Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide

Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions

Lamin B1 controls oxidative stress responses via Oct-1

Interaction of lamins with chromatin and transcription factors regulate transcription. Oct-1 has previously been shown to colocalize partly with B-type lamins and is essential for transcriptional regulation of oxidative stress response genes. Using sequential extraction, co-immunoprecipitation (IP), fluorescence loss in photobleaching, and fluorescence resonance energy transfer, we confirm Oct-1–lamin B1 association at the nuclear periphery and show that this association is lost in Lmnb1Δ/Δ cells. We show that several Oct-1–dependent genes, including a subset involved in oxidative stress response, are dysregulated in Lmnb1Δ/Δ cells. Electrophoretic mobility shift assay and chromatin IP reveal that Oct-1 binds to the putative octamer-binding sequences of the dysregulated genes and that this activity is increased in cells lacking functional lamin B1. Like Oct1−/− cells, Lmnb1Δ/Δ cells have elevated levels of reactive oxygen species and are more susceptible to oxidative stress. Sequestration of Oct-1 at the nuclear periphery by lamin B1 may be a mechanism by which the nuclear envelope can regulate gene expression and contribute to the cellular response to stress, development, and aging

Stressors and threats to the flora of Acadia National Park, Maine: Current knowledge, information gaps, and future directions

Stressors and threats to the flora of Acadia National Park, Maine: Current knowledge, information gaps, and future directions. J. Torrey Bot. Soc. 139: 323–344. 2012.— Acadia National Park is a center of plant diversity in northeastern North America. The Park\u27s varied habitats and flora are sensitive to a number of natural and anthropogenic perturbations. Stressors such as invasive plants, pest and pathogens, ozone, acidic fog and sulfur deposition, nitrogen deposition, heavy metals, fire and fire suppression, over-browsing, visitor use, hurricanes, and climate change have all had effects on the Park\u27s habitats and plant species at some point and it is unclear how many of these stressors are currently affecting the flora of Acadia National Park. We discuss the botanical diversity of Acadia, assess the natural and anthropogenic stressors and threats affecting the Park\u27s flora, and summarize critical information gaps to better assess the known stressors and threats to the flora. Understanding these stressors and threats is critical to making informed management decisions to preserve the botanical diversity of Acadia and other regional parks

Impact of a catch-up strategy of DT-IPV vaccination during hospitalization on vaccination coverage among people over 65 years of age in france: The HOSPIVAC study (Vaccination during hospitalization)

In France, diphtheria tetanus and inactivated polio vaccine (DT-IPV) coverage and immunization are insufficient in the elderly and decrease with age. The principal objective of this study was to assess the impact of a strategy of catch-up DT-IPV vaccination during hospitalization in people over the age of 65 years in central France (the Sarthe region). We performed a prospective, single-center, cluster-randomized study (four hospital wards). We included patients aged ≥65 years, without mental impairment, contraindication and who accepted to participate, hospitalized in the internal medicine wards in Le Mans Hospital from 28 May 2018 to 27 May 2019. The DT-IPV vaccination status of the patients was determined at inclusion and the wards were randomized (intervention and control). In the intervention group, vaccination was up-dated during hospitalization. In case of temporary contraindication, vaccination was prescribed at hospital discharge. Patients hospitalized in the control wards received oral information only. Final immunization status was determined by calling the patient’s general practitioner two months after hospital discharge. One hundred and fifty seven patients were included: 73 in the intervention and 84 in the control arm. Baseline immunization coverage was 46.5%. Vaccination coverage increased from 56.2% to 80.8% in the intervention group and from 38.1% to 40.5% in the control group (p < 0.001). Having received sufficient information from the general practitioner was the only factor associated with vaccination being up-to-date in uni- and multivariate analysis: OR = 5.07 [2.45–10.51]. In a setting of low vaccination coverage DT-IPV vaccination during hospitalization is an effective catch-up strategy

HIV protease inhibitors inhibit FACE1/ ZMPSTE24: a mechanism for acquired lipodystrophy in patients on highly active antiretroviral therapy

Abstract HIV-PIs (HIV protease inhibitors) have proved to be of great benefit for the millions of people suffering from AIDS. However, one of the side effects of this component of combined highly active antiretroviral therapy is lipodystrophy, which affects a large number of the patients taking this class of drug. It has been shown that many of these protease inhibitors inhibit the ZMPSTE24 enzyme responsible for removing the farnesylated tail of prelamin A, which is a nuclear lamina component that has been implicated in some of the nuclear laminopathies. Build up of this protein somehow leads to acquired lipodystrophy, possibly through its interaction with a transcription factor called SREBP-1 (sterol-regulatory-element-binding protein-1). The downstream effect of this is altered fatty acid metabolism and sterol synthesis, which may cause lipodystrophy in patients. The build-up of this protein also appears to have morphological consequences on the nucleus and we reveal, by dual-axis electron tomography, a complex nucleoplasmic reticulum that forms after HIV-PI treatment as a result of acute farnesylated prelamin A accumulation. A greater understanding of the molecular mechanisms leading to lipodystrophy will hopefully facilitate the design of improved HIV-PIs that do not cause this debilitating side effect

Electromagnetic mixed waste processing system for asbestos decontamination

The overall objective of this three-phase program is to develop an integrated process for treating asbestos-containing material that is contaminated with radioactive and hazardous constituents. The integrated process will attempt to minimize processing and disposal costs. The objectives of Phase 1 were to establish the technical feasibility of asbestos decomposition, inorganic radionuclide nd heavy metal removal, and organic volatilization. Phase 1 resulted in the successful bench-scale demonstration of the elements required to develop a mixed waste treatment process for asbestos-containing material (ACM) contaminated with radioactive metals, heavy metals, and organics. Using the Phase 1 data, a conceptual process was developed. The Phase 2 program, currently in progress, is developing an integrated system design for ACM waste processing. The Phase 3 program will target demonstration of the mixed waste processing system at a DOE facility. The electromagnetic mixed waste processing system employs patented technologies to convert DOE asbestos to a non-hazardous, radionuclide-free, stable waste. The dry, contaminated asbestos is initially heated with radiofrequency energy to remove organic volatiles. Second,the radionuclides are removed by solvent extraction coupled with ion exchange solution treatment. Third, the ABCOV method converts the asbestos to an amorphous silica suspension at low temperature (100{degrees}C). Finally the amorphous silica is solidified for disposal

Characterizing neutral and adaptive genomic differentiation in a changing climate: The most northerly freshwater fish as a model

Arctic freshwater ecosystems have been profoundly affected by climate change. Given that the Arctic charr (Salvelinus alpinus) is often the only fish species inhabiting these ecosystems, it represents a valuable model for studying the impacts of climate change on species life‐history diversity and adaptability. Using a genotyping‐by‐se‐ quencing approach, we identified 5,976 neutral single nucleotide polymorphisms and found evidence for reduced gene flow between allopatric morphs from two high Arctic lakes, Linne ́vatn (Anadromous, Normal, and Dwarf) and Ellasjøen (Littoral and Pelagic). Within each lake, the degree of genetic differentiation ranged from low (Pelagic vs. Littoral) to moderate (Anadromous and Normal vs. Dwarf). We identified 17 highly diagnostic, putatively adaptive SNPs that differentiated the allopatric morphs. Although we found no evidence for adaptive differences between morphs within Ellasjøen, we found evidence for moderate (Anadromous vs. Normal) to high genetic differentiation (Anadromous and Normal vs. Dwarf) among morphs within Linne ́vatn based on two adaptive loci. As these freshwater ecosystems become more produc‐ tive, the frequency of sympatric morphs in Ellasjøen will likely shift based on foraging opportunities, whereas the propensity to migrate may decrease in Linne ́vatn, in‐ creasing the frequency of the Normal morph. The Dwarf charr was the most geneti‐ cally distinct group. Identifying the biological basis for small body size should elucidate the potential for increased growth and subsequent interbreeding with sym‐ patric morphs. Overall, neutral and adaptive genomic differentiation between al‐ lopatric and some sympatric morphs suggests that the response of Arctic charr to climate change will be variable across freshwater ecosystems

Discovery of a single male Aedes aegypti (L.) in Merseyside, England

© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The file attached is the published (publishers PDF) version of the article

The STAFF-DWP wave instrument on the DSP equatorial spacecraft: description and first results

The STAFF-DWP wave instrument on board the equatorial spacecraft (TC1) of the Double Star Project consists of a combination of 2 instruments which are a heritage of the Cluster mission: the Spatio-Temporal Analysis of Field Fluctuations (STAFF) experiment and the Digital Wave-Processing experiment (DWP). On DSP-TC1 STAFF consists of a three-axis search coil magnetometer, used to measure magnetic fluctuations at frequencies up to 4 kHz and a waveform unit, up to 10 Hz, plus snapshots up to 180 Hz. DWP provides several onboard analysis tools: a complex FFT to fully characterise electromagnetic waves in the frequency range 10 Hz-4 kHz, a particle correlator linked to the PEACE electron experiment, and compression of the STAFF waveform data. The complementary Cluster and TC1 orbits, together with the similarity of the instruments, permits new multi-point studies. The first results show the capabilities of the experiment, with examples in the different regions of the magnetosphere-solar wind system that have been encountered by DSP-TC1 at the beginning of its operational phase. An overview of the different kinds of electromagnetic waves observed on the dayside from perigee to apogee is given, including the different whistler mode waves (hiss, chorus, lion roars) and broad-band ULF emissions. The polarisation and propagation characteristics of intense waves in the vicinity of a bow shock crossing are analysed using the dedicated PRASSADCO tool, giving results compatible with previous studies: the broad-band ULF waves consist of a superimposition of different wave modes, whereas the magnetosheath lion roars are right-handed and propagate close to the magnetic field. An example of a combined Cluster DSP-TC1 magnetopause crossing is given. This first case study shows that the ULF wave power intensity is higher at low latitude (DSP) than at high latitude (Cluster). On the nightside in the tail, a first wave event comparison - in a rather quiet time interval - is shown. It opens the doors to future studies, such as event timing during substorms, to possibly determine their onset location

West Nile virus vector Culex modestus established in southern England

Background: The risk posed to the United Kingdom by West Nile virus (WNV) has previously been considered low, due to the absence or scarcity of the main Culex sp. bridge vectors. The mosquito Culex modestus is widespread in southern Europe, where it acts as the principle bridge vector of WNV. This species was not previously thought to be present in the United Kingdom. Findings: Mosquito larval surveys carried out in 2010 identified substantial populations of Cx. modestus at two sites in marshland in southeast England. Host-seeking-adult traps placed at a third site indicate that the relative seasonal abundance of Cx. modestus peaks in early August. DNA barcoding of these specimens from the United Kingdom and material from southern France confirmed the morphological identification. Conclusions: Cx. modestus appears to be established in the North Kent Marshes, possibly as the result of a recent introduction. The addition of this species to the United Kingdom’s mosquito fauna may increase the risk posed to the United Kingdom by WNV