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Correction for Armstrong et al., Genetic differentiation and precolonial Indigenous cultivation of hazelnut ( <i>Corylus cornuta</i> , Betulaceae) in western North America
Correction for Yun et al., GPCR targeting of E3 ubiquitin ligase MDM2 by inactive β-arrestin
Correction for Zhou et al., A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms
Correction for Huo et al., Hierarchical behavior control by a single class of interneurons
Nocturnal camouflage through background matching against moonlight
Camouflage is often considered a daytime phenomenon based on light and shade. Nocturnal camouflage can also occur, but its mechanistic basis remains unclear. Here, we analyze the conditions for background matching (BM) of avian predators against the night sky. Such concealment is achieved when the contrast between the predator and the sky is smaller than the contrast detection threshold of prey. This condition cannot be fulfilled under isotropic skies, as in fully overcast or moonless nights. However, on clear moonlit nights, the isotropy of the sky radiance is broken due to the presence of the Moon, and the conditions for BM can be met for a wide range of sky directions. This effect is mainly dependent on the altitude of the Moon above the horizon, rather than on Moon phase. We have modeled the feasibility of concealment through BM of a typically white barn owl ( Tyto alba ) when hunting rodents, based on its contrast against the moonlit sky. We considered the radiometric quantities of the sky, the ground, and the bird’s undersides. Our results show that a barn owl with highly reflecting underparts may approach a rodent from broad regions of the moonlit sky while keeping itself below the contrast detection threshold of the mouse M-cones and rods. S-cones, in turn, remain below their excitation threshold for most of the lunar cycle. Our results demonstrate that the white color of barn owls serves as camouflage tailored to the moonlit sky background, providing a mechanistic basis for understanding nocturnal camouflage.
Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma
AbstractExtensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing stable phenotypic changes in GBM cells. Furthermore, Endocan confers radioprotection on GBM cells in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue GBM recurrence and highlight the importance of vascular-tumor interactions for GBM development.
In situ training of an in-sensor artificial neural network based on ferroelectric photosensors
Recombinant venom proteins in insect seminal fluid reduce female lifespan
QRFP43 modulates the activity of the hypothalamic-pituitary-thyroid axis in female sheep
AbstractSince the early discovery of QRFP43, intensive research has been primarily focused on its role in the modulation of food intake. As is widely recognised, the regulation of the body’s energy status is a highly complex process involving numerous systems, hormones and neurotransmitters. Among the most important regulators of energy status, alongside the satiety and hunger centre located in the hypothalamus, is the HPT axis, which directly and indirectly affects the regulation of metabolism in all cells of the body. Therefore, it seems highly important to conduct studies aimed at elucidating how QRFP43 may impact the secretory activity of the HPT axis. The objective of this work was to investigate the role of QRFP43 in modulating HPT axis activity in sheep. The study examined mRNA and peptide expression of TRH and TSH in the hypothalamus and pituitary, as well as plasma concentrations of TSH, free T4 (FT4) and free T3 (FT3). Moreover, the relationship between QRFP34 and mRNA expression of the Dio1, Dio2, and Dio3 genes was explored in selected tissues of the HPT axis. The animals (n = 48) were randomly divided into three experimental groups: a control group receiving an ICV infusion of Ringer-Locke solution, and two experimental groups receiving ICV infusions of QRFP43 at doses of 10 and 50 µg per day. Four 50-minute ICV infusions were administered to all sheep at 30 min intervals each of three consecutive days. Hypothalamic, pituitary and thyroid glands were collected and preserved for further immunohistochemical and molecular biological analyses. Additionally, blood samples were collected during the experiment for subsequent RIA determinations. In summary, the results of the experiment have indicated that QRFP43 modulates the secretory activity of the HPT axis at all organisational levels. Moreover, QRFP43 can alter the mRNA expression profiles of DIO1, DIO2 and DIO3 in HPT tissues, leading to discrete changes in the metabolism of the cells studied and their response to signals transmitted by T4 and T3.
UnidecNMR: automatic peak detection for NMR spectra in 1-4 dimensions
Abstract To extract information from NMR experiments, users need to identify the number of resonances in the spectrum, together with characteristic features such as chemical shifts and intensities. In many applications, particularly those involving biomolecules, this procedure is typically a manual and laborious process. While many algorithms are available to tackle this problem, their performance tends to be inferior to that of an experienced user. Here, we introduce UnidecNMR, which identifies resonances in NMR spectra using deconvolution. We demonstrate its favourable performance on 1 and 2D simulated spectra, strongly overlapped 1D spectra of oligosaccharides and 2D HSQC, 3D HNCO, 3D HNCA and 3/4D methyl-methyl NOE experimental spectra from a range of proteins. UnidecNMR outperforms a number of freely available algorithms and provides results comparable to those generated manually. Introducing additional restraints, such as a 2D peak list when analysing 3 and 4D data and incorporating reflection symmetry in NOE analysis further improves the results. UnidecNMR outputs a back-calculated spectrum and a peak list, both of which can be easily examined using the supplied GUI. The software allows interactive processing using nmrPipe, allowing users to go directly from raw data to processed spectra with picked peak lists.
Antimicrobial susceptibility profiles of Mycoplasma hyosynoviae strains isolated from five European countries between 2018 and 2023
AbstractMycoplasma (M.) hyosynoviae is a facultative pathogen, causing arthritis in finisher pigs world-wide. In the absence of a commercial vaccine improvement of housing conditions and antibiotic therapy are the only options to alleviate the clinical signs. This study aimed to determine antibiotic susceptibility profiles of 106 M. hyosynoviae isolates against ten antibiotics licensed for veterinary use in cases of arthritis. The isolates were collected between 2018 and 2023 from five European countries: Austria (n = 20), Belgium (n = 20), Germany (n = 25), Hungary (n = 21) and Italy (n = 20). The minimal inhibitory concentrations (MIC) were determined by broth micro-dilution assay. The tested isolates were highly susceptible to tiamulin (MIC90 ≤ 0.039 µg/ml), tylvalosin (MIC90 ≤ 0.039 µg/ml) and lincomycin (MIC90 ≤ 0.25 µg/ml). Low concentrations of tylosin (MIC90 0.5 µg/ml) and tilmicosin (MIC90 1 µg/ml) inhibited the growth of the isolates. While moderate minimal inhibitory concentrations were detected for doxycycline (MIC90 0.312 µg/ml), oxytetracycline (MIC90 2 µg/ml), enrofloxacin (MIC90 0.625 µg/ml) and florfenicol (MIC90 2 µg/ml), only high concentrations of tulathromycin (MIC90 64 µg/ml) inhibited the growth of the isolates. Statistical analysis revealed significant differences between countries in case of enrofloxacin, where the Hungarian isolates showed the lowest MIC values, and the German isolates the highest MIC values among the tested countries. Our results show that European M. hyosynoviae isolates are generally susceptible to the tested antibiotics with the exception of tulathromycin. The country specific differences indicate the importance of regular susceptibility testing of isolates on a Pan-European level.
Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice
Formulation development and evaluation, in silico PBPK modeling and in vivo pharmacodynamic studies of clozapine matrix type transdermal patches
Activity of the mammalian DNA transposon piggyBat from Myotis lucifugus is restricted by its own transposon ends
AbstractMembers of the piggyBac superfamily of DNA transposons are widely distributed in host genomes ranging from insects to mammals. The human genome has retained five piggyBac-derived genes as domesticated elements although they are no longer mobile. Here, we have investigated the transposition properties of piggyBat from Myotis lucifugus, the only known active mammalian DNA transposon, and show that its low activity in human cells is due to subterminal inhibitory DNA sequences. Activity can be dramatically improved by their removal, suggesting the existence of a mechanism for the suppression of transposon activity. The cryo-electron microscopy structure of the piggyBat transposase pre-synaptic complex showed an unexpected mode of DNA binding and recognition using C-terminal domains that are topologically different from those of the piggyBac transposase. Here we show that structure-based rational re-engineering of the transposase through the removal of putative phosphorylation sites and a changed domain organization - in combination with truncated transposon ends - results in a transposition system that is at least 100-fold more active than wild-type piggyBat.
Regulation of fibronectin and collagens type I, III and VI by TNF-α, TGF-β, IL-13, and tofacitinib
DNA targeting by compact Cas9d and its resurrected ancestor
AbstractType II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a Cas9d nuclease (747 amino acids in length) in multiple functional states, revealing a stepwise process of DNA targeting involving a conformational switch in a REC2 domain insertion. Our structures provide insights into the intricately folded guide RNA which acts as a structural scaffold to anchor small, flexible protein domains for DNA recognition. The sgRNA can be truncated by up to ~25% yet still retain activity in vivo. Using ancestral sequence reconstruction, we generated compact nucleases capable of efficient genome editing in mammalian cells. Collectively, our results provide mechanistic insights into the evolution and DNA targeting of diverse type II CRISPR-Cas systems, providing a blueprint for future re-engineering of minimal RNA-guided DNA endonucleases.