Communications Biology最新文献

White-rot fungi are efficient organisms for the mineralization of lignin and polysaccharides into CO₂ and H₂O. Despite their biotechnological potential, WRF metabolism remains underexplored. Building on recent findings regarding the utilization of lignin-related aromatic compounds as carbon sources by WRF, we aimed to gain further insights into these catabolic processes. For this purpose, Trametes versicolor and Gelatoporia subvermispora were incubated in varying conditions - in static and agitation modes and different antioxidant levels - during the conversion of 4-hydroxybenzoic acid (a lignin-related compound) and cellobiose. Their metabolic responses were assessed via transcriptomics, proteomics, lipidomics, metabolomics, and microscopy analyses. These analyses reveal the significant impact of cultivation conditions on sugar and aromatic catabolic pathways, as well as lipid composition of the fungal mycelia. Additionally, this study identifies biosynthetic pathways for the production of extracellular fatty acids and phenylpropanoids - both products with relevance in biotechnological applications - and provides insights into carbon fate in nature.

Histone deacetylase 8 (HDAC8) is a well-known epigenetic regulator for cancer therapy. However, developing targeted inhibitors for HDAC8 is challenging due to a limited understanding of its structural dynamics, which is crucial for ligand interaction. Here, we employed an integrated approach, including native mass spectrometry (native MS), hydrogen-deuterium exchange mass spectrometry (HDX-MS), and molecular dynamics (MD) simulation, to investigate the inhibition mechanism and dynamic regulation of human HDAC8 (hHDAC8) by selective inhibitor PCI-34051, compared with the pan-inhibitor SAHA. Our results revealed that PCI-34051 engages with an expanded set of residues and conforms more aptly to the binding channel of hHDAC8, stabilizing the flexible loops surrounding the binding channel. Moreover, this dynamic stabilization effect is not limited to the binding regions, but also extends to distant regions (such as L2, α5, and α1 + α2), with L3 serving as a critical structural bridge. Overall, these results show the structural and dynamic regulations of hHDAC8 by PCI-34051, which induces a lower energy state for the protein-ligand system compared to SAHA, thus showing better inhibitory effects. In addition, it also suggests that certain regions, specifically loops L2 and L3, within the hHDAC8 protein could be key regions for targeted intervention.

Bacteriophage Sf14 infects the human pathogen Shigella flexneri. A previous low-resolution structure suggested the presence of a decoration protein on its T = 9 icosahedral capsid. Here, we determined high-resolution structures of the Sf14 capsid and neck, along with a moderate-resolution structure of the whole Sf14 tail and baseplate. These structures indicate the capsid has not one, but two different types of decoration proteins: a trimeric β-tulip lattice that covers the entire capsid and a set of Hoc-like proteins that bind preferentially to hexamers at the quasi-3-fold axes of symmetry. The neck also contains two sets of whiskers oriented in opposite directions, and the tail has two types of long tail fibers which may bind different receptors. Based on homology and phylogenetic analysis, Sf14 may be the product of multiple horizontal gene transfer events. The structures presented here can be used to investigate further hypotheses of phage structure-function relationships and structural diversity.

The ability to accurately monitor the quality of one's choices, or metacognition, improves under speed pressure, possibly due to changes in post-decisional evidence processing. Here, we investigate the neural processes that regulate decision-making and metacognition under speed pressure using time-resolved analyses of brain activity recorded using electroencephalography. Participants performed a motion discrimination task under short and long response deadlines and provided a metacognitive rating following each response. Behaviourally, participants were faster, less accurate, and showed superior metacognition with short deadlines. These effects were accompanied by a larger centro-parietal positivity (CPP), a neural correlate of evidence accumulation. Crucially, post-decisional CPP amplitude was more strongly associated with participants' metacognitive ratings following errors under short relative to long response deadlines. Our results suggest that superior metacognition under speed pressure may stem from enhanced metacognitive readout of post-decisional evidence.

Light functions as the universal language in the deep sea (>200 m). Both bioluminescent emissions and downwelling light sources dimly illuminate the water column and can drive sensory system evolution. In pelagic environments, vertically migrating animals can experience drastic changes to their lighting environment across depth, subjecting them to unique selective pressures, possibly to distinguish between changes in ambient light and bioluminescent sources. Here we show that visual opsin diversity across a group of variable vertical migrators -bioluminescent deep-sea shrimp belonging to the Superfamily Oplophoroidea- is higher among species who migrate to shallower waters with more variable light conditions. Further, we provide evidence for adaptive visual evolution among species who have evolved an additional mode of bioluminescence (photophores), including positive selection for a putative mid-wavelength sensitive opsin that may facilitate light source discrimination. Diversification of this opsin appears to play an important role in the visual ecologies of photophore-bearing shrimp with its diversification in Oplophoroidea likely playing a critical role in the fitness and evolutionary success of this group.

The ancestry composition and Sinicisation process of the descendants of the immigrants of Hu people living in ancient China are largely unknown due to the lack of genetic evidence. Tang Dynasty people in Fudamen cemetery () excavated from Shandong province in eastern China are believed to be related to the descendants of Hu people, as some of the individuals with the surnames An (). The genetic origin of the Fudamen population requires genetic clarification using ancient DNA data. Here we successfully obtain genome-wide SNP data for 17 Tang dynasty individuals from Fudamen cemetery. Based on autosomal data, although all Fudamen individuals show high levels of middle reaches of Yellow River-related ancestry as previously published historical period Shandong populations, 2 Fudamen individuals require ~5% Western Eurasian/Central Asian-related ancestry to describe their ancestry composition best. To the best of our knowledge, it is the first evidence of such ancestry in Shandong, the eastern part of today's China. Moreover, the admixture pattern is also reflected by the presence of both west and east Eurasian-specific mtDNA and Y chromosomal haplogroups in Fudamen people. The estimated admixture time is also consistent with periods when Sogdians and other non-Han populations were active in ancient China. These genomic findings suggest that intermarriage with Han Chinese involved the Sinicization process of the Hu people.

The long QT syndrome type 3 (LQT3) is a cardiac channelopathy caused by gain-of-function mutations in the SCN5A gene, encoding the sodium channel Na_v1.5. As Na_v1.5 is expressed in cardiomyocytes but also in cardiac fibroblasts, we investigated whether the LQT3-causing p.ΔQKP1507-1509 (ΔQKP) SCN5A mutation alters cardiac fibroblast phenotype. Primary cultured ventricular fibroblasts from Scn5a^+/ΔQKP knock-in mice showed increased proliferation, survival, expression of transforming growth factor-β (TGF-β) and activation of its canonical pathway, and reduced α-smooth muscle actin expression. Ventricular tissue from Scn5a^+/ΔQKP mice exhibited augmented fibroblast populations and fibrosis. Inhibiting TGF-β receptor, sodium current or Scn5a expression decreased Scn5a^+/ΔQKP fibroblast proliferation, while veratridine increased proliferation of control fibroblasts, mimicking Na_v1.5 gain-of-function. Lastly, abnormal calcium signaling underlied the increased proliferation of Scn5a^+/ΔQKP fibroblasts. Our study shows that cardiac fibroblasts carrying the ΔQKP-SCN5A mutation exhibit an abnormal, proliferative phenotype, paving the way for better understanding the role of cardiac fibroblasts in LQT3.

Human and animal health rely on balancing cell division and cell death to maintain normal homeostasis. This process is accomplished by regulated cell death (RCD), whose imbalance can lead to disease. Currently, the most frequently used method for analyzing RCD is fluorescence microscopy. This method has limitations and potential side effects due to the presence of fluorescent labels. Furthermore, fluorescence often lacks specificity and may have side effects. In the quest to overcome such difficulties, label-free approaches have come into focus.Here, Raman microscopy in combination with machine learning is used to investigate RCDs, where biochemical molecular "fingerprints" are investigated with a focus on the vibrations of atoms in molecules. Three different and unique RCD types with different genetic and biochemical machinery, namely, ferroptosis is studied in comparison with apoptosis, and necroptosis in the murine fibroblast line L929sAhFas. Interestingly, during ferroptosis, a decrease in the wavenumber at 939 cm^-1 was observed, which is associated with a potential reduction in the expression of collagen - a compound essential in multiple diseases. Data analysis was performed by machine learning (ML), here SVMs, where the model utilizing the spectra directly into a support vector machine (SVM) outperforms other SVM strategies correctly predicting 73% of all spectra. Other methods: PCA-SVM (principal component analysis-SVM), peak fitting-AUC-SVM (area under the curve) and peak fitting-spectral reconstruction-SVM rendered prediction accuracies of ~52%, ~43%, and 61%, respectively. Peak fitting has the additional benefit of enabling the biological interpretation of Raman scattering peaks by using the area under the curve, although at a loss of general accuracy. The potential of Raman microscopy in biology, in combination with machine learning pipelines, can be applied to a broader field of cell biology, not limited to regulated cell death.

The pig is an important animal model increasingly used for biomedical research, particularly in transplantation strategies involving xenotransplantation or the development of human organs in pig for exotransplantation. Pigs, however, are less characterized than other animal models. In this study, we produced wildtype (WT) pig embryos via somatic cell nuclear transfer (SCNT) technology and compared them to skeletal muscle null embryos (lacking MYF5/MYOD/MYF6) at embryonic day 41, 62, and 90, critical stages of porcine myogenesis. Magnetic resonance imaging (MRI) and histological analyses revealed progressive development of skeletal muscle in WT embryos but not in null embryos whereas development of viscera progressed equally in both groups. Molecular analyses highlighted dynamic changes in myogenic gene expression and myofiber formation, demonstrating an organized progression of myogenesis in WT embryos. Morphologically, the null embryos exhibited abnormalities, including marked edema and underdeveloped limbs. MRI revealed severe skeletal abnormalities, including the absence of ribs, sternum, and associated vertebral malformations. In addition, histological analysis confirmed the complete lack of myofiber formation. Immunohistochemical analysis revealed the absence of myogenic stem cells and muscle differentiation, and RNA sequencing demonstrated that the skeletal muscle development process was entirely disrupted in null embryos. Additionally, analysis of neuromuscular junctions (NMJs) in the null embryos revealed that functional NMJ formation was absent, consistent with the lack of skeletal muscle formation. Importantly, these defects culminated in embryonic lethality after day 62 in the null embryos. We determined that the myogenic regulatory gene cascade is crucial for porcine embryo development and viability. The deletion of skeletal muscle is essential for the creating a vacant niche to allow for complementation of null porcine embryos with human induced pluripotent stem cells. Characterization of this skeletal muscle null pig model provide an important platform for engineering humanized muscle in gene-edited pigs.