The cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14

Mastoparan (MP) peptides, distributed in insect venoms, induce a local inflammatory response post envenomation. Most endogenous MPs share common structural elements within a tetradecapeptide sequence that adopts an amphipathic helix whilst traversing biological membranes and when bound to an intracellular protein target. Rational modifications to increase cationic charge density and amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide and potent secretagogue. Following intracellular translocation, MitP is accreted by mitochondria thus indicating additional utility as an antimicrobial agent. Hence, the objectives of this study were to compare the antimicrobial activities of a structurally diverse set of cationic cell penetrating peptides, including both MP and MitP sequences, and to chemically engineer analogues of MitP for potential therapeutic applications. Herein, we confirm that, like MP, MitP is a privileged structure for the development of antimicrobial peptides active against both prokaryotic and eukaryotic pathogens. Collectively, MitP and target-selective chimeric analogues are broad spectrum antibiotics, with the Gram-negative A. baumannii demonstrating particular susceptibility. Modifications of MitP by amino acid substitution at position-14 produced peptides, Δ14MitP analogues, with unique pharmacodynamic properties. One example, [Ser14]MitP, lacks both cytotoxicity against human cell lines and mast cell secretory activity yet retains selective activity against the encapsulated yeast C. neoformans

Comment on "Interaction of a Bose-Einstein condensate with a gravitational wave"

A gravitational-wave (GW) detector that utilizes the phononic excitations of a Bose-Einstein condensate (BEC) has recently been proposed [NJP 16, 085003 (2014)]. A subsequent and independent study, [arXiv:1807.07046v1], has suggested an alternative GW detection scheme that also uses phonons of a BEC but which was found to be many orders of magnitude away from being feasible. Here we make clear that the two proposed schemes are very different and that the conclusions of [arXiv:1807.07046v1] do not apply to the original proposal [NJP 16, 085003 (2014)].Comment: 3 page

Active Interferometry with Gaussian Channels

We consider an interferometer that contains active elements, such as a parametric amplifier, with general two-mode Gaussian unitary channels rather than the usually considered phase-shift channel. We concentrate on a scheme based on the recently proposed pumped-up SU(1,1) active interferometer where all input particles participate in the parameter estimation, and from which a conventional SU(1,1) interferometer is a limiting case. Using the covariance matrix formalism, we derive the quantum Fisher information of this active interferometer with a general two-mode Gaussian unitary channel, as well as the sensitivity for a number-sum measurement scheme, finding simple expressions for the latter. As an example application, we apply our results to Bose-Einstein condensates (BECs), and in particular a BEC gravitational-wave detector based on resonance, finding that the sensitivity of the detector can be improved by several orders of magnitude with this new interferometry scheme.Comment: 17 pages, 1 figur

Quantum simulation of dark energy candidates

Additional scalar fields from scalar-tensor, modified gravity or higher dimensional theories beyond general relativity may account for dark energy and the accelerating expansion of the Universe. These theories have lead to proposed models of screening mechanisms, such as chameleon and symmetron fields, to account for the tight experimental bounds on fifth-force searches. Cold atom systems have been very successfully used to constrain the parameters of these screening models, and may in future eliminate the interesting parameter space of some models entirely. In this paper, we show how to manipulate a Bose-Einstein condensate to simulate the effect of any screened scalar field model coupled conformally to the metric. We give explicit expressions for the simulation of various common models. This result may be useful for investigating the computationally challenging evolution of particles on a screened scalar field background, as well as for testing the metrology scheme of an upcoming detector proposal.Comment: 26 pages, 3 figure

Return to Siberia: The 2008 Kotuykan River Expedition

In the September-October 2007 issue of'The Earth Observer [volume 19, Number 4, pp. 13-21] we presented an article entitled "Expedition to Siberia: A Firsthand Account." In that article we shared excerpts from a blog that chronicled the adventures of a team of scientists from NASA and Russia's Academy of Science as they embarked on a three-week adventure in the wilds of Siberia in hopes of collecting measurements to validate data from satellites flying 700 km overhead. The same team, plus a couple new participants, headed back to Siberia this past sumner and we are now pleased to present the continuation of their story. For more background details on the expedition to Siberia or if you missed the first part of the story, please refer to the previous article

Mitoparans: mitochondriotoxic cell penetrating peptides and novel inducers of apoptosis.

Acknowledgments The authors would like to thank Keith Holding at the University of Wolverhampton for his outstanding technical support. This work was supported in part by Samantha Dickson Brain Tumour Trust.Introduction: The amphipathic helical peptide mastoparan (MP; H-INLKALAALAKKIL-NH2) inserts into biological membranes to modulate the activity of heterotrimeric G proteins and other targets. Moreover, whilst cell free models of apoptosis demonstrate MP to facilitate mitochondrial permeability transition and release of apoptogenic cytochrome c, MP-induced death of intact cells has been attributed to its non-specific membrane destabilising properties (necrotic mechanisms). However, MP and related peptides are known to activate other signalling systems, including p42/p44 MAP kinases and could therefore, also modulate cell fate and specific apoptotic events. The ability of MP to facilitate mitochondrial permeability in cell free systems has lead to proposals that MP could be of utility in tumour therapeutics provided that it conferred features of cellular penetration and mitochondrial localization. We have recently reported that our highly potent amphipathic MP analogue mitoparan (mitP; [Lys5,8Aib10]MP; Aib = -aminoisobutyric acid) specifically promotes apoptosis of human cancer cells, as was confirmed by in situ TUNEL staining and activation of caspase-3. Moreover, we have also demonstrated that mitP penetrates plasma membranes and redistributes to co-localize with mitochondria. Complementary studies, using isolated mitochondria, further demonstrated that mitP, through co-operation with a protein of the permeability transition pore complex voltage-dependent anion channel (VDAC), induced swelling and permeabilization of mitochondria, leading to the release of the apoptogenic factor cytochrome c. An expanding field of peptide and cell penetrating peptide (CPP) research has focussed on the selective targeting of tumours by engineering constructs that incorporate cell-specific or tissue–specific address motifs. Peptidyl address motifs could enhance the selectivity of drug delivery whilst the improved cellular uptake offered by CPP enhances bioavailability. Thus and as a potential therapeutic strategy, we extended our findings to design target-specific mitP analogues. The integrin-specific address motif RGD and a Fas ligand mimetic WEWT were incorporated by N-terminal acylation of mitP to produce novel tandem-linked chimeric peptides

Expedition to Siberia: A Firsthand Account

Nowhere on Earth is warming faster than the Arctic. In northern Siberia, average temperatures have risen 3-5 deg F over the past 30 years, whereas the worldwide average increase in that time is 1 deg F. Betweeen July 28 and August 12, 2007, a small international team of remote sensing and forest ecosystem scientists from NASA and Russia's Academy of Science set off on a three-week scientific expedition through the heart of the remote, wild forests of Siberia. They traveled southward down the Kochechum River observing the gradual transition from tundra to taiga, taking inventory of plant species along the way, and making ground-truth measurements to validate data being collected by several NASA satellites flying 700 kilometers overhead

Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.

OBJECTIVE: Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. RESULTS: In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L-1, MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes

Bino Dark Matter and Big Bang Nucleosynthesis in the Constrained E6SSM with Massless Inert Singlinos

We discuss a new variant of the E6 inspired supersymmetric standard model (E6SSM) in which the two inert singlinos are exactly massless and the dark matter candidate has a dominant bino component. A successful relic density is achieved via a novel mechanism in which the bino scatters inelastically into heavier inert Higgsinos during the time of thermal freeze-out. The two massless inert singlinos contribute to the effective number of neutrino species at the time of Big Bang Nucleosynthesis, where the precise contribution depends on the mass of the Z' which keeps them in equilibrium. For example for mZ' > 1300 GeV we find Neff \approx 3.2, where the smallness of the additional contribution is due to entropy dilution. We study a few benchmark points in the constrained E6SSM with massless inert singlinos to illustrate this new scenario.Comment: 24 pages, revised for publication in JHE

Multi-Sensor Remote Sensing of Forest Dynamics in Central Siberia

The forested regions of Siberia, Russia are vast and contain about a quarter of the world's forests that have not experienced harvesting. However, many Siberian forests are facing twin pressures of rapidly changing climate and increasing timber harvest activity. Monitoring the dynamics and mapping the structural parameters of the forest is important for understanding the causes and consequences of changes observed in these areas. Because of the inaccessibility and large extent of this forest, remote sensing data can play an important role for observing forest state and change. In Central Siberia, multi-sensor remote sensing data have been used to monitor forest disturbances and to map above-ground biomass from the Sayan Mountains in the south to the taiga-tundra boundaries in the north. Radar images from the Shuttle Imaging Radar-C (SIR-C)/XSAR mission were used for forest biomass estimation in the Sayan Mountains. Radar images from the Japanese Earth Resources Satellite-1 (JERS-1), European Remote Sensing Satellite-1 (ERS-1) and Canada's RADARSAT-1, and data from ETM+ on-board Landsat-7 were used to characterize forest disturbances from logging, fire, and insect damage in Boguchany and Priangare areas