Crimean-Congo haemorrhagic fever virus in ticks, domestic, and wild animals.

Crimean-Congo haemorrhagic fever virus (CCHFV) poses a significant public health threat due to its potential for causing severe disease in humans and its wide geographic distribution. The virus, primarily transmitted by ticks, is prevalent across Africa, Asia, Europe, and the Middle East. Understanding the virus's spread among tick populations is crucial for assessing its transmission dynamics.

Protamine 2 deficiency results in Septin 12 abnormalities.

There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associated with sperm motility. Septin 12 has several isoforms, and we show, that in the sperm, the short one (Mw 36 kDa) is mis-localized, while two long isoforms (Mw 40 and 41 kDa) are unexpectedly lost in sperm chromatin-bound protein fractions.

Plasmodium proteases and their role in development of Malaria vaccines.

Malaria remains a major health hazard for humans, despite the availability of efficacious antimalarial drugs and other interventions. Given that the disease is often deadly for children under 5 years and pregnant women living in malaria-endemic areas, an efficacious vaccine to prevent transmission and clinical disease would be ideal. Plasmodium, the causative agent of malaria, uses proteases and protease inhibitors to control and process to invade host, modulate host immunity, and for pathogenesis.

Proteases and protease inhibitors in saliva of hard ticks: Biological role and pharmacological potential.

Hard ticks (family Ixodidae) are significant vectors of pathogens affecting humans and animals. This review explores the composition of tick saliva, focusing on proteases and protease inhibitors, their biological roles, and their potential in vaccines and therapies. Tick saliva contains various proteases, mostly metalloproteases, serpins, cystatins, and Kunitz-type inhibitors, which modulate host hemostatic, immune, and wound healing responses to facilitate blood feeding and pathogen transmission.

Serological Screening of SARS-CoV-2 Infection in Several Mammalian Species in Wilhelma Zoo, Stuttgart, Germany.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects both humans and a wide range of mammalian species globally. Between July 2022 and January 2023, fifteen blood samples were collected from twelve different animal species during veterinary examinations, as well as for health control at Wilhelma Zoo, Germany. These samples were later analyzed for the presence of SARS-CoV-2 antibodies.

Outcomes of the EMDataResource cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution.

Effect of substituents at the C3´, C3´N, C10 and C2-meta-benzoate positions of taxane derivatives on their activity against resistant cancer cells.

We tested the effect of substituents at the (1) C3´, C3´N, (2) C10, and (3) C2-meta-benzoate positions of taxane derivatives on their activity against sensitive versus counterpart paclitaxel-resistant breast (MCF-7) and ovarian (SK-OV-3) cancer cells. We found that (1) non-aromatic groups at both C3´ and C3´N positions, when compared with phenyl groups at the same positions of a taxane derivative, significantly reduced the resistance of ABCB1 expressing MCF-7/PacR and SK-OV-3/PacR cancer cells. This is, at least in the case of the SB-T-1216 series, accompanied by an ineffective decrease of intracellular levels in MCF-7/PacR cells.

Protamine 2 Deficiency Results In Septin 12 Abnormalities.

There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associated with sperm motility. Septin 12 has several isoforms, and we show, that in the sperm, the short one (Mw 36 kDa) is mislocalized, while two long isoforms (Mw 40 and 41 kDa) are unexpectedly lost in sperm chromatin-bound protein fractions.

A First Look at the Relationship Between Large Herbivore-Induced Landscape Modifications and Tick Abundance in Rewilding Sites.

While the influence of landscape and microclimatic conditions on tick populations is well-documented, there remains a gap in more specific data regarding their relationship to rewilding efforts with large herbivore activity. This pilot study, spanning from 2019 to 2021, explores the effects of naturalistic grazing by large semi-wild ungulates on tick abundance in the Milovice Reserve, Czechia. Tick collection was observed using flagging techniques at two distinct sites of rewilding area: one grazed, actively utilized by animals involved in the rewilding project, and one ungrazed, left fallow in neighboring areas utilized only by wild animals.

Small protein blockers of human IL-6 receptor alpha inhibit proliferation and migration of cancer cells.

Background: Interleukin-6 (IL-6) is a multifunctional cytokine that controls the immune response, and its role has been described in the development of autoimmune diseases. Signaling via its cognate IL-6 receptor (IL-6R) complex is critical in tumor progression and, therefore, IL-6R represents an important therapeutic target.

Methods: An albumin-binding domain-derived highly complex combinatorial library was used to select IL-6R alpha (IL-6Rα)-targeted small protein binders using ribosome display.

Engineering PD-1-targeted small protein variants for in vitro diagnostics and in vivo PET imaging.

Background: Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the sensitivity to treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated with the increase of tumor infiltrating PD-1 lymphocytes. Due to solid tumor heterogeneity of PD-1 populations, novel low molecular weight anti-PD-1 high-affinity diagnostic probes can increase the reliability of expression profiling of PD-1 tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies and in vivo mapping efficiency using immune-PET imaging.

Genetic background of adaptation of Crimean-Congo haemorrhagic fever virus to the different tick hosts.

Crimean-Congo haemorrhagic fever orthonairovirus (CCHFV) is a negative-sense, single-stranded RNA virus with a segmented genome and the causative agent of a severe Crimean-Congo haemorrhagic fever (CCHF) disease. The virus is transmitted mainly by tick species in Hyalomma genus but other ticks such as representatives of genera Dermacentor and Rhipicephalus may also be involved in virus life cycle. To improve our understanding of CCHFV adaptation to its tick species, we compared nucleotide composition and codon usage patterns among the all CCHFV strains i) which sequences and other metadata as locality of collection and date of isolation are available in GenBank and ii) which were isolated from in-field collected tick species.

Outcomes of the EMDataResource Cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein/nucleic-acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution.

Isotopic Depletion Increases the Spatial Resolution of FPOP Top-Down Mass Spectrometry Analysis.

Protein radical labeling, like fast photochemical oxidation of proteins (FPOP), coupled to a top-down mass spectrometry (MS) analysis offers an alternative analytical method for probing protein structure or protein interaction with other biomolecules, for instance, proteins and DNA. However, with the increasing mass of studied analytes, the MS/MS spectra become complex and exhibit a low signal-to-noise ratio. Nevertheless, these difficulties may be overcome by protein isotope depletion.

Structural, Biochemical, and Computational Characterization of Sulfamides as Bimetallic Peptidase Inhibitors.

The sulfonamide function is used extensively as a general building block in various inhibitory scaffolds and, more specifically, as a zinc-binding group (ZBG) of metalloenzyme inhibitors. Here, we provide biochemical, structural, and computational characterization of a metallopeptidase in complex with inhibitors, where the mono- and bisubstituted sulfamide functions are designed to directly engage zinc ions of a bimetallic enzyme site. Structural data showed that while monosubstituted sulfamides coordinate active-site zinc ions via the free negatively charged amino group in a canonical manner, their bisubstituted counterparts adopt an atypical binding pattern divergent from expected positioning of corresponding tetrahedral reaction intermediates.

Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.

N-methyl-D-aspartate receptors (NMDARs) play a critical role in normal brain function, and variants in genes encoding NMDAR subunits have been described in individuals with various neuropsychiatric disorders. We have used whole-cell patch-clamp electrophysiology, fluorescence microscopy and in-silico modeling to explore the functional consequences of disease-associated nonsense and frame-shift variants resulting in the truncation of GluN2A or GluN2B C-terminal domain (CTD). This study characterizes variant NMDARs and shows their reduced surface expression and synaptic localization, altered agonist affinity, increased desensitization, and reduced probability of channel opening.

Are kuravirus capsid diameters quantized? The first all-atom genome tracing method for double-stranded DNA viruses.

The revolution in cryo-electron microscopy has resulted in unprecedented power to resolve large macromolecular complexes including viruses. Many methods exist to explain density corresponding to proteins and thus entire protein capsids have been solved at the all-atom level. However methods for nucleic acids lag behind, and no all-atom viral double-stranded DNA genomes have been published at all.

Mapping the potential distribution of the principal vector of Crimean-Congo haemorrhagic fever virus Hyalomma marginatum in the Old World.

Crimean-Congo haemorrhagic fever (CCHF) is the most widely distributed tick-borne viral disease in humans and is caused by the Crimean-Congo haemorrhagic fever virus (CCHFV). The virus has a broader distribution, expanding from western China and South Asia to the Middle East, southeast Europe, and Africa. The historical known distribution of the CCHFV vector Hyalomma marginatum in Europe includes most of the Mediterranean and the Balkan countries, Ukraine, and southern Russia.

Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an tick bite.

Ticks are hematophagous arthropods that use a complex mixture of salivary proteins to evade host defenses while taking a blood meal. Little is known about the immunological and physiological consequences of tick feeding on humans. Here, we performed the first bulk and single-nucleus RNA sequencing (snRNA-seq) of skin and blood of four persons presenting with naturally acquired, attached ticks.

When will RNA get its AlphaFold moment?

The protein structure prediction problem has been solved for many types of proteins by AlphaFold. Recently, there has been considerable excitement to build off the success of AlphaFold and predict the 3D structures of RNAs. RNA prediction methods use a variety of techniques, from physics-based to machine learning approaches.

First Detection of SARS-CoV-2 in White Rhinoceros during a Small-Scale Coronavirus Surveillance in the Bandia Reserve, Senegal.

The SARS-CoV-2 pandemic has heightened interest in the monitoring and surveillance of coronaviruses in wildlife. Testing for the virus in animals can provide valuable insights into viral reservoirs, transmission, and pathogenesis. In this study, we present the results of the molecular surveillance project focused on coronaviruses in Senegalese wildlife.

Assessment and strategy development for SARS-CoV-2 screening in wildlife: A review.

Coronaviruses (members of the family) are prominent in veterinary medicine, with several known infectious agents commonly reported. In contrast, human medicine has disregarded coronaviruses for an extended period. Within the past two decades, coronaviruses have caused three major outbreaks.

Overview of game meat utilisation challenges and opportunities: A European perspective.

Re-wilding and similar initiatives have resulted in an increase in wildlife suitable for human consumption in Europe. However, game meat production and consumption present several challenges, including infectious diseases which pose risks to livestock, processers, and consumers. This review provides insights into the infectious diseases and toxic contaminants associated with game meat.