Molecularly imprinted conductive polymers for controlled trafficking of neurotransmitters at solid–liquid interfaces

We realize a molecularly imprinted polymer (MIP) which is imprinted with the retinal neurotransmitter glutamate. The films prepared by electrochemical deposition have a smooth surface with a granular morphology as observed using an atomic force microscope. Multiple reflection attenuated total reflection infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) are used to chemically confirm the imprint of a neurotransmitter in the MIP at the solid–liquid and the solid–air interface, respectively. Fluorescence spectroscopy using the dye fluorescamine is used to monitor the changes in neurotransmitter concentration in various solvents induced by application of voltage to the MIP. By controlling neurotransmitter trafficking across a solid–liquid interface with voltage, we suggest the possibility of using such a neurotransmitter imprinted MIP for chemical stimulation of retinal neurons. The current state of the art approach to restore sight in certain cases of blindness is the replacement of damaged photoreceptors by a subretinal implant consisting of light-sensitive photodiodes. Thus a future perspective of our work would be to chemically stimulate the neurons by replacing the photodiodes in the subretinal implant by the neurotransmitter imprinted polymer film

Tomography of X-ray Nova Muscae 1991: Evidence for ongoing mass transfer and stream-disc overflow

We present a spectroscopic analysis of the black hole binary Nova Muscae 1991 in quiescence using data obtained in 2009 with MagE on the Magellan Clay telescope and in 2010 with IMACS on the Magellan Baade telescope at the Las Campanas Observatory. Emission from the disc is observed in H alpha, H beta and Ca II (8662 A). A prominent hotspot is observed in the Doppler maps of all three emission lines. The existence of this spot establishes ongoing mass transfer from the donor star in 2009-2010 and, given its absence in the 1993-1995 observations, demonstrates the presence of a variable hotspot in the system. We find the radial distance to the hotspot from the black hole to be consistent with the circularization radius. Our tomograms are suggestive of stream-disc overflow in the system. We also detect possible Ca II (8662 A) absorption from the donor star.Comment: 10 pages, 11 figures, 1 table. Accepted for publication in MNRA

Chemically induced dimerization modules as a platform for plant biosensor engineering

Protein biosensors for small molecules have important applications in agriculture, medicine, and security, but it remains difficult to rapidly produce a high-affinity sensor for a given ligand. This is partly due to two major challenges. First, most small molecule ligands have only a small number of residues with which a protein can make energetically favorable contacts, making it difficult to engineer high-affinity binding. Second, even if a high-affinity binding protein is engineered, it is difficult to transduce the binding event into an output. The majority of plant hormone perception occurs by chemically induced dimerization, where binding of the hormone to a soluble receptor causes a conformational change that allows the receptor to form a heterodimer with an interaction partner. These CID modules make an ideal platform for engineering small molecule biosensors because they naturally address the two primary challenges above: their unique architecture allows sensitive biosensors to be constructed from low-affinity receptors and protein dimerization provides a natural method of ligand binding transduction. The ability to engineer CID modules would lead directly to in planta biosensors and would also have broader applications to biosensor design in other biological systems. Here we describe the development of a general biosensor engineering platform using the abscisic acid receptor PYR1 of Arabidopsis thaliana, which was previously engineered to sense the agrochemical mandipropamid.1 We combine comprehensive mutagenesis2,3, high-throughput screening, deep sequencing, and machine learning to rapidly construct a model of the fitness landscape for binding of PYR1 to a specific ligand. We then use this model to design a targeted library to screen for higher affinity sensors. For high-throughput screening, we use both an established yeast two-hybrid (Y2H) screen and a novel yeast surface display (YSD) system. These techniques offer complementary advantages: Y2H is straightforward to implement and requires no purified protein, while YSD offers higher throughput and more stringent quantification of protein-protein interactions. Finally, we describe early development of two additional CID modules from the gibberellin and strigolactone sensing networks of A. thaliana. (1) Park, S.-Y.; Peterson, F. C.; Mosquna, A.; Yao, J.; Volkman, B. F.; Cutler, S. R. Agrochemical Control of Plant Water Use Using Engineered Abscisic Acid Receptors. Nature 2015, 520 (7548), 545–548. https://doi.org/10.1038/nature14123. (2) Wrenbeck, E. E.; Klesmith, J. R.; Stapleton, J. A.; Adeniran, A.; Tyo, K. E. J.; Whitehead, T. A. Plasmid-Based One-Pot Saturation Mutagenesis. Nat. Methods 2016, 13 (11), 928–930. https://doi.org/10.1038/nmeth.4029. (3) Medina-Cucurella, A. V.; Steiner, P. J.; Faber, M. S.; Beltrán, J.; Borelli, A. N.; Kirby, M. B.; Cutler, S. R.; Whitehead, T. A. User-Defined Single Pot Mutagenesis Using Unpurified Oligo Pools. Re

Seasonal dynamics of marine snow‐associated and free‐living demethylating bacterial communities in the coastal northern Adriatic Sea

The extent of DMSP demethylation has been hypothesized to depend on DMSP availability and bacterial sulfur demand, which might lead to niche differentiation of the demethylating bacterial community. In this study, we determined DMSP concentrations in marine snow and the ambient water over a seasonal cycle and linked DMSP concentrations to the abundance of bacteria harboring the demethylation dmdA gene in the Adriatic Sea. In marine snow, DMSP concentrations were up to four times higher than in the ambient water and three times higher in marine snow in summer than in winter. The average dmdA:recA gene ratio over the sampling period was 0.40 ± 0.24 in marine snow and 0.48 ± 0.21 in the ambient water. However, at the subclade level, differences in the demethylating bacterial community of marine snow and the ambient water were apparent. Seasonal patterns of potentially demethylating bacteria were best visible at the oligotype level. In the ambient water, the SAR116 and the OM60/NOR5 clade were composed of oligotypes that correlated to high DMSP concentrations, while oligotypes of the Rhodospirillales correlated to low DMSP concentrations. Our results revealed a pronounced seasonal variability and spatial heterogeneity in DMSP concentrations and the associated demethylating bacterial community

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)

Optically opaque color-flavor locked phase inside compact stars

The contribution of thermally excited electron-positron pairs to the bulk properties of the color-flavor locked quark phase inside compact stars is examined. The presence of these pairs causes the photon mean free path to be much smaller than a typical core radius ($R_0 \simeq 1$ km) for all temperatures above 25 keV so that the photon contribution to the thermal conductivity is much smaller than that of the Nambu-Goldstone bosons. We also find that the electrons and positrons dominate the electrical conductivity, while their contributions to the total thermal energy is negligible.Comment: 3 pages, 2 figures. Published versio

Cellular and Molecular Bases of the Initiation of Fever

All phases of lipopolysaccharide (LPS)-induced fever are mediated by prostaglandin (PG) E(2). It is known that the second febrile phase (which starts at ~1.5 h post-LPS) and subsequent phases are mediated by PGE(2) that originated in endotheliocytes and perivascular cells of the brain. However, the location and phenotypes of the cells that produce PGE(2) triggering the first febrile phase (which starts at ~0.5 h) remain unknown. By studying PGE(2) synthesis at the enzymatic level, we found that it was activated in the lung and liver, but not in the brain, at the onset of the first phase of LPS fever in rats. This activation involved phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) and transcriptional up-regulation of cyclooxygenase (COX)-2. The number of cells displaying COX-2 immunoreactivity surged in the lung and liver (but not in the brain) at the onset of fever, and the majority of these cells were identified as macrophages. When PGE(2) synthesis in the periphery was activated, the concentration of PGE(2) increased both in the venous blood (which collects PGE(2) from tissues) and arterial blood (which delivers PGE(2) to the brain). Most importantly, neutralization of circulating PGE(2) with an anti-PGE(2) antibody both delayed and attenuated LPS fever. It is concluded that fever is initiated by circulating PGE(2) synthesized by macrophages of the LPS-processing organs (lung and liver) via phosphorylation of cPLA(2) and transcriptional up-regulation of COX-2. Whether PGE(2) produced at the level of the blood–brain barrier also contributes to the development of the first phase remains to be clarified

Deafness and Orality: An Electronic Conversation

Processing Note: This is a symposium and has a lot of participants, listed as authors and recorded here in alphabetical order.AbstractNot

Multiwavelength study of the transient X-ray binary IGR J01583+6713

We have investigated multiband optical photometric variability and stability of the H$\alpha$ line profile of the transient X-ray binary IGR J01583+6713. We set an upper limit of 0.05 mag on photometric variations in the {\it V} band over a time scale of 3 months. The H$\alpha$ line is found to consist of non-Gaussian profile and quite stable for a duration of 2 months. We have identified the spectral type of the companion star to be B2 IVe while distance to the source is estimated to be $\sim$ 4.0 kpc. Along with the optical observations, we have also carried out analysis of X-ray data from three short observations of the source, two with the {\it Swift}--XRT and one with the {\it RXTE}--PCA. We have detected a variation in the absorption column density, from a value of 22.0 $\times$ 10$^{22}$ cm$^{-2}$ immediately after the outburst down to 2.6 $\times$ 10$^{22}$ cm$^{-2}$ four months afterwards. In the quiescent state, the X-ray absorption is consistent with the optical reddening measurement of E(B - V) = 1.46 mag. From one of the {\it Swift} observations, during which the X-ray intensity was higher, we have a possible pulse detection with a period of 469.2 s. For a Be X-ray binary, this indicates an orbital period in the range of 216--561 days for this binary system.Comment: 22 pages, 8 figures, accepted for publication in MNRA