Conformational photoswitching of a synthetic peptide foldamer bound within a phospholipid bilayer

The dynamic properties of foldamers, synthetic molecules that mimic folded biomolecules, have mainly been explored in free solution.We report on the design, synthesis, and conformational behavior of photoresponsive foldamers bound in a phospholipid bilayer akin to a biological membrane phase. These molecules contain a chromophore, which can be switched between two configurations by different wavelengths of light, attached to a helical synthetic peptide that both promotes membrane insertion and communicates conformational change along its length. Light-induced structural changes in the chromophore are translated into global conformational changes, which are detected by monitoring the solid-state 19 F nuclear magnetic resonance signals of a remote fluorine-containing residue located 1 to 2 nanometers away. The behavior of the foldamers in the membrane phase is similar to that of analogous compounds in organic solvents

U-Pb SHRIMP zircon dating of andesite from the Dolomite area (NE Italy): geochronological evidence for the early onset of Permian Volcanism in the eastern part of the southern Alps

The Athesian Volcanic District (AVD), a thick sequence of andesitic to rhyolitic lava and ignimbrite, overlies both the Variscan basement of the Dolomites and, where present, the continental basal conglomerate of Upper Carboniferous(?) to Early Permian age. This volcanic activity is known to mark the margin of the intra-Pangea megashear system between Gondwana and Laurasia, the onset age of which is determined in this study. SHRIMP U-Pb dating on zircon from Ponte Gardena/Waidbruck (Isarco/Eisack valley) basaltic andesite yields an age of 290.7 ± 3 Ma, providing the oldest record of andesite volcanic activity yet documented in the AVD. Two younger dates (279.9 ± 3.3 and 278.6 ± 3.1 Ma) obtained for the andesitic necks of M. dei Ginepri (Eores/Aferer valley) and Col Quaterna (western Comelico), respectively, probably represent a second pulse of andesite magmatic activity. Near Chiusa/Klausen, the volcanoclastic deposits at the bottom of the Funes/Villnoss valley volcano-sedimentary complex only contain detrital zircons, dated at 469 ± 6 Ma; these probably derive from erosion of Paleozoic porphyroids. Other zircons from the same sediments and inherited cores of magmatic andesite crystals give Paleoproterozoic (1953.6 ± 22.1, 1834.6 ± 69.3, 1773.6 ± 25.1 Ma), Early Neoproterozoic (1015 ± 14 Ma) and Late Neoproterozoic (728.4 ± 9.6, 687.6 ± 7.6 Ma) ages. These ancient detrital and inherited zircon ages fit the model that envisages the Dolomite region as being tectonically coherent with Africa, at least until the Lower Permian

Laboratory Exposures to Staphylococcal Enterotoxin B

First report of symptoms after ocular exposure to staphylococcal enteroxin B in the laboratory is detailed

Glitches in rotating supersolids

Glitches, spin-up events in neutron stars, are of prime interest as they reveal properties of nuclear matter at subnuclear densities. We numerically investigate the glitch mechanism due to vortex unpinning using analogies between neutron stars and dipolar supersolids. We explore the vortex and crystal dynamics during a glitch and its dependence on the supersolid quality, providing a tool to study glitches from different radial depths of a neutron star. Benchmarking our theory against neutron star observations, our work will open a new avenue for the quantum simulation of stellar objects from Earth.Comment: 13 pages, 9 figure

Sanitary problems related to the presence of Ostreopsis spp. in the Mediterranean Sea: a multidisciplinary scientific approach

The increased presence of potentially toxic microalgae in the Mediterranean area is a matter of great concern. Since the end of the last century, microalgae of the genus Ostreopsis have been detected more and more frequently in the Italian coastal waters. The presence of Ostreopsis spp. has been accompanied by the presence of previously undetected marine biotoxins (palytoxins) into the ecosystem with the increased possibility of human exposure. In response to the urgent need for toxicity characterization of palytoxin and its congeners, an integrated study encompassing both in vitro and in vivo methods was performed

Observation of vortices and vortex stripes in a dipolar Bose-Einstein condensate

Quantized vortices are the prototypical feature of superfluidity. Pervasive in all natural systems, vortices are yet to be observed in dipolar quantum gases. Here, we exploit the anisotropic nature of the dipole-dipole interaction of a dysprosium Bose-Einstein condensate to induce angular symmetry breaking in an otherwise cylindrically symmetric pancake-shaped trap. Tilting the magnetic field towards the radial plane deforms the cloud into an ellipsoid through magnetostriction, which is then set into rotation. At stirring frequencies approaching the radial trap frequency, we observe the generation of dynamically unstable surface excitations, which cause angular momentum to be pumped into the system through vortices. Under continuous rotation, the vortices arrange into a stripe configuration along the field--in close corroboration with simulations--realizing a long sought-after prediction for dipolar vortices.Comment: 13 pages, 4+3 figure

Toxicity and pathophysiology of palytoxin congeners after intraperitoneal and aerosol administration in rats

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Toxicon 150 (2018): 235-250, doi:10.1016/j.toxicon.2018.06.067.Preparations of palytoxin (PLTX, derived from Japanese Palythoa tuberculosa) and the congeners 42-OH-PLTX (from Hawaiian P. toxica) and ovatoxin-a (isolated from a Japanese strain of Ostreopsis ovata), as well as a 50:50 mixture of PLTX and 42-OH-PLTX derived from Hawaiian P. tuberculosa were characterized as to their concentration, composition, in-vitro potency and interaction with an anti-PLTX monoclonal antibody (mAb), after which they were evaluated for lethality and pathophysiological effects by intraperitoneal (IP) and aerosol administration to rats. Once each preparation was characterized as to its toxin composition by LC-HRMS and normalized to a total PLTX/OVTX concentration using HPLC-UV, all four preparations showed similar potency towards mouse erythrocytes in the erythrocyte hemolysis assay and interactions with the anti-PLTX mAb. The IP LD50 values derived from these experiments (1-3 μg/kg for all) were consistent with published values, although some differences from the published literature were seen. The aerosol LD50 values (.03-.06 μg/kg) confirmed the exquisite potency of PLTX suggested by the literature. The pathophysiological effects of the different toxin preparations by IP and aerosol administration were similar, albeit with some differences. Most commonly affected tissues were the lungs, liver, heart, kidneys, salivary glands, and adrenal glands. Despite some differences, these results suggest commonalities in potency and mechanism of action among these PLTX congeners.This work was supported by the Defense Threat Reduction Agency, through the Joint Program Executive Office for Chemical and Biological Defense, Contract number CB10396. Additional support to DMA and DLK was provided by National Science Foundation (Grant OCE-1314642) and National Institutes of Health (NIEHS-1P50-ES021923-01) through the Woods Hole Center for Oceans and Human Health

Highly Sensitive Electrochemiluminescent Nanobiosensor for the Detection of Palytoxin

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STAT3 controls the long-term survival and phenotype of repair Schwann cells during nerve regeneration

After nerve injury, Schwann cells convert to a phenotype specialized to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signaling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role. It supports the long-term survival of repair Schwann cells and is required for the maintenance of repair Schwann cell properties. In contrast, STAT3 is less important for the initial generation of repair Schwann cells after injury. In repair Schwann cells, we find that Schwann cell STAT3 activation by Tyr705 phosphorylation is sustained during long-term denervation. STAT3 is required for maintaining autocrine Schwann cell survival signaling, and inactivation of Schwann cell STAT3 results in a striking loss of repair cells from chronically denervated distal stumps. STAT3 inactivation also results in abnormal morphology of repair cells and regeneration tracks, and failure to sustain expression of repair cell markers, including Shh, GDNF, and BDNF. Because Schwann cell development proceeds normally without STAT3, the function of this factor appears restricted to Schwann cells after injury. This identification of transcriptional mechanisms that support long-term survival and differentiation of repair cells will help identify, and eventually correct, the failures that lead to the deterioration of this important cell population.SIGNIFICANCE STATEMENT Although injured peripheral nerves contain repair Schwann cells that provide signals and spatial clues for promoting regeneration, the clinical outcome after nerve damage is frequently poor. A key reason for this is that, during the slow growth of axons through the proximal parts of injured nerves repair, Schwann cells gradually lose regeneration-supporting features and eventually die. Identification of signals that sustain repair cells is therefore an important goal. We have found that in mice the transcription factor STAT3 protects these cells from death and contributes to maintaining the molecular and morphological repair phenotype that promotes axonal regeneration. Defining the molecular mechanisms that maintain repair Schwann cells is an essential step toward developing therapeutic strategies that improve nerve regeneration and functional recovery