Communications Biology最新文献

Investigating microorganisms in metal-enriched environments holds the potential to revolutionize the sustainable recovery of critical metals such as lanthanides (Ln³⁺). We observe Hyphomicrobium spp. as part of a Fe²⁺/Mn²⁺-oxidizing consortia native to the ferruginous bottom waters of a Ln³⁺-enriched lake in Czechia. Notably, one species shows similarities to recently discovered bacteria expressing proteins with picomolar Ln³⁺ affinity. This finding was substantiated by developing an in-silico ionic competition model and recombinant expression of a homolog protein (Hm-LanM) from Hyphomicrobium methylovorum. Biochemical assays validate Hm-LanM preference for lighter Ln³⁺ ions (from lanthanum to gadolinium). This is comparable to established prototypes. Bioinformatics analyses further uncover additional H. methylovorum metabolic biomolecules in genomic proximity to Hm-LanM analogously dependent on Ln³⁺, including an outer membrane receptor that binds Ln³⁺-chelating siderophores. These combined observations underscore the remarkable strategy of Hyphomicrobium spp. for thriving in relatively Ln³⁺ enriched zones of metal-polluted environments.

Wound healing is a highly coordinated spatiotemporal sequence of events involving several cell types and tissues. The process of wound healing requires strict regulation, and its disruption can lead to the formation of chronic wounds, which can have a significant impact on an individual's health as well as on worldwide healthcare expenditure. One essential aspect within the cellular and molecular regulation of wound healing pathogenesis is that of reactive oxygen species (ROS) and oxidative stress. Wounding significantly elevates levels of ROS, and an array of various reactive species are involved in modulating the wound healing process, such as through antimicrobial activities and signal transduction. However, as in many pathologies, ROS play an antagonistic pleiotropic role in wound healing, and can be a pathogenic factor in the formation of chronic wounds. Whilst advances in targeting ROS and oxidative stress have led to the development of novel pre-clinical therapeutic methods, due to the complex nature of ROS in wound healing, gaps in knowledge remain concerning the specific cellular and molecular functions of ROS in wound healing. In this review, we highlight current knowledge of these functions, and discuss the potential future direction of new studies, and how these pathways may be targeted in future pre-clinical studies.

Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.

Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist. Evidence suggests significant interactions between microglia and local microvasculature, potentially affecting blood-brain barrier integrity and cerebral blood flow regulation. Still, whether the microglial-vascular interface is affected in the brain during HF remains unknown. Using a well-established ischemic HF rat model, we demonstrate the increased abundance of vessel-associated microglia (VAM) in HF rat hippocampi, along with an increased expression of AngII AT1a receptors. Acute AngII administration to sham rats induced microglia recruitment to brain capillaries, along with increased expression of TNFα. Conversely, administering an AT1aR blocker to HF rats prevented the recruitment of microglia to blood vessels, normalizing their levels to those in healthy rats. These results highlight the critical importance of a rather understudied phenomenon (i.e., microglia-vascular interactions in the brain) in the context of the pathophysiology of a highly prevalent cardiovascular disease, and unveil novel potential therapeutic avenues aimed at mitigating neuroinflammation in cardiovascular diseases.

Insects rely on substrate vibrations in numerous intra- and interspecific interactions. Yet, our knowledge of noise impact in this modality lags behind that in audition, limiting our understanding of how anthropogenic noise affects insect communities. Auditory research has linked impaired signal perception in noise (i.e., masking) to spectral overlap. We investigated the impact of noise with different spectral compositions on the vibrational communication of the stink bug Nezara viridula, examining courtship behaviour and signal representation by sensory neurons. We found negative effects of vibrational noise regardless of spectral overlap, challenging common expectations. Noise impaired the ability of males to recognize the female signal and localise its source: overlapping noise decreased sensitivity of receptor neurons to the signal and disrupted signal frequency encoding by phase-locking units, while non-overlapping noise only affected frequency encoding. Modelling neuronal spike triggering in sensory neurons linked disrupted frequency encoding to interference-induced alterations of the signal waveform. These alterations also affected time delays between signal arrivals to different legs, crucial for localisation. Our study thus unveils a new masking mechanism, potentially unique to insect vibrosensory systems. The findings highlight the higher vulnerability of vibration-mediated behaviour to noise, with implications for insect interactions in natural and anthropogenically altered environments.

The interactions between zooplankton and viruses, which have been overlooked despite their crucial roles in marine ecosystems, are investigated in the copepod Pseudocalanus newmani. Copepod transcriptome data reveal four novel RNA viruses and weekly zooplankton samplings detect all viruses with different prevalence peaks during low-abundance periods of P. newmani. In addition to water temperature and food quality, our results suggest that marine virus is one of the factors controlling copepod population dynamics. Gene expression analysis indicates possible increased viral replication and decreased copepod movement in P. newmani with the Picorna-like virus, which is closely related to phytoplankton viruses, and metabarcoding diet analysis detects diatoms as P. newmani's major prey. Viral-like particles are observed in the gut contents of copepods during the high prevalence of this virus, suggesting infected copepod prey may affect copepod physiology. These results show that investigating zooplankton-virus interactions can provide a better understanding of marine ecosystems.

Dietary modifications to overcome infertility have attracted attention; however, scientifically substantiated information on specific dietary components affecting fertility and their mechanisms is limited. Herein, we investigated diet-induced, reversible infertility in female mice lacking the heterodimer of ATP-binding cassette transporters G5 and G8 (ABCG5/G8), which functions as a lipid exporter in the intestine. We found that dietary phytosterols, especially β-sitosterol and brassicasterol, which are substrates of ABCG5/G8, have potent but reversible reproductive toxicities in mice. Mechanistically, these phytosterols inhibited ovarian folliculogenesis and reduced egg quality by enhancing polycomb repressive complex 2-mediated histone H3 trimethylation at lysine 27 in the ovary. Clinical analyses showed that serum phytosterol levels were significantly and negatively correlated with the blastocyst development rate of fertilized eggs in women undergoing in vitro fertilization, suggesting that phytosterols affect egg quality in both humans and mice. Thus, avoiding excessive intake of certain phytosterols would be beneficial for female reproductive health.

The human brain is tightly connected to the individual's environment and its input dynamics. How the dynamics of periodic environmental stimuli influence neural activity and subsequent behavior via neural entrainment or alignment is not fully clear yet, though. This study explores how periodic environmental stimuli influence neural activity and behavior. EEG data was collected during a Go-NoGo task with a periodic intertrial interval (ITI) of 1.3 s (0.769 Hz). Results showed that the task's temporal structure increased power spectrum activity at 0.769 Hz, which showed high intersubject variability. Higher task-periodicity effects were linked to stronger phase-based intertrial coherence (ITC) and reduced neural complexity, as measured by lower Lempel-Ziv Complexity (LZC). Additionally, higher periodicity in the power spectrum correlated with faster reaction times and stronger response bias. We conclude that the encoding of the inputs' dynamics into the brains power spectrum shapes subsequent behavior, e.g., RT and response bias, through reducing neural complexity.

Psoriasis is a prevalent, inflammatory skin disease without cure. Further research is required to unravel dysregulated processes and develop new therapeutic interventions. The lack of suitable in vivo and in vitro preclinical models is an impediment in the psoriasis research. Recently, the development of 3D skin models has progressed including replicas with disease-like features. To investigate the use of in vitro models as preclinical test tools, the study focused on treatment responses of 3D skin replicas. Cytokine-priming of skin organoids induced psoriatic features like inflammation, antimicrobial peptides (AMP), hyperproliferation and impaired differentiation. Topical application of dexamethasone (DEX) or celastrol (CEL), a natural anti-inflammatory compound reduced the secretion of pro-inflammatory cytokines. DEX and CEL decreased the gene expression of inflammatory mediators. DEX barely affected the psoriatic AMP transcription but CEL downregulated psoriasis-driven AMP genes. Subcutaneous application of adalimumab (ADM) or bimekizumab (BMM) showed anti-psoriatic effects via protein induction of the differentiation marker keratin-10. Dual blockage of TNF-α and IL-17A repressed the inflammatory psoriasis phenotype. BMM inhibited the psoriatic expression of AMP genes and induced KRT10 and cell-cell contact genes. The present in vitro model provides a 3D environment with in vivo-like cutaneous responses and represents a promising tool for preclinical investigations.

Human organoids have been proposed to be powerful tools mimicking the physiopathological processes of the organs of origin. Recently, human pancreatic organoids (hPOs) have gained increasing attention due to potential theragnostic and regenerative medicine applications. However, the cellular components of hPOs have not been defined precisely. In this work, we finely characterized these structures, focusing first on morphology and identity-defining molecular features under long-term culture conditions. Next, we focused our attention on hPOs cell type composition using single-cell RNA sequencing founding a complex heterogeneity in ductal components, ranging from progenitor components to terminally differentiated ducts. Furthermore, an extensive comparison of human pancreatic organoids with previously reported transcriptomics signature of human and mouse pancreatic ductal populations, confirmed the functional pancreatic duct subpopulation heterogeneity. Finally, we showed that pancreatic organoid cells follow a precise developmental trajectory and utilize diverse signalling mechanisms, including EGF and SPP1, to facilitate cell-cell communication and maturation. Together our results offer an in-depth description of human pancreatic organoids providing a strong foundation for future in vitro diagnostic and translational studies of pancreatic health and disease.