J Chem Inf Model. 2023 Aug 2. doi: 10.1021/acs.jcim.3c00631. Online ahead of print.

ABSTRACT

Free energy perturbation coupled with replica exchange with solute tempering (FEP/REST) offers a rigorous approach to compute relative free energy changes for ligands. To determine the applicability of FEP/REST for the ligands with distributed binding poses, we considered two alchemical transformations involving three putative inhibitors I0, I1, and I2 of the Venezuelan equine encephalitis virus nuclear localization signal sequence binding to the importin-α (impα) transporter protein. I0 → I1 and I0 → I2 transformations, respectively, increase or decrease the polarity of the parent molecule. Our objective was three-fold─(i) to verify FEP/REST technical performance and convergence, (ii) to estimate changes in binding free energy ΔΔG, and (iii) to determine the utility of FEP/REST simulations for conformational binding analysis. Our results are as follows. First, our FEP/REST implementation properly follows FEP/REST formalism and produces converged ΔΔG estimates. Due to ligand inherent unbinding, the better FEP/REST strategy lies in performing multiple independent trajectories rather than extending their length. Second, I0 → I1 and I0 → I2 transformations result in overall minor changes in inhibitor binding free energy, slightly strengthening the affinity of I1 and weakening that of I2. Electrostatic interactions dominate binding interactions, determining the enthalpic changes. The two transformations cause opposite entropic changes, which ultimately govern binding affinities. Importantly, we confirm the validity of FEP/REST free energy estimates by comparing them with our previous REST simulations, directly probing binding of three ligands to impα. Third, we established that FEP/REST simulations can sample binding ensembles of ligands. Thus, FEP/REST can be applied (i) to study the energetics of the ligand binding without defined poses and showing minor differences in affinities |ΔΔG| ≲ 0.5 kcal/mol and (ii) to collect ligand binding conformational ensembles.

PMID:37531558 | DOI:10.1021/acs.jcim.3c00631

J Am Chem Soc. 2023 Aug 2. doi: 10.1021/jacs.3c02943. Online ahead of print.

ABSTRACT

Solid-binding peptides are a simple and versatile tool for the non-covalent modification of solid material surfaces, and a variety of peptides have been developed by reference to natural proteins or de novo design. Here, for the first time, we report the discovery of a bicyclic peptide targeting the heterogeneous material polypropylene by combining phage display technology and next-generation sequencing. We find that the enrichment properties of bicyclic peptides capable of binding to polypropylene are distinct from linear peptides, as reflected in amino acid abundance and a trend toward negative net charges and high hydrophobicity. The selected bicyclic peptide has a higher binding affinity for polypropylene compared with a previously reported linear peptide, enabling the hydrophilic and adhesive properties of the polypropylene to be more effectively enhanced. Our work paves the way for the exploration and utilization of conformational-restricted cyclic peptides as a new family of functionally evolvable agents for material surface modification.

PMID:37531461 | DOI:10.1021/jacs.3c02943

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2311012120. doi: 10.1073/pnas.2311012120. Epub 2023 Aug 2.

NO ABSTRACT

PMID:37531373 | DOI:10.1073/pnas.2311012120

PLoS One. 2023 Aug 2;18(8):e0288075. doi: 10.1371/journal.pone.0288075. eCollection 2023.

ABSTRACT

In 2018, a well-constructed cist-type grave was discovered at Ba`ja, a Neolithic village (7,400-6,800 BCE) in Southern Jordan. Underneath multiple grave layers, an 8-year-old child was buried in a fetal position. Over 2,500 beads were found on the chest and neck, along with a double perforated stone pendant and a delicately engraved mother-of-pearl ring discovered among the concentration of beads. The first was found behind the neck, and the second on the chest. The meticulous documentation of the bead distribution indicated that the assemblage was a composite ornament that had gradually collapsed, partly due to the burying position. Our aim was to challenge time degradation and to reimagine the initial composition in order to best explore the significance of this symbolic category of material culture, not as mere group of beads, but as an ornamental creation with further aesthetic, artisanal and socioeconomic implications. The reconstruction results exceeded our expectations as it revealed an imposing multi-row necklace of complex structure and attractive design. Through multiple lines of evidence, we suggest that the necklace was created at Ba`ja, although significant parts of beads were made from exotic shells and stones, including fossil amber, an unprecedented material never attested before for this period. The retrieval of such an ornament from life and its attribution to a young dead child highlights the significant social status of this individual. Beyond the symbolic functions related to identity, the necklace is believed to have played a key role in performing the inhumation rituals, understood as a public event gathering families, relatives, and people from other villages. In this sense, the necklace is not seen as belonging completely to the realm of death but rather to the world of the living, materializing a collective memory and shared moments of emotions and social cohesion.

PMID:37531349 | DOI:10.1371/journal.pone.0288075

N Engl J Med. 2023 Aug 3;389(5):406-417. doi: 10.1056/NEJMoa2302892.

ABSTRACT

BACKGROUND: The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health.

METHODS: We evaluated the risk of death, cancer, and autoimmune disease among adult patients who had undergone thymectomy as compared with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T-cell production and plasma cytokine levels were also compared in a subgroup of patients.

RESULTS: After exclusions, 1420 patients who had undergone thymectomy and 6021 controls were included in the study; 1146 of the patients who had undergone thymectomy had a matched control and were included in the primary cohort. At 5 years after surgery, all-cause mortality was higher in the thymectomy group than in the control group (8.1% vs. 2.8%; relative risk, 2.9; 95% confidence interval [CI], 1.7 to 4.8), as was the risk of cancer (7.4% vs. 3.7%; relative risk, 2.0; 95% CI, 1.3 to 3.2). Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2). In an analysis involving all patients with more than 5 years of follow-up (with or without a matched control), all-cause mortality was higher in the thymectomy group than in the general U.S. population (9.0% vs. 5.2%), as was mortality due to cancer (2.3% vs. 1.5%). In the subgroup of patients in whom T-cell production and plasma cytokine levels were measured (22 in the thymectomy group and 19 in the control group; mean follow-up, 14.2 postoperative years), those who had undergone thymectomy had less new production of CD4+ and CD8+ lymphocytes than controls (mean CD4+ signal joint T-cell receptor excision circle [sjTREC] count, 1451 vs. 526 per microgram of DNA [P = 0.009]; mean CD8+ sjTREC count, 1466 vs. 447 per microgram of DNA [P<0.001]) and higher levels of proinflammatory cytokines in the blood.

CONCLUSIONS: In this study, all-cause mortality and the risk of cancer were higher among patients who had undergone thymectomy than among controls. Thymectomy also appeared be associated with an increased risk of autoimmune disease when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis. (Funded by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund and others.).

PMID:37530823 | DOI:10.1056/NEJMoa2302892

J Cell Mol Med. 2023 Aug 2. doi: 10.1111/jcmm.17894. Online ahead of print.

ABSTRACT

Hydatidosis is a disease caused by the larval stage of Echinococcus granulosus, which involves several organs of intermediate hosts. Evidence suggests a communication between hydatid cyst (HC) and hosts via extracellular vesicles. However, a little is known about the communication between EVs derived from HC fluid (HCF) and host cells. In the current study, EVs were isolated using differential centrifugation from sheep HCF and characterized by western blot, electron microscope and size distribution analysis. The uptake of EVs by human monocyte cell line (THP-1) was evaluated. The effects of EVs on the expression levels of pro- and anti-inflammatory cytokines were investigated using quantitative real-time PCR (RT-PCR), 3 and 24 h after incubation. Moreover, the cytokine level of IL-10 was evaluated in supernatant of THP-1 cell line at 3 and 24 h. EVs were successfully isolated and showed spherical shape with size distribution at 130.6 nm. After 3 h, the expression levels of pro-inflammatory cytokine genes (IL1Β, IL15 and IL8) were upregulated, while after 24 h, the expression levels of pro-inflammatory cytokines were decreased and IL13 gene expression showed upregulation. A statistically significant increase was seen in the levels of IL-10 after 24 h. The main mechanism of the communication between EVs derived from HCF and their host remains unclear; however, time-dependent anti-inflammatory effects in our study suggest that HC may modulate the immune responses via EVs.

PMID:37530547 | DOI:10.1111/jcmm.17894

Plant Biotechnol J. 2023 Aug 2. doi: 10.1111/pbi.14136. Online ahead of print.

ABSTRACT

Millets are a class of nutrient-rich coarse cereals with high resistance to abiotic stress; thus, they guarantee food security for people living in areas with extreme climatic conditions and provide stress-related genetic resources for other crops. However, no platform is available to provide a comprehensive and systematic multi-omics analysis for millets, which seriously hinders the mining of stress-related genes and the molecular breeding of millets. Here, a free, web-accessible, user-friendly millets multi-omics database platform (Milletdb, http://milletdb.novogene.com) has been developed. The Milletdb contains six millets and their one related species genomes, graph-based pan-genomics of pearl millet, and stress-related multi-omics data, which enable Milletdb to be the most complete millets multi-omics database available. We stored GWAS (genome-wide association study) results of 20 yield-related trait data obtained under three environmental conditions [field (no stress), early drought and late drought] for 2 years in the database, allowing users to identify stress-related genes that support yield improvement. Milletdb can simplify the functional genomics analysis of millets by providing users with 20 different tools (e.g., 'Gene mapping', 'Co-expression', 'KEGG/GO Enrichment' analysis, etc.). On the Milletdb platform, a gene PMA1G03779.1 was identified through 'GWAS', which has the potential to modulate yield and respond to different environmental stresses. Using the tools provided by Milletdb, we found that the stress-related PLATZs TFs (transcription factors) family expands in 87.5% of millet accessions and contributes to vegetative growth and abiotic stress responses. Milletdb can effectively serve researchers in the mining of key genes, genome editing and molecular breeding of millets.

PMID:37530223 | DOI:10.1111/pbi.14136

Turk J Biol. 2023 May 23;47(3):208-217. doi: 10.55730/1300-0152.2656. eCollection 2023.

ABSTRACT

BACKGROUND/AIM: Dietary restriction, mainly carbon and/or methionine restriction are among the upcoming supporting interventions along with chemotherapy in various cancers. Although dietary restriction has been proven to be beneficial, the main cellular machineries affected by its administration lacks deeper information considerably, a notable pitfall in its use as a personalized nutritional approach.

MATERIALS AND METHODS: In this study, cellular effects of methionine restriction on a yeast model are explored via systems biology approaches. The methionine biosynthesis network, constructed by integrating interaction data with gene ontology terms, was analysed topologically, and proved to be informative about the intertwined relationship of methionine biosynthesis and cancer. Experimentally, effects of methionine restriction on the yeast model were explored in vivo, with transcriptome analyses.

RESULTS: The integrative analysis of the transcriptional data together with the reconstructed network gave insight into cellular machineries such as TOR, MAPK, and sphingolipid-mediated signaling cascades as the mostly responsive cellular pathways in the methionine-restricted cases with Sch9p (functional orthologue of mammalian S6 kinase) being placed at the intersection of these signaling routes.

PMID:37529420 | PMC:PMC10388026 | DOI:10.55730/1300-0152.2656

Front Plant Sci. 2023 Jul 17;14:1212073. doi: 10.3389/fpls.2023.1212073. eCollection 2023.

ABSTRACT

Plants have evolved various mechanisms to adapt to adverse environmental stresses, such as the modulation of gene expression. Expression of stress-responsive genes is controlled by specific regulators, including transcription factors (TFs), that bind to sequence-specific binding sites, representing key components of cis-regulatory elements and regulatory networks. Our understanding of the underlying regulatory code remains, however, incomplete. Recent studies have shown that, by training machine learning (ML) algorithms on genomic sequence features, it is possible to predict which genes will transcriptionally respond to a specific stress. By identifying the most important features for gene expression prediction, these trained ML models allow, in theory, to further elucidate the regulatory code underlying the transcriptional response to abiotic stress. Here, we trained random forest ML models to predict gene expression in rice (Oryza sativa) in response to heat or drought stress. Apart from thoroughly assessing model performance and robustness across various input training data, the importance of promoter and gene body sequence features to train ML models was evaluated. The use of enriched promoter oligomers, complementing known TF binding sites, allowed us to gain novel insights in DNA motifs contributing to the stress regulatory code. By comparing genomic feature importance scores for drought and heat stress over time, general and stress-specific genomic features contributing to the performance of the learned models and their temporal variation were identified. This study provides a solid foundation to build and interpret ML models accurately predicting transcriptional responses and enables novel insights in biological sequence features that are important for abiotic stress responses.

PMID:37528982 | PMC:PMC10390317 | DOI:10.3389/fpls.2023.1212073

Biophys J. 2023 Jul 31:S0006-3495(23)00477-0. doi: 10.1016/j.bpj.2023.07.026. Online ahead of print.

ABSTRACT

E-cadherin plays a central role in cell-cell adhesion. The ectodomains of wild type cadherins form a crystalline-like two dimensional lattice in cell-cell interfaces mediated by both trans (apposed cell) and cis (same cell) interactions. In addition to these extracellular forces, adhesive strength is further regulated by cytosolic phenomena involving α and β-catenin-mediated interactions between cadherin and the actin cytoskeleton. Cell-cell adhesion can be further strengthened under tension through mechanisms that have not been definitively characterized in molecular detail. Here we quantitatively determine the role of the cadherin ectodomain in mechanosensing. To this end, we devise an E-cadherin-coated emulsion system, in which droplet surface tension is balanced by protein binding strength to give rise to stable areas of adhesion. To reach the honeycomb/cohesive limit, an initial emulsion compression by centrifugation facilitates E-cadherin trans-binding, while a high protein surface concentration enables the cis-enhanced stabilization of the interface. We observe an abrupt concentration dependence on recruitment into adhesions of constant crystalline density, reminiscent of a first-order phase transition. Removing the lateral cis-interaction with a "cis mutant" shifts this transition to higher surface densities leading to denser, yet weaker adhesions. In both proteins, the stabilization of progressively larger areas of deformation is consistent with single-molecule experiments that show a force-dependent lifetime enhancement in the cadherin ectodomain, which may be attributed to the "X-dimer" bond.

PMID:37528581 | DOI:10.1016/j.bpj.2023.07.026

Sci Signal. 2023 Aug;16(796):eadg6474. doi: 10.1126/scisignal.adg6474. Epub 2023 Aug 1.

ABSTRACT

Notch signaling relies on ligand-induced proteolysis of the transmembrane receptor Notch to liberate a nuclear effector that drives cell fate decisions. Upon ligand binding, sequential cleavage of Notch by the transmembrane protease ADAM10 and the intracellular protease γ-secretase releases the Notch intracellular domain (NICD), which translocates to the nucleus and forms a complex that induces target gene transcription. To map the location and timing of the individual steps required for the proteolysis and movement of Notch from the plasma membrane to the nucleus, we used proximity labeling with quantitative, multiplexed mass spectrometry to monitor the interaction partners of endogenous NOTCH2 after ligand stimulation in the presence of a γ-secretase inhibitor and as a function of time after inhibitor removal. Our studies showed that γ-secretase-mediated cleavage of NOTCH2 occurred in an intracellular compartment and that formation of nuclear complexes and recruitment of chromatin-modifying enzymes occurred within 45 min of inhibitor washout. These findings provide a detailed spatiotemporal map tracking the path of Notch from the plasma membrane to the nucleus and identify signaling events that are potential targets for modulating Notch activity.

PMID:37527352 | DOI:10.1126/scisignal.adg6474

mSystems. 2023 Aug 1:e0089122. doi: 10.1128/msystems.00891-22. Online ahead of print.

ABSTRACT

Bacillus subtilis is a soil-dwelling bacterium that can form biofilms, or communities of cells surrounded by a self-produced extracellular matrix. In biofilms, genetically identical cells often exhibit heterogeneous transcriptional phenotypes, so that subpopulations of cells carry out essential yet costly cellular processes that allow the entire population to thrive. Surprisingly, the extent of phenotypic heterogeneity and the relationships between subpopulations of cells within biofilms of even in well-studied bacterial systems like B. subtilis remains largely unknown. To determine relationships between these subpopulations of cells, we created 182 strains containing pairwise combinations of fluorescent transcriptional reporters for the expression state of 14 different genes associated with potential cellular subpopulations. We determined the spatial organization of the expression of these genes within biofilms using confocal microscopy, which revealed that many reporters localized to distinct areas of the biofilm, some of which were co-localized. We used flow cytometry to quantify reporter co-expression, which revealed that many cells "multi-task," simultaneously expressing two reporters. These data indicate that prior models describing B. subtilis cells as differentiating into specific cell types, each with a specific task or function, were oversimplified. Only a few subpopulations of cells, including surfactin and plipastatin producers, as well as sporulating and competent cells, appear to have distinct roles based on the set of genes examined here. These data will provide us with a framework with which to further study and make predictions about the roles of diverse cellular phenotypes in B. subtilis biofilms. IMPORTANCE Many microbes differentiate, expressing diverse phenotypes to ensure their survival in various environments. However, studies on phenotypic differentiation have typically examined only a few phenotypes at one time, thus limiting our knowledge about the extent of differentiation and phenotypic overlap in the population. We investigated the spatial organization and gene expression relationships for genes important in B. subtilis biofilms. In doing so, we mapped spatial gene expression patterns and expanded the number of cell populations described in the B. subtilis literature. It is likely that other bacteria also display complex differentiation patterns within their biofilms. Studying the extent of cellular differentiation in other microbes may be important when designing therapies for disease-causing bacteria, where studying only a single phenotype may be masking underlying phenotypic differentiation relevant to infection outcomes.

PMID:37527273 | DOI:10.1128/msystems.00891-22

Cell Rep. 2023 Jul 31;42(8):112873. doi: 10.1016/j.celrep.2023.112873. Online ahead of print.

ABSTRACT

A vexing observation in genome-wide association studies (GWASs) is that parallel analyses in different species may not identify orthologous genes. Here, we demonstrate that cross-species translation of GWASs can be greatly improved by an analysis of co-localization within molecular networks. Using body mass index (BMI) as an example, we show that the genes associated with BMI in humans lack significant agreement with those identified in rats. However, the networks interconnecting these genes show substantial overlap, highlighting common mechanisms including synaptic signaling, epigenetic modification, and hormonal regulation. Genetic perturbations within these networks cause abnormal BMI phenotypes in mice, too, supporting their broad conservation across mammals. Other mechanisms appear species specific, including carbohydrate biosynthesis (humans) and glycerolipid metabolism (rodents). Finally, network co-localization also identifies cross-species convergence for height/body length. This study advances a general paradigm for determining whether and how phenotypes measured in model species recapitulate human biology.

PMID:37527041 | DOI:10.1016/j.celrep.2023.112873

Development. 2023 Aug 1:dev.201896. doi: 10.1242/dev.201896. Online ahead of print.

ABSTRACT

Developmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy levels in cardiac organ chambers. In Drosophila, differential growth and cell cycle signal sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume, cardiac output, and acceleration of circulating hemocytes. These Drosophila phenotypes mimic human cardiomyopathies. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery.

PMID:37526609 | DOI:10.1242/dev.201896

Cancer Res. 2023 Aug 1:CAN-23-0153. doi: 10.1158/0008-5472.CAN-23-0153. Online ahead of print.

ABSTRACT

Understanding the rewired metabolism underlying organ-specific metastasis in breast cancer could help identify strategies to improve the treatment and prevention of metastatic disease. Here, we used a systems biology approach to compare metabolic fluxes used by parental breast cancer cells and their brain- and lung-homing derivatives. Divergent lineages had distinct, heritable metabolic fluxes. Lung-homing cells maintained high glycolytic flux despite low levels of glycolytic intermediates, constitutively activating a pathway sink into lactate. This strong Warburg effect was associated with a high ratio of lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) expression, which correlated with lung metastasis in patients with breast cancer. While feature classification models trained on clinical characteristics alone were unable to predict tropism, the LDH/PDH ratio was a significant predictor of metastasis to the lung but not to other organs, independent of other transcriptomic signatures. High lactate efflux was also a trait in lung-homing metastatic pancreatic cancer cells, suggesting that lactate production may be a convergent phenotype in lung metastasis. Together, these analyses highlight the essential role that metabolism plays in organ-specific cancer metastasis and identify a putative biomarker for predicting lung metastasis in breast cancer patients.

PMID:37526524 | DOI:10.1158/0008-5472.CAN-23-0153

Soft Matter. 2023 Aug 1. doi: 10.1039/d3sm00566f. Online ahead of print.

ABSTRACT

The jamming transition is a nonequilibrium critical phenomenon, which governs characteristic mechanical properties of jammed soft materials, such as pastes, emulsions, and granular matters. Both experiments and theory of jammed soft materials have revealed that the complex modulus measured by conventional macrorheology exhibits a characteristic frequency dependence. Microrheology is a new type of method to obtain the complex modulus, which transforms the microscopic motion of probes to the complex modulus through the generalized Stokes relation (GSR). Although microrheology has been applied to jammed soft materials, its theoretical understanding is limited. In particular, the validity of the GSR near the jamming transition is far from obvious since there is a diverging length scale lc, which characterizes the heterogeneous response of jammed particles. Here, we study the microrheology of jammed particles by theory and numerical simulation. First, we develop a linear response formalism to calculate the response function of the probe particle, which is transformed to the complex modulus via the GSR. Then, we apply our formalism to a numerical model of jammed particles and find that the storage and loss modulus follow characteristic scaling laws near the jamming transition. Importantly, the observed scaling law coincides with that in macrorheology, which indicates that the GSR holds even near the jamming transition. We rationalize this equivalence by asymptotic analysis of the obtained formalism and numerical analysis on the displacement field of jammed particles under a local perturbation.

PMID:37525927 | DOI:10.1039/d3sm00566f

Drug Des Devel Ther. 2023 Jul 26;17:2193-2208. doi: 10.2147/DDDT.S414752. eCollection 2023.

ABSTRACT

Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.

PMID:37525853 | PMC:PMC10387245 | DOI:10.2147/DDDT.S414752

Adv Virus Res. 2023;116:45-88. doi: 10.1016/bs.aivir.2023.05.001. Epub 2023 Jul 10.

ABSTRACT

Individual functional viral morphogenesis events are often dynamic, short, and infrequent and might be obscured by other pathways and dead-end products. Volumetric live cell imaging has become an essential tool for studying viral morphogenesis events. It allows following entire dynamic processes while providing functional evidence that the imaged process is involved in viral production. Moreover, it allows to capture many individual events and allows quantitative analysis. Finally, the correlation of volumetric live-cell data with volumetric electron microscopy (EM) can provide crucial insights into the ultrastructure and mechanisms of viral morphogenesis events. Here, we provide an overview and discussion of suitable imaging methods for volumetric correlative imaging of viral morphogenesis and frame them in a historical summary of their development.

PMID:37524482 | DOI:10.1016/bs.aivir.2023.05.001

Curr Opin Plant Biol. 2023 Jul 29;75:102429. doi: 10.1016/j.pbi.2023.102429. Online ahead of print.

ABSTRACT

The plasma membrane (PM) houses a wide variety of proteins, facilitating interactions between the cell and its surroundings. Perception of external stimuli leads to selective internalization of membrane proteins via endocytosis. A multitude of endocytic signals affect protein internalization; however, their coordination and the exact mechanism of their recognition still remain elusive. In this review, we summarized the up-to-date knowledge of different internalization signals in PM cargo proteins and their involvement during protein trafficking.

PMID:37523901 | DOI:10.1016/j.pbi.2023.102429

J Neuroimmunol. 2023 Jul 25;382:578155. doi: 10.1016/j.jneuroim.2023.578155. Online ahead of print.

ABSTRACT

In this narrative review, we examine the association between gut dysbiosis, neuroinflammation, and stress-linked disorders, including depression, anxiety, and post-traumatic stress disorder (PTSD), and investigate whether tryptophan (TRP) metabolism and platelets play a role in this association. The mechanisms underlying the aetiology of stress-linked disorders are complex and not yet completely understood. However, a potential link between chronic inflammation and these disorders may potentially be found in TRP metabolism and platelets. By critically analysing existing literature on platelets, the gut microbiome, and stress-linked disorders, we hope to elicit the role of platelets in mediating the effects on serotonin (5-HT) levels and neuroinflammation. We have included studies specifically investigating platelets and TRP metabolism in relation to inflammation, neuroinflammation and neuropsychiatric disorders. Alteration in microbial composition due to stress could contribute to increased intestinal permeability, facilitating the translocation of microbial products, and triggering the release of pro-inflammatory cytokines. This causes platelets to become hyperactive and secrete 5-HT into the plasma. Increased levels of pro-inflammatory cytokines may also lead to increased permeability of the blood-brain barrier (BBB), allowing inflammatory mediators entry into the brain, affecting the balance of TRP metabolism products, such as 5-HT, kynurenic acid (KYNA), and quinolinic acid (QUIN). These alterations may contribute to neuroinflammation and possible neurological damage. Furthermore, platelets can cross the compromised BBB and interact with astrocytes and neurons, leading to the secretion of 5-HT and pro-inflammatory factors, exacerbating inflammatory conditions in the brain. The mechanisms underlying neuroinflammation resulting from peripheral inflammation are still unclear, but the connection between the brain and gut through the bloodstream could be significant. Identifying peripheral biomarkers and mechanisms in the plasma that reflect neuroinflammation may be important. This review serves as a foundation for further research on the association between the gut microbiome, blood microbiome, and neuropsychiatric disorders. The integration of these findings with protein and metabolite markers in the blood may expand our understanding of the subject.

PMID:37523892 | DOI:10.1016/j.jneuroim.2023.578155