A simple method for developing lysine targeted covalent protein reagents

Peptide-based covalent probes can target shallow protein surfaces not typically addressable using small molecules, yet there is a need for versatile approaches to convert native peptide sequences into covalent binders that can target a broad range of residues. Here we report protein-based thio-methacrylate esters—electrophiles that can be installed easily on unprotected peptides and proteins via cysteine side chains, and react efficiently and selectively with cysteine and lysine side chains on the target. Methacrylate phosphopeptides derived from 14-3-3-binding proteins irreversibly label 14-3-3σ via either lysine or cysteine residues, depending on the position of the electrophile. Methacrylate peptides targeting a conserved lysine residue exhibit pan-isoform binding of 14-3-3 proteins both in lysates and in extracellular media. Finally, we apply this approach to develop protein-based covalent binders. A methacrylate-modified variant of the colicin E9 immunity protein irreversibly binds to the E9 DNAse, resulting in significantly higher thermal stability relative to the non-covalent complex. Our approach offers a simple and versatile route to convert peptides and proteins into potent covalent binders.</p

Организация электроснабжения электрохимической защиты магистральных трубопроводов

В процессе эксплуатации магистральные газопроводы (МГ), как и большинство других металлических подземных коммуникаций, подвергаются воздействию процессов коррозии. Интенсивность этих процессов, а, следовательно, и состояние МГ зависит от целого ряда факторов, к числу которых следует отнести: коррозионную активность и характеристики грунтов в местах прокладки газопровода, глубину залегания участков газопровода, пересечениями с ЛЭП высокого напряжения или с электрифицированной железной дорогой – источниками блуждающих токов, качеством изоляционного покрытия, наличием и эффективностью настройки средств электрохимической защитыIn the process of exploitation of magistral gas pipelines (MG), like most other metal pose of communication, are exposed to corrosion processes. The intensity of these processes, and, consequently, the condition of the person MG depends on a number of factors, among which include: corrosiveness and the characteristics of the grunts in the field strip, the gazebo, the depth of the selenium sites gazebo leading from Lap high voltage electrician or from the sale of honey for the presence of wandering well, the quality of the insulation coating, lithium and effective tuning of electrochemical protectio

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America

BATScan: A radar classification tool reveals large‐scale bat migration patterns

Abstract Bat movement and behaviour are still mostly understudied over large scales. High‐altitude, nocturnal activity makes visual identification of bats from the ground virtually impossible, dramatically hindering our ability to study their movement ecology. Despite the wide use of radar in aeroecology, its application to study specific taxa is limited due to incomplete target classification abilities. BATScan is a bat classifier for vertical‐looking radar data, which enables identifying bats and characterizing their unique aeroecology. We constructed the classifier using data from 10 radar deployments, covering a wide range of habitats on a central bird migration flyway over a 7‐year period, comprising ~18 million observations. We analysed animal migration above the Hula Valley, home to over 30 species of bats spanning a range of 5–150 g in size and exhibiting a variety of ecological characteristics. We distinguished bat‐labelled radar echoes for training according to phenology, morphology and movement ecology of bats, birds and insects. Several non‐bat datasets were constructed and joined to train classifiers under increasing levels of difficulty. Class imbalance in the resulting training data was handled using a generative adversarial network for up‐sampling the much smaller bat dataset. The resulting classification tool reached a high level of accuracy and precision, and was further scrutinized with an extensive set of ecological validations. Bats perform seasonal migrations over long distances, but little is known about the spatial and temporal characteristics of this movement, and the ability to study it at a large scale has so far been limited. We present the Israeli BATScan dataset, containing over 60,000 bat observations spanning the entire country and representing multiple habitats. Using this data, we produce an unprecedented large scale, highly detailed documentation of the yearly movements of bats on a major migration flyway, and distinguish this pattern from bird migration over space and time. So far, radar aeroecology dealt primarily with birds, increasingly with insects, and only rarely with bats. We present BATScan, a classification tool that can incorporate bats into the framework of radar aeroecology to finally enable a comprehensive description of animal aeroecology

Studying the Physical and Chemical Properties of Polydimethylsiloxane Matrix Reinforced by Nanostructured TiO₂ Supported on Mesoporous Silica

In this study, a reactive adsorbent filler was integrated into a polymeric matrix as a novel reactive protective barrier without undermining its mechanical, thermal, and chemical properties. For this purpose, newly synthesized TiO2/MCM/polydimethylsiloxane (PDMS) composites were prepared, and their various properties were thoroughly studied. The filler, TiO2/MCM, is based on a (45 wt%) TiO2 nanoparticle catalyst inside the pores of ordered mesoporous silica, MCM-41, which combines a high adsorption capacity and catalytic capability. This study shows that the incorporation of TiO2/MCM significantly enhances the composite’s Young’s modulus in terms of tensile strength, as an optimal measurement of 1.6 MPa was obtained, compared with that of 0.8 MPa of pristine PDMS. The composites also showed a higher thermal stability, a reduction in the coefficient of thermal expansion (from 290 to 110 ppm/°C), a 25% reduction in the change in the normalized specific heat capacity, and an increase in the thermal degradation temperatures. The chemical stability in organic environments was improved, as toluene swelling decreased by 40% and the contact angle increased by ~15°. The enhanced properties of the novel synthesized TiO2/MCM/PDMS composite can be used in various applications where a high adsorption capacity and catalytic/photocatalytic activity are required, such as in protective equipment, microfluidic applications, and chemical sensor devices

Phosphate Additives for Aging Inhibition of Impregnated Activated Carbon against Hazardous Gases

Impregnated activated carbons (IACs) used in air filtration gradually lose their efficacy for the chemisorption of noxious gases when exposed to humidity due to impregnated metal deactivation. In order to stabilize IACs against aging, and to prolong the filters’ shelf life, inorganic phosphate compounds (phosphoric acid and its three salts, NaHPO4, Na2HPO4, and Na3PO4) were used as anti-aging additives for two different chromium-free IACs impregnated with copper, zinc, molybdenum, and triethylenediamine (TEDA). Phosphoric acid, monosodium, and disodium phosphate were found to be very efficient in inhibiting the aging of IACs over long periods against cyanogen chloride (the test agent) chemisorption, with the latter being the most efficient. However, the efficiency of phosphate as an anti-aging additive was not well correlated with its ability to inhibit the migration of metal impregnants, especially copper, from the interior to the external surface of carbon granules. Unlike organic additives, the inorganic phosphate additives did not decrease the surface area of the IAC or its physical adsorption capacity for toluene. Using a phosphate additive in IAC used in collective protection and personal filters can improve the safety of the user and the environment and dramatically reduce the need to replace these filters after exposure to humid environments. This has safety, economic, logistical, and environmental advantages

Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced Arthritic Mice

Rheumatoid arthritis (RA) is characterized by chronic autoinflammation of the joints, with a prevalence of about 1% in Western populations. Evidence in recent years has linked RA to changes in the gut microbiota (dysbiosis). Interestingly, helminths have been shown to have therapeutic activity in RA. Specifically, a glycoprotein containing phosphorylcholine (PC) extracted from helminths was found to have immunomodulatory activity. We have previously developed a novel chimeric compound composed of tuftsin-PC (TPC) that attenuates the joint destruction in mice with collagen-induced arthritis (CIA). Here, we address the interrelationship between TPC immunomodulatory activity and the gut microbiota in CIA mice. Preventive therapy with TPC in mice with arthritis maintained a physiological arthritis score as well as a steady gut microbial environment, similar to that of healthy controls, in contrast to CIA mice with severe disease. The microbial composition differed significantly between healthy and phosphate-buffered saline-treated CIA mice, enabling classifying test samples by machine learning based on levels of a small number of bacterial species. Using these bacterial biomarkers, all TPC-treated CIA mice were classified as healthy. Thus, we describe a clear correlation between TPC treatment, healthy gut microbial communities, and prevention of arthritis. This is the first study to demonstrate the immunomodulatory effect of helminth derivatives in autoimmune diseases and the link to gut microbiota

Hydrothermal Degradation of Chemical Warfare Agents on Activated Carbon: Rapid Chemical-Free Decontamination

Hydrothermal treatment of activated carbon contaminated with adsorbed HD, VX, or sarin at temperatures of 90–120 °C decomposes >95% of the adsorbed chemical warfare agents within a period of 0.5–4 h, in an environmentally friendly route that is free of corrosive chemicals and ends in nontoxic products