Diketopiperazine/piperidine alkaloid as a potential broad-spectrum coronaviral entry inhibitor identified by supercomputer-based virtual screening from a large natural product-based library.

The COVID-19 pandemic has underscored the urgent need for antiviral agents capable of targeting a broad range of coronaviruses, including emerging variants of SARS-CoV-2. While vaccines have been pivotal, the search for drugs that can prevent viral entry into host cells remains crucial, especially against evolving viral forms and other coronaviruses. In this study, we investigated natural products as a source of antiviral agents, focusing on their potential to block the spike protein's receptor-binding domain (RBD).

Coupling of single nanodiamonds hosting SiV color centers to plasmonic double bowtie microantennas.

Color centers are promising single-photon emitters owing to their operation at room temperature and high photostability. In particular, using nanodiamonds as a host material is of interest for sensing and metrology. Furthermore, being a solid-state system allows for incorporation to photonic systems to tune both the emission intensity and photoluminescence spectrum and therefore adapt the individual color center to desired properties.

Characterization of cell membrane fragments containing muscle type nAChR from Tetronarce californica after preparation using high pressure homogenization.

The nicotinic acetylcholine receptor (nAChR) is a pentameric ligand-gated ion channel (pLGIC) commonly used as a model for receptors belonging to the Cys-loop superfamily. Members of pLGICs are standardly used in numerous toxicological investigations e.g.

Coupling of single nanodiamonds hosting SiV color centers to plasmonic double bowtie microantennas.

Color centers are promising single-photon emitters owing to their operation at room temperature and high photostability. In particular, using nanodiamonds as a host material is of interest for sensing and metrology. Furthermore, being a solid-state system allows for incorporation to photonic systems to tune both the emission intensity and photoluminescence spectrum and therefore adapt the individual color center to desired properties.

Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time-Resolved Limited Proteolysis Mass Spectrometry.

Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer-protein interaction. We deployed limited proteolysis mass spectrometry (LiP-MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon-α2a (IFN). Target conjugates were digested with the specific protease trypsin and a "heavy" N-IFN wild type (IFN-WT) for time-resolved quantification of the cleavage dynamics.

Silanediol-Bay-Bridge Rigidified Axially Chiral Perylene Bisimide.

Chiral organic molecules with a complementing π-structure are highly desired to obtain materials with good semiconducting properties and pronounced chirality effects in the visible region. Herein, we introduce a novel design strategy to achieve an axially chiral and rigid perylene bisimide (PBI) dye by attaching the chirality-inducing 2,2'-biphenoxy moiety at one side of the bay area and the rigidity-inducing di--butylsilanediol bridge on the other side. This yielded a new bay-functionalized PBI derivative carrying the combination of a highly rigid and, simultaneously, an axially chiral perylene core.

Visible-light-induced CO-releasing properties and cytotoxicity of a Ru(II) carbonyl complex containing 2-(pyridin-2-yl)-quinoxaline.

The photo-induced CO-releasing properties of the dark-stable complex [RuCl(CO)L] (L = 2-(pyridin-2-yl)quinoxaline) were investigated under 468 nm light exposure in the presence and absence of biomolecules such as histidine, calf thymus DNA and hen egg white lysozyme. The CO release kinetics were consistent regardless of the presence of these biomolecules, suggesting that they did not influence the CO release mechanism. The quinoxaline ligand demonstrated exceptional cytotoxicity against human acute monocytic leukemia cells (THP-1), with evidence of potential DNA damage ascertained by comet assay, while it remained non-toxic to normal kidney epithelial cells derived from African green monkey (Vero) cell lines.

TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.

For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.

Motor Control on the Move - from Insights in Insects to General Mechanisms.

This review discusses how the nervous system controls the complex body movements keeping animals up and running. In particular, we revisit how research in insects has shed light onto motor control principles that govern movements across the animal kingdom. Starting with the organization and evolution of the insect nervous system, we discuss insights into the neuronal control of behaviors varying in complexity, including escape, flight, crawling, walking, grooming, and courtship.

Phenotypic screens identify SCAF1 as critical activator of RNAPII elongation and global transcription.

Transcripts produced by RNA polymerase II (RNAPII) are fundamental for cellular responses to environmental changes. It is therefore no surprise that there exist multiple avenues for the regulation of this process. To explore the regulation mediated by RNAPII-interacting proteins, we used a small interfering RNA (siRNA)-based screen to systematically evaluate their influence on RNA synthesis.

Quantification of social motility indicates different colony growth phases.

colonies of the flagellated parasite exhibit characteristic fingering instability patterns. To enable data-driven and data-validated mechanistic modelling of these complex growth processes, it is crucial to first establish appropriate quantitative metrics beyond qualitative image comparisons. We present a quantification approach based on two scale-free metrics designed to characterize the shape of two-dimensional colonies.

The Shrinking Fermi Liquid Scenario for Cuprates Under the Scrutiny of Optical Conductivity Measurements.

In a recent paper [B. Michon et al., Nat.

Mixture of neonicotinoid and fungicide affects foraging activity of honeybees.

The use of plant protection products (PPPs) is a major factor contributing to global insect decline. We here use the honeybee (Apis mellifera) as a model to study combined effects of the last neonicotinoid in the EU (acetamiprid) and different fungicides on live-long foraging flights using radio frequency identification. The mixture of the sterol-biosynthesis-inhibiting fungicide difenoconazole and the insecticide acetamiprid significantly reduced the number of foraging trips per day compared to the control and each PPP alone, while a mixture of the insecticide with the non-sterol-biosynthesis inhibiting fungicide boscalid/dimoxystrobin did not affect behaviour.

Sept10 and sept12 are expressed in specific proliferating cells in zebrafish brain.

Septins are a group of cytoskeletal GTP binding proteins which are involved in different cellular processes, like cell division, exocytosis and axon growth. Their function, especially in the nervous system, is not clear. In zebrafish 16 different septins are described and for some of them the expression in the brain is described.

Clonal T cell populations scarcely impair patients with rheumatic diseases: a prospective long-term follow up study.

Background: Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations.

Reversible formation of tetraphenylpentalene, a room temperature stable antiaromatic hydrocarbon.

1,3,4,6-Tetraphenylpentalene (PhPn) has been synthesised by chemical oxidation of the corresponding pentalenide complex Mg[PhPn] with iodine. PhPn is a rare example of a room-temperature stable hydrocarbon that is antiaromatic by Hückel's rule and has been fully characterised by NMR and UV-vis spectroscopy, mass spectrometry as well as single-crystal X-ray diffraction. Quantum chemical studies including nucleus-independent chemical shift (NICS) and anisotropy of the induced current density (ACID) calculations showed the existence of an 8π antiaromatic core decorated with four independent 6π aromatic substituents.

Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress.

Many eIF4F and poly(A)-binding protein (PABP) paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types/developmental stages. Each eIF4F complex has its own proteins, messenger RNAs (mRNAs) and, consequently, a distinct function.

Intraspecific genetic diversity with unrestricted gene flow in the domoic acid-producing diatom Nitzschia navis-varingica (Bacillariophyceae) from the Western Pacific.

The benthic pennate diatom Nitzschia navis-varingica, known for producing domoic acid (DA) and its isomers, is widely distributed in the Western Pacific (WP) region. To investigate the genetic differentiation and gene flow patterns among the populations in the WP, the genetic diversity of 354 strains of N. navis-varingica was analysed using two nuclear-encoded rDNA loci: the large subunit rDNA (LSU rDNA) and the internal transcribed spacer 2 (ITS2).

Characterization of the chemical profiles and biological activities of Thesium bertramii Azn. Extracts using a combination of in vitro, in silico, and network pharmacology methods.

The genus Thesium, family Santalaceae, comprises about 350 species, and, although many of them are used as functional food and in traditional medicine, there are limited studies evaluating their pharmacological potential. The present study was designed to evaluate the chemical profile, antioxidant, and enzyme inhibition potential of aerial parts and roots of T. bertramii Azn.

Emission-Tunable B←N Lewis Pair-Functionalized Naphthalenes.

Herein, we simultaneously synthesized three different double B←N Lewis pair-functionalized naphthalenes including the asymmetric BNNY and BNNO and the mirror-symmetric BNNR, via a one-pot method. The annulation modes of the B←N Lewis pairs and the substituents on the boron atoms efficiently tune the molecular frontier orbitals and emission colors. α-Position fusion leads to a significant enhancement of the HOMO energy level and a decrease in the HOMO-LUMO gap, while the electron-withdrawing groups attached to the boron atom make the LUMO energy level more stable.

Regioregular Poly(p-phenylene iminoborane): A Strictly Alternating BN-Isostere of Poly(p-phenylene vinylene) with Stimuli-Responsive Behavior.

Incorporation of BN units into π-conjugated organic compounds, as substitutes for specific CC couples, often leads to new hybrid materials with modified physical and chemical properties. Poly(p-phenylene iminoborane)s are derived from well-known poly(p-phenylene vinylene) (PPV) by replacement of the vinylene groups by B=N linking units. Herein, an unprecedented poly(p-phenylene iminoborane) is presented that features a strictly alternating sequence of BN units along the main chain.

Modifying the Glycocalyx of Melanoma Cells via Metabolic Glycoengineering Using -Acetyl-d-glucosamine Analogues.

Tumor cells are decorated with aberrant glycan structures on cell surfaces. It is well known that the glycocalyx serves as a main cellular regulator, although its role in cancer is still not completely understood. Over recent decades, several non-natural monosaccharides carrying clickable groups have been introduced in melanoma cells.