A new solid-phase system for immunoassays

The development of a new solid-phase separation system based on silane polymers is described. A T3 radioimmunoassay (RIA) was optimized using coated tubes with polymer coatings containing hydrophilic surface aldehyde groups for antibody coupling and a T4 RIA developed on the basis of surface anilino group containing particles using a suspension method. Both RIAs offer very good performances and show the variable usability of the new separation system

Millisecond cryo-trapping by the spitrobot crystal plunger simplifies time-resolved crystallography

We introduce the spitrobot, a protein crystal plunger, enabling reaction quenching via cryo-trapping with millisecond time-resolution. Canonical micromesh loops are mounted on an electropneumatic piston, reactions are initiated via the liquid application method (LAMA), and finally intermediate states are cryo-trapped in liquid nitrogen. We demonstrate binding of several ligands in microcrystals of three enzymes, and trapping of reaction intermediates and conformational changes in macroscopic crystals of tryptophan synthase

A Glucose Fuel Cell for Implantable Brain–Machine Interfaces

We have developed an implantable fuel cell that generates power through glucose oxidation, producing steady-state power and up to peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain–machine interfaces can thus potentially benefit from having their implanted units powered or recharged by glucose fuel cells

Structural basis for the photoconversion of a phytochrome to the activated far-red light-absorbing form

Phytochromes are a collection of bilin-containing photoreceptors that regulate numerous photoresponses in plants and microorganisms through their ability to photointerconvert between a red light-absorbing, ground state Pr and a far-red light-absorbing, photoactivated state Pfr1,2. While the structures of several phytochromes as Pr have been determined3-7, little is known about the structure of Pfr and how it initiates signaling. Here, we describe the three-dimensional solution structure of the bilin-binding domain as Pfr using the cyanobacterial phytochrome from Synechococcus OSB’. Contrary to predictions, light-induced rotation of the A but not the D pyrrole ring is the primary motion of the chromophore during photoconversion. Subsequent rearrangements within the protein then affect intra- and interdomain contact sites within the phytochrome dimer. From our models, we propose that phytochromes act by propagating reversible light-driven conformational changes in the bilin to altered contacts between the adjacent output domains, which in most phytochromes direct differential phosphotransfer

A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016-2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn's disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson's disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions

The Congolobe project, a multidisciplinary study of Congo deep-sea fan lobe complex: Overview of methods, strategies, observations and sampling

The presently active region of the Congo deep-sea fan (around 330,000 km(2)), called the terminal lobes or lobe complex, covers an area of 2500 km(2) at 4700-5100 m water depth and 750-800 km offshore. It is a unique sedimentary area in the world ocean fed by a submarine canyon and a channel-levee system which presently deliver large amounts of organic carbon originating from the Congo River by turbidity currents. This particularity is due to the deep incision of the shelf by the Congo canyon, up to 30 km into the estuary, which funnels the Congo River sediments into the deep-sea. The connection between the river and the canyon is unique for major world rivers. In 2011, two cruises (WACS leg 2 and Congolobe) were conducted to simultaneously investigate the geology, organic and inorganic geochemistry, and micro- and macro-biology of the terminal lobes of the Congo deep-sea fan. Using this multidisciplinary approach, the morpho-sedimentary features of the lobes were characterized along with the origin and reactivity of organic matter, the recycling and burial of biogenic compounds, the diversity and function of bacterial and archaeal communities within the sediment, and the biodiversity and functioning of the faunal assemblages on the seafloor. Six different sites were selected for this study: Four distributed along the active channel from the lobe complex entrance to the outer rim of the sediment deposition zone, and two positioned cross-axis and at increasing distance from the active channel, thus providing a gradient in turbidite particle delivery and sediment age. This paper aims to provide the general context of this multidisciplinary study. It describes the general features of the site and the overall sampling strategy and provides the initial habitat observations to guide the other in-depth investigations presented in this special issue. Detailed bathymetry of each sampling site using 0.1-1 m resolution multibeam obtained with a remotely operated vehicle (ROV) shows progressive widening and smoothing of the channel-levees with increasing depth and reveals a complex morphology with channel bifurcations, erosional features and massive deposits. Dense ecosystems surveyed in the study area gather high density clusters of two large-sized species of symbiotic Vesicomyidae bivalves and microbial mats. These assemblages, which are rarely observed in sedimentary zones, resemble those based on chemosynthesis at cold-seep sites, such as the active pockmarks encountered along the Congo margin, and share with these sites the dominant vesicomyid species Christineconcha regab. Sedimentation rates estimated in the lobe complex range between 0.5 and 10 cm yr(-1), which is 2-3 orders of magnitude higher than values generally encountered at abyssal depths. The bathymetry, faunal assemblages and sedimentation rates make the Congo lobe complex a highly peculiar deep-sea habitat driven by high inputs of terrigenous material delivered by the Congo channel-levee system. (c) 2016 Elsevier Ltd. All rights reserved.ZAIANGOANR Congolobe (ANR Blanc SIMI5-6) [11 BS56 030]IFREMERCEA through LSCEU.S. National Science Foundation [OCE-0831156]info:eu-repo/semantics/acceptedVersio