Nanopore Device for Reversible Ion and Molecule Sensing or Migration

Disclosed are methods and devices for detection of ion migration and binding, utilizing a nanopipette adapted for use in an electrochemical sensing circuit. The nanopipette may be functionalized on its interior bore with metal chelators for binding and sensing metal ions or other specific binding molecules such as boronic acid for binding and sensing glucose. Such a functionalized nanopipette is comprised in an electrical sensor that detects when the nanopipette selectively and reversibly binds ions or small molecules. Also disclosed is a nanoreactor, comprising a nanopipette, for controlling precipitation in aqueous solutions by voltage-directed ion migration, wherein ions may be directed out of the interior bore by a repulsing charge in the bore

A novel secreted protein, MYR1, is central to Toxoplasma’s manipulation of host cells

The intracellular protozoan Toxoplasma gondii dramatically reprograms the transcriptome of host cells it infects, including substantially up-regulating the host oncogene c-myc. By applying a flow cytometry-based selection to infected mouse cells expressing green fluorescent protein fused to c-Myc (c-Myc–GFP), we isolated mutant tachyzoites defective in this host c-Myc up-regulation. Whole-genome sequencing of three such mutants led to the identification of MYR1 (Myc regulation 1; TGGT1_254470) as essential for c-Myc induction. MYR1 is a secreted protein that requires TgASP5 to be cleaved into two stable portions, both of which are ultimately found within the parasitophorous vacuole and at the parasitophorous vacuole membrane. Deletion of MYR1 revealed that in addition to its requirement for c-Myc up-regulation, the MYR1 protein is needed for the ability of Toxoplasma tachyzoites to modulate several other important host pathways, including those mediated by the dense granule effectors GRA16 and GRA24. This result, combined with its location at the parasitophorous vacuole membrane, suggested that MYR1 might be a component of the machinery that translocates Toxoplasma effectors from the parasitophorous vacuole into the host cytosol. Support for this possibility was obtained by showing that transit of GRA24 to the host nucleus is indeed MYR1-dependent. As predicted by this pleiotropic phenotype, parasites deficient in MYR1 were found to be severely attenuated in a mouse model of infection. We conclude, therefore, that MYR1 is a novel protein that plays a critical role in how Toxoplasma delivers effector proteins to the infected host cell and that this is crucial to virulence

Mid-Holocene, coral-based sea surface temperatures in the western tropical Atlantic

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial‐NoDerivs License. The definitive version was published in Rodriguez, L. G., Cohen, A. L., Ramirez, W., Oppo, D. W., Pourmand, A., Edwards, R. L., Alpert, A. E., & Mollica, N. Mid-Holocene, coral-based sea surface temperatures in the western tropical Atlantic. Paleoceanography and Paleoclimatology, 34(7), (2019): 1234-1245, doi:10.1029/2019PA003571.The Holocene is considered a period of relative climatic stability, but significant proxy data‐model discrepancies exist that preclude consensus regarding the postglacial global temperature trajectory. In particular, a mid‐Holocene Climatic Optimum, ~9,000 to ~5,000 years BP, is evident in Northern Hemisphere marine sediment records, but its absence from model simulations raises key questions about the ability of the models to accurately simulate climate and seasonal biases that may be present in the proxy records. Here we present new mid‐Holocene sea surface temperature (SST) data from the western tropical Atlantic, where twentieth‐century temperature variability and amplitude of warming track the twentieth‐century global ocean. Using a new coral thermometer Sr‐U, we first developed a temporal Sr‐U SST calibration from three modern Atlantic corals and validated the calibration against Sr‐U time series from a fourth modern coral. Two fossil corals from the Enriquillo Valley, Dominican Republic, were screened for diagenesis, U‐series dated to 5,199 ± 26 and 6,427 ± 81 years BP, respectively, and analyzed for Sr/Ca and U/Ca, generating two annually resolved Sr‐U SST records, 27 and 17 years long, respectively. Average SSTs from both corals were significantly cooler than in early instrumental (1870–1920) and late instrumental (1965–2016) periods at this site, by ~0.5 and ~0.75 °C, respectively, a result inconsistent with the extended mid‐Holocene warm period inferred from sediment records. A more complete sampling of Atlantic Holocene corals can resolve this issue with confidence and address questions related to multidecadal and longer‐term variability in Holocene Atlantic climate.This study was supported by NSF OCE 1747746 to Anne Cohen and by NSF OCE 1805618 to Anne Cohen and Delia Oppo. Eric Loss and his crew on Pangaea Exploration's Sea Dragon enabled fieldwork in Martinique, and George P. Lohman, Thomas DeCarlo, and Hanny Rivera assisted with coral coring. Kathryn Pietro and Julia Middleton assisted in the laboratory, and Louis Kerr provided technical support on the SEM at MBL. Gretchen Swarr provided technical support on the Element and iCap ICPMS at WHOI. We also thank Edwin Hernandez, Jose Morales, and Amos Winter for discussion. All data generated in this study will be made publicly available at http://www.ncdc.noaa.gov/data‐ access/paleoclimatology‐data/dataset

Vaccine potential of lena and lcpa proteins of leptospira interrogans in combination with escherichia coli heat-labile enterotoxin, b subunit (LTB)

Background and Objectives: Leptospirosis is a zooanthroponosis caused by the genus of Leptospira. It is an emerging public health problem due to its increasing incidence. The achievement to a vaccine that prevent from entrance of Leptospira interrogans to the deeper tissues of the host is needed. This study aimed to investigate the immunogenicity of LcpA (rLcpA) and LenA (rLenA) recombinant proteins in combination with LTB (rLTB) recombinant protein as an adjuvant against leptospiral infection in hamsters. Materials and Methods: The genes encoding these proteins were cloned into pGH cloning vector and then lenA, lcpA and ltb genes subcloned into pET-15b and pET-28a expression vectors, respectively. The hamsters were immunized with the purified recombinant proteins and challenged with Leptospira interrogans for evaluation of their survival. The antibody responses to the recombinant proteins were determined by ELISA. Then, data entered into SPSS software. Statistical Kruskal-Wallis test was used to compare the significant differences among different groups. The groups with significant differences were further analyzed by post hoc tests. The p value < 0.05 statistically was considered significant. Results: Immunized hamsters with rLenA-plus-rLTB, rLcpA-plus-rLTB and rLenA-plus-rLcpA-plus-rLTB proteins showed 60, 74, and 80 survival rates, respectively. A significant amount of interleukin-17 (IL-17), interleukin-4 (IL-4) and gamma interferon (IFNγ) cytokines were produced in immunized hamsters. Conclusion: Based on our findings, rLcpA and rLenA proteins in combination with rLTB can protect the hamsters against L. interrogans and effectively induce a protective antibody response. Thus, these proteins can be used as an additional prophylactic tool against leptospira. © 2018, Tehran University of Medical Science. All rights reserved

Twelve thousand years of dust: The Holocene global dust cycle constrained by natural archives

Mineral dust plays an important role in the climate system by interacting with radiation, clouds, and biogeochemical cycles. In addition, natural archives show that the dust cycle experienced variability in the past in response to global and local climate change. The compilation of the DIRTMAP paleodust datasets in the last two decades provided a target for paleoclimate models that include the dust cycle, following a time slice approach. We propose an innovative framework to organize a paleodust dataset that moves on from the positive experience of DIRTMAP and takes into account new scientific challenges, by providing a concise and accessible dataset of temporally resolved records of dust mass accumulation rates and particle grain-size distributions. We consider data from ice cores, marine sediments, loess/paleosol sequences, lake sediments, and peat bogs for this compilation, with a temporal focus on the Holocene period. This global compilation allows investigation of the potential, uncertainties and confidence level of dust mass accumulation rates reconstructions, and highlights the importance of dust particle size information for accurate and quantitative reconstructions of the dust cycle. After applying criteria that help to establish that the data considered represent changes in dust deposition, 43 paleodust records have been identified, with the highest density of dust deposition data occurring in the North Atlantic region. Although the temporal evolution of dust in the North Atlantic appears consistent across several cores and suggest that minimum dust fluxes are likely observed during the Early to mid-Holocene period (6000–8000 years ago), the magnitude of dust fluxes in these observations is not fully consistent, suggesting that more work needs to be done to synthesize datasets for the Holocene. Based on the data compilation, we used the Community Earth System Model to estimate the mass balance and variability of the global dust cycle during the Holocene, with dust load ranging from 17.1 to 20.5 Tg between 2000 and 10 000 years ago, and a minimum in the Early to Mid-Holocene (6000–8000 years ago)

Klinische Effekte der katheterbasierten Nierennervenablation bei therapieresistenter Hypertonie

Background: High blood pressure is one of the most common chronic cardiovascular diseases. Despite a plethora of drugs to lower blood pressure, adequate blood pressure reduction cannot be achieved in many patients with high blood pressure. Ablation of the nerves of the renal arteries is used in these patients. Methods: Renal nerve ablation is a catheter-based, minimally-invasive method which, with the appropriate experience, is relatively easy to carry out, and has already demonstrated very promising results in patients with treatment-resistant hypertension. Results: The data presented in this article confirm that catheter-based renal nerve ablation, used in 38 patients with treatment-resistant hypertension, is a safe and highly effective method of achieving optimal blood pressure stabilisation. Conclusion: It remains to be seen whether the promising results of current studies will be confirmed in the long-term progress and lead to a reduction of cardiovascular morbidity and mortality