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Fungal Biology Dec 2023Unlike the mechanism of ballistospore discharge, which was not solved until the 1980s, the operation of asci as pressurized squirt guns is relatively straightforward and... (Review)
Review
Unlike the mechanism of ballistospore discharge, which was not solved until the 1980s, the operation of asci as pressurized squirt guns is relatively straightforward and was understood in the nineteenth century. Since then, mycologists have sought to understand how structural adaptations to asci have allowed the ascomycetes to expel spores of different shapes and sizes over distances ranging from a few millimeters to tens of centimeters. These modifications include the use of valves at the tips of asci that maintain ascus pressure and expel spores at the highest speeds, and gelatinous appendages that connect spores after release and create larger projectiles with greater momentum than single spores. Clever experiments in the twentieth century coupled with meticulous microscopic studies led investigators to understand how asci with complicated apical structures worked and mathematical models produced estimates of launch speeds. With the recent application of high-speed video microscopy, these inferences about ascus function have been tested by imaging the motion of spores on a microsecond timescale. These experiments have established that ascospore discharge is the fastest fungal movement and is among the fastest movements in biology. Beginning with the history of the study of asci, this review article explains how asci are pressurized, how spores are released, and how far spores travel after their release. We also consider the efficiency of ascospore discharge relative to the mechanism of ballistospore discharge and examine the way that the squirt gun mechanism has limited the morphological diversity of ascomycete fruit bodies.
Topics: Firearms; Ascomycota; Spores, Fungal
PubMed: 38097323
DOI: 10.1016/j.funbio.2023.11.001 -
Microbiome Nov 2023Many studies have investigated how nanoplastics (NPs) exposure mediates nerve and intestinal toxicity through a dysregulated brain-gut axis interaction, but there are...
BACKGROUND
Many studies have investigated how nanoplastics (NPs) exposure mediates nerve and intestinal toxicity through a dysregulated brain-gut axis interaction, but there are few studies aimed at alleviating those effects. To determine whether and how vitamin D can impact that toxicity, fish were supplemented with a vitamin D-low diet and vitamin D-high diet.
RESULTS
Transmission electron microscopy (TEM) showed that polystyrene nanoplastics (PS-NPs) accumulated in zebrafish brain and intestine, resulting in brain blood-brain barrier basement membrane damage and the vacuolization of intestinal goblet cells and mitochondria. A high concentration of vitamin D reduced the accumulation of PS-NPs in zebrafish brain tissues by 20% and intestinal tissues by 58.8% and 52.2%, respectively, and alleviated the pathological damage induced by PS-NPs. Adequate vitamin D significantly increased the content of serotonin (5-HT) and reduced the anxiety-like behavior of zebrafish caused by PS-NPs exposure. Virus metagenome showed that PS-NPs exposure affected the composition and abundance of zebrafish intestinal viruses. Differentially expressed viruses in the vitamin D-low and vitamin D-high group affected the secretion of brain neurotransmitters in zebrafish. Virus AF191073 was negatively correlated with neurotransmitter 5-HT, whereas KT319643 was positively correlated with malondialdehyde (MDA) content and the expression of cytochrome 1a1 (cyp1a1) and cytochrome 1b1 (cyp1b1) in the intestine. This suggests that AF191073 and KT319643 may be key viruses that mediate the vitamin D reduction in neurotoxicity and immunotoxicity induced by PS-NPs.
CONCLUSION
Vitamin D can alleviate neurotoxicity and immunotoxicity induced by PS-NPs exposure by directionally altering the gut virome. These findings highlight the potential of vitamin D to alleviate the brain-gut-virome disorder caused by PS-NPs exposure and suggest potential therapeutic strategies to reduce the risk of NPs toxicity in aquaculture, that is, adding adequate vitamin D to diet. Video Abstract.
Topics: Animals; Polystyrenes; Zebrafish; Vitamin D; Nanoparticles; Microplastics; Serotonin; Virome; Water Pollutants, Chemical; Brain; Cytochromes
PubMed: 38008755
DOI: 10.1186/s40168-023-01680-1 -
Cell Communication and Signaling : CCS Oct 2023The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it...
BACKGROUND
The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified.
METHODS
We used mass spectrometry-based thermal proteome profiling in order to identify target proteins of prodigiosin. For target validation, we employed a genetic knockout approach and electron microscopy.
RESULTS
We identified the Golgi stacking protein GRASP55 as target protein of prodigiosin. We show that prodigiosin treatment severely affects Golgi morphology and functionality, and that prodigiosin-dependent cytotoxicity is partially reduced in GRASP55 knockout cells. We also found that prodigiosin treatment results in decreased cathepsin activity and overall blocks autophagic flux, whereas co-localization of the autophagosomal marker LC3 and the lysosomal marker LAMP1 is clearly promoted. Finally, we observed that autophagosomes accumulate at GRASP55-positive structures, pointing towards an involvement of an altered Golgi function in the autophagy-inhibitory effect of this natural compound.
CONCLUSION
Taken together, we propose that prodigiosin affects autophagy and Golgi apparatus integrity in an interlinked mode of action involving the regulation of organelle alkalization and the Golgi stacking protein GRASP55. Video Abstract.
Topics: Humans; Prodigiosin; Golgi Apparatus; Lysosomes; Autophagosomes; Autophagy
PubMed: 37798768
DOI: 10.1186/s12964-023-01275-1 -
Journal of Biomedical Optics Jun 2024Full-field optical coherence microscopy (FF-OCM) is a prevalent technique for backscattering and phase imaging with epi-detection. Traditional methods have two...
SIGNIFICANCE
Full-field optical coherence microscopy (FF-OCM) is a prevalent technique for backscattering and phase imaging with epi-detection. Traditional methods have two limitations: suboptimal utilization of functional information about the sample and complicated optical design with several moving parts for phase contrast.
AIM
We report an OCM setup capable of generating dynamic intensity, phase, and pseudo-spectroscopic contrast with single-shot full-field video-rate imaging called bichromatic tetraphasic (BiTe) full-field OCM with no moving parts.
APPROACH
BiTe OCM resourcefully uses the phase-shifting properties of anti-reflection (AR) coatings outside the rated bandwidths to create four unique phase shifts, which are detected with two emission filters for spectroscopic contrast.
RESULTS
BiTe OCM overcomes the disadvantages of previous FF-OCM setup techniques by capturing both the intensity and phase profiles without any artifacts or speckle noise for imaging scattering samples in three-dimensional (3D). BiTe OCM also utilizes the raw data effectively to generate three complementary contrasts: intensity, phase, and color. We demonstrate BiTe OCM to observe cellular dynamics, image live, and moving micro-animals in 3D, capture the spectroscopic hemodynamics of scattering tissues along with dynamic intensity and phase profiles, and image the microstructure of fall foliage with two different colors.
CONCLUSIONS
BiTe OCM can maximize the information efficiency of FF-OCM while maintaining overall simplicity in design for quantitative, dynamic, and spectroscopic characterization of biological samples.
Topics: Animals; Microscopy; Tomography, Optical Coherence; Microscopy, Phase-Contrast
PubMed: 38584966
DOI: 10.1117/1.JBO.29.S2.S22704 -
Archives of Dermatological Research Apr 2024This paper explores the role of teledermatology (TD) in Mohs micrographic surgery (MMS) at various stages of patient care. The study aims to assess the benefits,... (Review)
Review
This paper explores the role of teledermatology (TD) in Mohs micrographic surgery (MMS) at various stages of patient care. The study aims to assess the benefits, limitations, and patient experiences surrounding TD integration into MMS practices. We conducted a PubMed search using keywords related to TD and MMS, categorizing selected articles into pre-operative, intra-operative, and post-operative stages of MMS. TD reduced waiting times (26.10 days for TD compared to 60.57 days for face-to-face [FTF]) and consultation failure rates (6% for TD vs. 17% for FTF) for MMS preoperative consultations. It also shortened time to treatment by two weeks and led to notable travel savings (162.7 min, 144.5 miles, and $60.00 per person). Telepathology facilitated communication and decision-making during MMS, improving accuracy and efficiency, especially in challenging cases requiring collaboration where physical presence of another surgeon or pathologist is not feasible. Telepathology definitively diagnosed benign lesions and malignant tumors in 81.8% of cases (18/22). Additionally, there was a 95% agreement between conventional light microscopy diagnosis and telepathology in tumors (19/20), and 100% agreement for all 20 Mohs frozen section consultations. For post-operative follow-up, telephone follow-up (TFU) and text messaging proved effective, cost-efficient alternatives with high patient satisfaction (94% in New Zealand and 96% in the U.K.) and early complication identification. This study underscores TD's multifaceted benefits in MMS: enhanced patient experience preoperatively, improved communication during surgery, and cost-effective postoperative follow-up. Limitations include the financial expense and technical issues that can arise with TD (connectivity problems, delays in video/audio transmission, etc.). Further studies are needed to explore emerging TD modalities in post-operative patient management. The integration of TD into MMS signifies a progressive step in dermatological care, offering convenient, cost-effective, and better solutions with the potential to enhance patient experiences and outcomes.
Topics: Humans; Mohs Surgery; Communication; New Zealand; Pathologists; Patient Satisfaction
PubMed: 38625403
DOI: 10.1007/s00403-024-02851-2 -
Nature Communications Oct 2023Antigen cognate dendritic cell (DC)-T cell synaptic interactions drive activation of T cells and instruct DCs. Upon receiving CD4 T cell help, post-synaptic DCs (psDCs)...
Antigen cognate dendritic cell (DC)-T cell synaptic interactions drive activation of T cells and instruct DCs. Upon receiving CD4 T cell help, post-synaptic DCs (psDCs) are licensed to generate CD8 T cell responses. However, the cellular and molecular mechanisms that enable psDCs licensing remain unclear. Here, we describe that antigen presentation induces an upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs in vitro and in vivo. We also show that these events mediate DC licensing. In addition, psDC adoptive transfer enhances pathogen-specific CD8 T responses and protects mice from infection in a CD8 T cell-dependent manner. Conversely, depletion of psDCs in vivo abrogates antigen-specific CD8 T cell responses during immunization. Together, our data show that psDCs enable CD8 T cell responses in vivo during vaccination and reveal crucial molecular events underlying psDC licensing.
Topics: Mice; Animals; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Up-Regulation; Lipid Peroxidation; Antigen Presentation; Antigens; Histocompatibility Antigens Class I; Dendritic Cells; Synapses; Mice, Inbred C57BL
PubMed: 37880206
DOI: 10.1038/s41467-023-42480-3 -
Cancers Nov 2023Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment...
Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment regardless of the clinical stage. New imaging techniques, such as in vivo reflectance confocal microscopy (RCM), significantly increase the accuracy of diagnosis and allow noninvasive evaluation of the therapeutic efficacy of the ongoing treatment. Our objective was to evaluate the prevalence of specific (video)dermoscopy and RCM features of pigmented and classical subtypes of AK before and after photodynamic therapy (PDT) treatment. We included patients with facial grade II AKs (25 pigmented, 275 non-pigmented) were included in the study. Skin lesions were evaluated by (video)dermoscopy and RCM at the baseline and three months after PDT. In classic AK, the most frequent dermoscopic findings were fine wavy vessels (96%), scale (92%), microerosions (48%), and "strawberry" pattern (36%), while pigmented AK was characterized mostly by "rhomboidal pattern" (80%), scale (60%), white globules (48%), "jelly sign", and superficial pigmentation (40%). RCM's most characteristic classic AK findings were abnormal honeycomb pattern in the spinous layer, epidermal inflammatory infiltrate, and solar elastosis that were present in 96% of lesions. Pigmented AKs presented mostly with dark central areas of parakeratosis (72%), mottled pigmentation (72%), dermal inflammatory infiltrate (64%), solar elastosis (60%), and abnormal honeycomb pattern in the spinous layer (56%). Dermoscopically, PDT resulted in complete disappearance of the "rhomboidal pattern" in both classical and pigmented AKs, "starburst pattern" and "jelly sign" in classical AKs, and inner gray halo, "rosette sign" and central crust in pigmented AKs. Three months after one PDT session, RCM evaluation showed mostly solar elastosis in both classical and pigmented AK subtypes, epidermal inflammatory infiltrate in classical AKs, and dermal inflammatory infiltrate in pigmented AKs. New noninvasive imaging techniques such as RCM and (video)dermoscopy can help practitioners better visualize the efficacy of the ongoing PDT treatment in either classical or pigmented AK subtypes.
PubMed: 38067302
DOI: 10.3390/cancers15235598 -
Cell Communication and Signaling : CCS Jul 2023Extracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the...
BACKGROUND
Extracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the creation of a favorable tumor microenvironment. So far, EV uptake and cargo delivery into target cells have been regarded as the main mechanisms for the pro-tumoral function of EVs. To test this hypothesis, we investigated the fate of the oncogenic transmembrane Wnt tyrosine kinase-like orphan receptor 1 and 2 (ROR1, ROR2) delivered via distinct EV subpopulations to breast cancer cells and aimed to unravel their impact on tumor progression.
METHODS
EVs were isolated by differential ultracentrifugation from cell culture supernatant as well as plasma samples from healthy individuals (n = 27) and breast cancer patients (n = 41). EVs were thoroughly characterized by electron microscopy, nanoparticle tracking analysis, immunoblot, and flow cytometry. ROR transfer to target cells was observed using microscopy-based assays and biodistribution experiments were conducted in syngeneic mice. EV impact on cancer cell migration and invasion was tested in functional assays.
RESULTS
We observed that the supernatant of ROR-overexpressing cells was sufficient for transferring the receptors to ROR-negative cells. Analyzing the secretome of the ROR-overexpressing cells, we detected a high enrichment of ROR1/2 on large and small EVs, but not on large oncosomes. Interestingly, the majority of ROR-positive EVs remained attached to the target cell surface after 24 h of stimulation and was quickly removed by treatment with trypsin. Nonetheless, ROR-positive EVs increased migration and invasion of breast cancer cells, even after chemically inhibiting EV uptake, in dependence of RhoA downstream signaling. In vivo, ROR-depleted EVs tended to distribute less into organs prone for the formation of breast cancer metastases. ROR-positive EVs were also significantly elevated in the plasma of breast cancer patients and allowed to separate them from healthy controls.
CONCLUSIONS
The oncogenic Wnt receptors ROR1/2 are transferred via EVs to the surface of ROR-negative cancer cells, in which they induce an aggressive phenotype supporting tumor progression. Video Abstract.
Topics: Animals; Mice; Extracellular Vesicles; Protein-Tyrosine Kinases; Skin Neoplasms; Tissue Distribution; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 37430307
DOI: 10.1186/s12964-023-01186-1 -
Journal of Colloid and Interface Science Nov 2023Understanding how soft colloids, such as food emulsion droplets, transform based on their environment is critical for various applications, including drug and nutrient...
HYPOTHESIS
Understanding how soft colloids, such as food emulsion droplets, transform based on their environment is critical for various applications, including drug and nutrient delivery and biotechnology. However, the mechanisms behind colloidal transformations within individual oil droplets still need to be better understood.
EXPERIMENTS
This study employs optical micromanipulation with microfluidics and polarized optical video microscopy to investigate the pancreatic lipase- and pH-triggered colloidal transformations in a single triolein droplet. Small-angle X-ray scattering (SAXS) provides complementary statistical insights and allows for detailed structural assignment.
FINDINGS
Optical video microscopy recorded the transformation of individual triolein emulsion droplets, with the smooth surface of these spherical particles becoming rough and the entire volume eventually being affected. The polarized microscopy revealed the coexistence of at least two distinct structures in a single particle during digestion, with their ratio and distribution altered by pH. The SAXS analysis assigned the optical anisotropy to emulsified inverse hexagonal- and multilamellar phases, coexisting with isotropic structures such as the micellar cubic phase. These results can help understand the phase transformations inside an emulsion droplet during triglyceride digestion and guide the design of advanced food emulsions.
PubMed: 37406476
DOI: 10.1016/j.jcis.2023.06.022 -
Cell Communication and Signaling : CCS Jan 2024Cardiolipin (CL) plays a critical role in maintaining mitochondrial membrane integrity and overall mitochondrial homeostasis. Recent studies have suggested that...
BACKGROUND
Cardiolipin (CL) plays a critical role in maintaining mitochondrial membrane integrity and overall mitochondrial homeostasis. Recent studies have suggested that mitochondrial damage resulting from abnormal cardiolipin remodelling is associated with the pathogenesis of diabetic kidney disease (DKD). Acyl-coenzyme A:lyso-cardiolipin acyltransferase-1 (ALCAT1) was confirmed to be involved in the progression of Parkinson's disease, diet-induced obesity and other ageing-related diseases by regulating pathological cardiolipin remodelling. Thus, the purpose of this investigation was to determine the role of ALCAT1-mediated CL remodelling in DKD and to explore the potential underlying mechanism.
METHODS
In vivo study, the mitochondrial structure was examined by transmission electron microscopy (TEM). The colocalization of ALCAT1 and synaptopodin was evaluated by double immunolabelling. Western blotting (WB) was performed to assess ALCAT1 expression in glomeruli. Lipidomics analysis was conducted to evaluate the composition of reconstructed cardiolipins. In vitro study, the lipidomics, TEM and WB analyses were similar to those in vivo. Mitochondrial function was evaluated by measuring the mitochondrial membrane potential (MMP) and the production of ATP and ROS.
RESULTS
Here, we showed that increased oxidized cardiolipin (ox-CL) and significant mitochondrial damage were accompanied by increased ALCAT1 expression in the glomeruli of patients with DKD. Similar results were found in db/db mouse kidneys and in cultured podocytes stimulated with high glucose (HG). ALCAT1 deficiency effectively prevented HG-induced ox-CL production and mitochondrial damage in podocytes. In contrast, ALCAT1 upregulation enhanced ox-CL levels and podocyte mitochondrial dysfunction. Moreover, treatment with the cardiolipin antioxidant SS-31 markedly inhibited mitochondrial dysfunction and cell injury, and SS-31 treatment partly reversed the damage mediated by ALCAT1 overexpression. We further found that ALCAT1 could mediate the key regulators of mitochondrial dynamics and mitophagy through the AMPK pathway.
CONCLUSIONS
Collectively, our studies demonstrated that ALCAT1-mediated cardiolipin remodelling played a crucial role in DKD, which might provide new insights for DKD treatment. Video Abstract.
Topics: Animals; Humans; Mice; Cardiolipins; Diabetes Mellitus; Diabetic Nephropathies; Mitochondria; Mitochondrial Diseases; Podocytes
PubMed: 38200543
DOI: 10.1186/s12964-023-01399-4