expression profiles from minute samplings of A. fumigatus germlings during initiation of murine infection. They reveal a highly co-ordinated A. fumigatus gene expression programme, governing metabolic and physiological adaptation, which allows the organism to prosper within the mammalian niche. As functions of phylogenetic conservation and genetic locus, 28% and 30%, respectively, of the A. fumigatus subtelomeric and lineage-specific gene repertoires are induced relative to laboratory culture, and physically clustered genes including loci directing pseurotin, gliotoxin and siderophore biosyntheses are a prominent feature. Locationally biased A. fumigatus gene expression is not prompted by in vitro iron limitation, acid, alkaline, anaerobic or oxidative stress. However, subtelomeric gene expression is favoured following ex vivo neutrophil exposure and in comparative analyses of richly and poorly nourished laboratory cultured germlings. We found remarkable concordance between the A. fumigatus host-adaptation transcriptome and those resulting from in vitro iron depletion, alkaline shift, nitrogen starvation and loss of the methyltransferase LaeA. This first transcriptional snapshot of a fungal genome during initiation of mammalian infection provides the global perspective required to direct much-needed diagnostic and therapeutic strategies and reveals genome organisation and subtelomeric diversity as potential driving forces in the evolution of pathogenicity in the genus Aspergillus

Perturbation of pH and calcium signalling as a means to prevent Aspergillus fumigatus infection

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Identification of an Evolutionarily Conserved Family of Inorganic Polyphosphate Endopolyphosphatases

Inorganic polyphosphate (poly-P) consists of just a chain of phosphate groups linked by high energy bonds. It is found in every organism and is implicated in a wide variety of cellular processes (e.g. phosphate storage, blood coagulation, and pathogenicity). Its metabolism has been studied mainly in bacteria while remaining largely uncharacterized in eukaryotes. It has recently been suggested that poly-P metabolism is connected to that of highly phosphorylated inositol species (inositol pyrophosphates). Inositol pyrophosphates are molecules in which phosphate groups outnumber carbon atoms. Like poly-P they contain high energy bonds and play important roles in cell signaling. Here, we show that budding yeast mutants unable to produce inositol pyrophosphates have undetectable levels of poly-P. Our results suggest a prominent metabolic parallel between these two highly phosphorylated molecules. More importantly, we demonstrate that DDP1, encoding diadenosine and diphosphoinositol phosphohydrolase, possesses a robust poly-P endopolyphosphohydrolase activity. In addition, we prove that this is an evolutionarily conserved feature because mammalian Nudix hydrolase family members, the three Ddp1 homologues in human cells (DIPP1, DIPP2, and DIPP3), are also capable of degrading poly-P