Toward a Structure Determination Method for Biomineral-Associated Protein Using Combined Solid- State NMR and Computational Structure Prediction

SummaryProtein-biomineral interactions are paramount to materials production in biology, including the mineral phase of hard tissue. Unfortunately, the structure of biomineral-associated proteins cannot be determined by X-ray crystallography or solution nuclear magnetic resonance (NMR). Here we report a method for determining the structure of biomineral-associated proteins. The method combines solid-state NMR (ssNMR) and ssNMR-biased computational structure prediction. In addition, the algorithm is able to identify lattice geometries most compatible with ssNMR constraints, representing a quantitative, novel method for investigating crystal-face binding specificity. We use this method to determine most of the structure of human salivary statherin interacting with the mineral phase of tooth enamel. Computation and experiment converge on an ensemble of related structures and identify preferential binding at three crystal surfaces. The work represents a significant advance toward determining structure of biomineral-adsorbed protein using experimentally biased structure prediction. This method is generally applicable to proteins that can be chemically synthesized

25 Jahre Sulfonylharnstoff-Herbizide – ein paar Gramm veränderten die Welt der chemischen Unkrautbekämpfung

Mit der Entdeckung der herbiziden Wirkung bestimmter Sulfonylharnstoff-Verbindungen durch George Levitt (1. Patent 1978 für DuPont) und der nachfolgenden Entwicklung und kommerziellen Einführung entsprechender Herbizide (erster in Deutschland erhältlicher Wirkstoff im Jahr 1985 war Metsulfuron-Methyl, GROPPER®) erfolgte ein Quantensprung in der chemischen Unkrautbekämpfung. Die im Vergleich zu damaligen kommerziellen Standards um den Faktor 100 bis 1000 drastisch verringerten Aufwandmengen, der völlig neuartige Wirkmechanismus (Hemmung des Enzyms Acetolactatsynthase, ALS), die flexiblen Einsatzmöglichkeiten vom frühen bis zum späten Nachauflauf und die günstigen Anwender- und Umweltsicherheitsprofile dieser Herbizide setzten einen neuen Standard, der bis heute nicht übertroffen wurde. Insgesamt wurden von mehreren Firmen seitdem weltweit über 30 Moleküle aus dieser Chemieklasse entwickelt und registriert, mit Einsatzmöglichkeiten in praktisch allen Ackerbaukulturen; es folgten noch weitere Verbindungs-klassen it dem gleichen Wirkungsmechanismus.Sulfonylharnstoffe werden über Blatt und Wurzel aufgenommen und akropetal und basipetal in der ganzen Pflanze verteilt. Die spezifische Hemmung der Acetolactatsynthase blockiert die Biosynthese der verzweigtkettigen Aminosäuren Valin, Leucin und Isoleucin und damit die Proteinsynthese. Die Kulturselektivität spezifischer Sulfonylharnstoffe in den verschiedenen Ackerbaukulturen beruht auf einem raschen Metabolismus des jeweiligen Wirkstoffs. Der Abbau im Boden kann über mikrobielle und/oder chemische Prozesse erfolgen, wobei die Halbwertzeiten molekül-, boden- und klimaabhängig sind. Durch vieljährige einseitige Selektion entstandene Unkrautpopulationen mit Resistenzen gegen ALS-Hemmer weisen entweder spezifische Punktmutationen am Zielenzym ALS oder einen beschleunigten Metabolismus des Wirkstoffs auf.Für eine erfolgreiche chemische Unkrautbekämpfung in der gesamten Fruchtfolge sind die Sulfonylharnstoffe im Zusammenhang mit der Verfügbarkeit anderer herbizider Wirkstoffklassen zu betrachten. Die Zukunft der bestehenden Wirkstoffe und die Aussicht auf weitere grundlegende Neuerungen im Bereich der Herbizide wird von der weiteren Entwicklung der Herbizidresistenztechnologien aus Kulturpflanze und Komplementärherbizid sowie dem Auffinden neuer Wirkungsmechanismen abhängen. Auch der zunehmende Anteil bewährter Altwirkstoffe, die preiswert verfügbar bleiben, beeinflusst über die Wirtschaftlichkeitsbetrachtung den Aufwand und Erfolg der Suche nach neuen Wirkungsmechanismen.Stichwörter: Acetolactatsynthase, ALS-Hemmer, Herbizidresistenz, Sulfonylharnstoff25 years of sulfonylurea herbicides – a few grams changed the world of chemical weed controlWith the discovery of herbicidal activity of certain sulfonylurea compounds by George Levitt (first patent awarded to DuPont in 1978) and with the subsequent development and commercialization of herbicides from this class (i.e. Metsulfuron-Methyl, GROPPER®, first registered as a product in Germany in 1985) a quantum leap in herbicide technology was achieved. The drastically reduced use rates (by a factor of 100- to 1000-fold compared with standard products of the time), the entirely new mechanism of action (inhibition of the ALS enzym), flexible application (pre- or post-emergent), and the outstanding safety to the applicator and the environment set a new standard for herbicides, which even today has not been superseded. A total of over 30 molecules have been commercialized from this class world-wide, with uses in practically all major row crops. Several additional structural subclasses with the same mode of action have followed. Sulfonylureas enter plants through foliar and soil uptake and are translocated acropetally and basipetally within the plant. The mechanism of action is through the inhibition of the acetolactate synthase enzyme, blocking the synthesis of the branched chain amino acids valine, leucine and isoleucine, and thus inhibiting protein synthesis. Selectivity is achieved through the rapid metabolism of the active substance to inactive metabolites within the crop before it can act. Sulfonylureas degrade in soils mainly through microbial action or through chemical hydrolysis; degradation rates and pathways are specific to the molecule, soil and climate. Selection of resistant individuals through continuous application of sulfonylurea herbicides over many years led to the development of resistant weed populations that possess specific point mutations in the ALS enzyme, or the ability to rapidly metabolize the active ingredient.The sulfonylureas must be compared with other important classes of herbicides as components of a sustainable weed management system within various crop rotations. The future of existing herbicide classes and the prospects for future basic advances in weed management technologies depend on the further development of technologies to counter herbicide resistance (crops and complementary herbicides), and the discovery of herbicides with novel modes of action. Keywords: Acetolactate synthase, ALS inhibitor, herbicide resistance, sulfonylure

Engineering two-mode interactions in ion traps

Published versio

Ultrathin 2 nm gold as ideal impedance-matched absorber for infrared light

Thermal detectors are a cornerstone of infrared (IR) and terahertz (THz) technology due to their broad spectral range. These detectors call for suitable broad spectral absorbers with minimalthermal mass. Often this is realized by plasmonic absorbers, which ensure a high absorptivity butonly for a narrow spectral band. Alternativly, a common approach is based on impedance-matching the sheet resistance of a thin metallic film to half the free-space impedance. Thereby, it is possible to achieve a wavelength-independent absorptivity of up to 50 %, depending on the dielectric properties of the underlying substrate. However, existing absorber films typicallyrequire a thickness of the order of tens of nanometers, such as titanium nitride (14 nm), whichcan significantly deteriorate the response of a thermal transducers. Here, we present the application of ultrathin gold (2 nm) on top of a 1.2 nm copper oxide seed layer as an effective IR absorber. An almost wavelength-independent and long-time stable absorptivity of 47(3) %, ranging from 2 $\mu$m to 20 $\mu$m, could be obtained and is further discussed. The presented gold thin-film represents analmost ideal impedance-matched IR absorber that allows a significant improvement of state-of-the-art thermal detector technology

Deorbit kit demonstration mission

In Low Earth Orbit, it is possible to use the ambient plasma and the geomagnetic field to exchange momentum with the Earth's magnetosphere without using propellant. A device that allows an efficient momentum exchange is the electrodynamic tether (EDT), a long conductor attached to the satellite. EDT technology has been demonstrated in several past missions, being the Plasma Motor Generator mission (NASA 1993) one of the most successful. Nevertheless, it is not until today that reality has imposed a strong need and a concrete use case for developing this technology. In March 2019, the European Commission project Electrodynamic Tether technology for PAssive Consumable-less deorbit Kit (E.T.PACK) started the design of a new generation EDT. After completing the design phase, the consortium manufactured and is currently testing a Deorbit Kit Demonstrator (DKD) breadboard based on EDT technology. The objective of E.T.PACK is to reach Technology Readiness Level equal to 4 by 2022. The DKD is a standalone 24-kg satellite with the objective to demonstrate the performances of the improved EDT solution and validate its ultra-compact deployment system. The DKD is composed of two modules that will separate in orbit extending a 500-m long tape-like tether. The deployed bare-Aluminium tether will capture electrons from the ambient plasma passively and the circuit will be closed with the ionospheric plasma by using an active electron emitter. E.T.PACK tether will take advantage of several novelties with respect to the mission flown in the past that will allow to optimize the system volume and mass. Once successful demonstrated in orbit, the team plans to develop a suite of EDT systems capable of deorbiting satellites between 200 and 1000 kg from an altitude up to 1200 km in a few months. The work presents the current design status of the de-orbit kit demonstrator breadboard, the simulations of the system deorbit performances and the development approach.This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No.828902 (3M€ E.T.PACK project) and No.101034874 (100K€ BMOM project). SG is supported by an Industrial Ph.D funded by Comunidad de Madrid (135K€ IND2019/TIC17198). The team has recently got 2.5M€ additional financial support from European Union (ETPACK-F project No. 101058166) for the manufacturing and qualification of the In Orbit Demonstration (IOD) by the end of 2025

Quantum interference in three-photon down-conversion

Published versio

A multicentre matched case control study of risk factors for Preeclampsia in healthy women in Pakistan

<p>Abstract</p> <p>Background</p> <p>Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality world-wide. The risk for developing preeclampsia varies depending on the underlying mechanism. Because the disorder is heterogeneous, the pathogenesis can differ in women with various risk factors. Understanding these mechanisms of disease responsible for preeclampsia as well as risk assessment is still a major challenge. The aim of this study was to determine the risk factors associated with preeclampsia, in healthy women in maternity hospitals of Karachi and Rawalpindi.</p> <p>Methods</p> <p>We conducted a hospital based matched case-control study to assess the factors associated with preeclampsia in Karachi and Rawalpindi, from January 2006 to December 2007. 131 hospital-reported cases of PE and 262 controls without history of preeclampsia were enrolled within 3 days of delivery. Cases and controls were matched on the hospital, day of delivery and parity. Potential risk factors for preeclampsia were ascertained during in-person postpartum interviews using a structured questionnaire and by medical record abstraction. Conditional logistic regression was used to estimate matched odds ratios (ORs) and 95% confidence intervals (95% CIs).</p> <p>Results</p> <p>In multivariate analysis, women having a family history of hypertension (adjusted OR 2.06, 95% CI; 1.27-3.35), gestational diabetes (adjusted OR 6.57, 95% CI; 1.94 -22.25), pre-gestational diabetes (adjusted OR 7.36, 95% CI; 1.37-33.66) and mental stress during pregnancy (adjusted OR 1.32; 95% CI; 1.19-1.46, for each 5 unit increase in Perceived stress scale score) were at increased risk of preeclampsia. However, high body mass index, maternal age, urinary tract infection, use of condoms prior to index pregnancy and sociodemographic factors were not associated with higher risk of having preeclampsia.</p> <p>Conclusions</p> <p>Development of preeclampsia was associated with gestational diabetes, pregestational diabetes, family history of hypertension and mental stress during pregnancy. These factors can be used as a screening tool for preeclampsia prediction. Identification of the above mentioned predictors would enhance the ability to diagnose and monitor women likely to develop preeclampsia before the onset of disease for timely interventions and better maternal and fetal outcomes.</p

Preparation of nonclassical states in cavities with a moving mirror

Published versio

Alzheimer's Disease: a Review of its Visual System Neuropathology. Optical Coherence Tomography-a Potential Role As a Study Tool in Vivo

Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on in-vivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.info:eu-repo/semantics/publishedVersio