The scorpion toxin BeKm-1 blocks hERG cardiac potassium channels using an indispensable arginine residue.

BeKm-1 is a peptide toxin from scorpion venom that blocks the pore of the potassium channel hERG (K11.1) in the human heart. Although individual protein structures have been resolved, the structure of the complex between hERG and BeKm-1 is unknown.

Kalium 3.0 is a comprehensive depository of natural, artificial, and labeled polypeptides acting on potassium channels.

Here, we introduce the third release of Kalium database (http://kaliumdb.org/), a manually curated comprehensive depository that accumulates data on polypeptide ligands of potassium channels. The major goal of this amplitudinous update is to summarize findings for natural polypeptide ligands of K channels, as well as data for the artificial derivatives of these substances obtained over the decades of exploration.

Methionine-isoleucine dichotomy at a key position in scorpion toxins inhibiting voltage-gated potassium channels.

Previous studies have identified some key amino acid residues in scorpion toxins blocking potassium channels. In particular, the most numerous toxins belonging to the α-KTx family and affecting voltage-gated potassium channels (K) present a conserved K-C-X-N motif in the C-terminal half of their sequence. Here, we show that the X position of this motif is almost always occupied by either methionine or isoleucine.

Apamin structure and pharmacology revisited.

Apamin is often cited as one of the few substances selectively acting on small-conductance Ca-activated potassium channels (K2). However, published pharmacological and structural data remain controversial. Here, we investigated the molecular pharmacology of apamin by two-electrode voltage-clamp in oocytes and patch-clamp in HEK293, COS7, and CHO cells expressing the studied ion channels, as well as in isolated rat brain neurons.

The Dynamics of Antimicrobial Resistance among Enterobacteriaceae Isolates in Russia: Results of the 2012-2018 INFORM and ATLAS International Program Studies.

Background: The increasing prevalence of multidrug-resistant Enterobacteriaceae limits the range of active antimicrobial agents, thus worsening clinical outcomes. The objective of this study was to identify the trends in antimicrobial resistance for Enterobacteriaceae in Russia using the databases for the International Network for Optimal Resistance Monitoring (INFORM) and Antimicrobial Testing Leadership and Surveillance (ATLAS) studies between 2012 and 2018. Methods: This subanalysis was performed for 3811 non-duplicate clinical isolates of Enterobacteriaceae to evaluate the in vitro activity of the main classes of antibiotics against relevant clinical isolates from hospitalized patients with complicated infections of different anatomical locations.

Snake Toxins Labeled by Green Fluorescent Protein or Its Synthetic Chromophore are New Probes for Nicotinic acetylcholine Receptors.

Fluorescence can be exploited to monitor intermolecular interactions in real time and at a resolution up to a single molecule. It is a method of choice to study ligand-receptor interactions. However, at least one of the interacting molecules should possess good fluorescence characteristics, which can be achieved by the introduction of a fluorescent label.

AMRmap: An Interactive Web Platform for Analysis of Antimicrobial Resistance Surveillance Data in Russia.

Surveillance of antimicrobial resistance (AMR) is crucial for identifying trends in resistance and developing strategies for prevention and treatment of infections. Globally, AMR surveillance systems differ in terms of organizational principles, comprehensiveness, accessibility, and usability of data presentation. Until recently, the data on AMR in Russia were scarcely available, especially to international community, despite the fact that the large prospective multicenter surveillance in Russia was conducted and data were accumulated for over 20 years.

Design optimization for bright electrically-driven quantum dot single-photon sources emitting in telecom O-band.

A combination of advanced light engineering concepts enables a substantial improvement in photon extraction efficiency of micro-cavity-based single-photon sources in the telecom O-band at ∼1.3 µm. We employ a broadband bottom distributed Bragg reflector (DBR) and a top DBR formed in a dielectric micropillar with an additional circular Bragg grating in the lateral plane.

Structure of MeuNaTxα-1 toxin from scorpion venom highlights the importance of the nest motif.

Old world scorpions produce an abundance of toxins called α-NaTx, which interfere with the fast inactivation of voltage-gated sodium channels. Their selectivity to channels of mammals or insects depends on a part of toxin named the specificity module. We report here the spatial structure of a major and broadly active toxin MeuNaTxα-1 from the venom of Mesobuthus eupeus.

Scorpion toxin MeuNaTxα-1 sensitizes primary nociceptors by selective modulation of voltage-gated sodium channels.

Venoms are a rich source of highly specific toxins, which allow the identification of novel therapeutic targets. We have now applied high content screening (HCS) microscopy to identify toxins that modulate pain sensitization signaling in primary sensory neurons of rat and elucidated the underlying mechanism. A set of venoms and fractions thereof were analyzed for their ability to activate type II protein kinase A (PKA-II) and extracellular signal-regulated kinases (ERK1/2).

Tuning Scorpion Toxin Selectivity: Switching From K1.1 to K1.3.

Voltage-gated potassium channels (Ks) perform vital physiological functions and are targets in different disorders ranging from ataxia and arrhythmia to autoimmune diseases. An important issue is the search for and production of selective ligands of these channels. Peptide toxins found in scorpion venom named KTx excel in both potency and selectivity with respect to some potassium channel isoforms, which may present only minute differences in their structure.

Scots pine as a promising indicator organism for biomonitoring of the polluted environment: A case study on chronically irradiated populations.

In this paper the main results of long-term (2003-2016) observations on Scots pine populations inhabiting sites affected by the Chernobyl accident are presented. Populations growing for many years under chronic radiation exposure are characterized by the enhanced mutation rates, increased genetic diversity, changes in the gene expression and in the level of genome-wide methylation, alterations in the temporal dynamics of cytogenetic abnormalities and genetic structure of populations. However, significant changes at the genetic level had no effects on enzymatic activity, morphological abnormalities, and reproductive ability of pine trees.

Kalium 2.0, a comprehensive database of polypeptide ligands of potassium channels.

Potassium channels are the most diverse group of ion channels in humans. They take vital parts in numerous physiological processes and their malfunction gives rise to a range of pathologies. In addition to small molecules, there is a wide selection of several hundred polypeptide ligands binding to potassium channels, the majority of which have been isolated from animal venoms.

K1.2 channel-specific blocker from Mesobuthus eupeus scorpion venom: Structural basis of selectivity.

Scorpion venom is an unmatched source of selective high-affinity ligands of potassium channels. There is a high demand for such compounds to identify and manipulate the activity of particular channel isoforms. The objective of this study was to obtain and characterize a specific ligand of voltage-gated potassium channel K1.

Chronic radiation exposure modifies temporal dynamics of cytogenetic but not reproductive indicators in Scots pine populations.

Over a period of 13 years (2003-2015), reproductive and cytogenetic effects are investigated in Scots pine populations growing in the Bryansk region of Russia radioactively contaminated as a result of the Chernobyl accident. In reference populations, the frequencies of cytogenetic abnormalities are shown to change with time in a cyclic manner. In chronically exposed populations, the cyclic patterns in temporal dynamics of cytogenetic abnormalities appear to be disturbed.

Labelled animal toxins as selective molecular markers of ion channels: Applications in neurobiology and beyond.

Animal toxins are traditional and indispensible molecular tools that find application in different fields of biochemistry, neurobiology and pharmacology. These compounds possess several outstanding properties such as high affinity and selectivity with respect to particular molecular targets, most importantly ion channels and neuroreceptors, and stability. In addition to using toxins per se, a wide variety of labelled modifications have been obtained including radioactive and fluorescent derivatives.

Influence of long-term chronic exposure and weather conditions on Scots pine populations.

Over a period of 8 years (2007-2014), we were evaluating seed quality and morphological abnormalities in Scots pine trees affected as a result of the Chernobyl accident. The calculated dose rates for the trees at the study sites varied from background values at the reference sites to 40 mGy/year at the most contaminated site. We investigated whether radioactive contamination and/or weather factors could decrease the reproductive capacity or increase the frequency of morphological abnormalities of needles in pine trees.

C-Terminal residues in small potassium channel blockers OdK1 and OSK3 from scorpion venom fine-tune the selectivity.

We report isolation, sequencing, and electrophysiological characterization of OSK3 (α-KTx 8.8 in Kalium and Uniprot databases), a potassium channel blocker from the scorpion Orthochirus scrobiculosus venom. Using the voltage clamp technique, OSK3 was tested on a wide panel of 11 voltage-gated potassium channels expressed in Xenopus oocytes, and was found to potently inhibit Kv1.

Fluorescent protein-scorpion toxin chimera is a convenient molecular tool for studies of potassium channels.

Ion channels play a central role in a host of physiological and pathological processes and are the second largest target for existing drugs. There is an increasing need for reliable tools to detect and visualize particular ion channels, but existing solutions suffer from a number of limitations such as high price, poor specificity, and complicated protocols. As an alternative, we produced recombinant chimeric constructs (FP-Tx) consisting of fluorescent proteins (FP) fused with potassium channel toxins from scorpion venom (Tx).

Lachesana tarabaevi, an expert in membrane-active toxins.

In the present study, we show that venom of the ant spider Lachesana tarabaevi is unique in terms of molecular composition and toxicity. Whereas venom of most spiders studied is rich in disulfide-containing neurotoxic peptides, L. tarabaevi relies on the production of linear (no disulfide bridges) cytolytic polypeptides.

Kalium: a database of potassium channel toxins from scorpion venom.

Kalium (http://kaliumdb.org/) is a manually curated database that accumulates data on potassium channel toxins purified from scorpion venom (KTx). This database is an open-access resource, and provides easy access to pages of other databases of interest, such as UniProt, PDB, NCBI Taxonomy Browser, and PubMed.

Diversity of Potassium Channel Ligands: Focus on Scorpion Toxins.

Potassium (K+) channels are a widespread superfamily of integral membrane proteins that mediate selective transport of K+ ions through the cell membrane. They have been found in all living organisms from bacteria to higher multicellular animals, including humans. Not surprisingly, K+ channels bind ligands of different nature, such as metal ions, low molecular mass compounds, venom-derived peptides, and antibodies.

[Specific Features of Scots Pine Seeds Formation in the Remote Period after the Chernobyl NPP Accident].

The results of long-term (2007-2011) observations on the quality of seed progeny in Scots pine populations inhabiting the sites within the Bryansk region contaminated as a result of the Chernobyl NPP accident are presented. Formed under the chronic exposure seeds are characterized by a high interannual variability, which is largely determined by weather conditions.

Quantum dot semiconductor disk laser at 1.3 μm.

We present a semiconductor disk laser (SDL) emitting at the wavelength of 1.3 μm. The active region of the SDL comprises InAs quantum dots (QDs) that are embedded into InGaAs quantum wells (QWs).