J Exp Bot. 2025 Jan 8:eraf005. doi: 10.1093/jxb/eraf005. Online ahead of print.

ABSTRACT

The complex gene regulatory landscape underlying early flower development in Arabidopsis has been extensively studied through transcriptome profiling, and gene networks controlling floral organ development have been derived from the analyses of genome wide binding of key transcription factors. In contrast, the dynamic nature of the proteome during the flower development process is much less understood. In this study, we characterized the floral proteome at different stages during early flower development and correlated it with unbiased transcript expression data. Shotgun proteomics and transcript profiling were conducted using an APETALA1-based floral induction system. A specific analysis pipeline to process the time-course proteomics data was developed. In total, 8,924 proteins and 23,069 transcripts were identified. Co-expression analysis revealed that RNA-protein pairs clustered in various expression pattern modules. An overall positive correlation between RNA and protein level changes was observed, but subgroups of RNA/protein pairs with anticorrelated gene expression changes were also identified and found to be enriched in hormone responsive pathways. In addition, the RNA-seq dataset reported here further expanded the identification of genes whose expression changes during early flower development, and its combination with previously published AP1 ChIP-seq datasets allowed the identification of additional AP1 direct and high-confidence targets.

PMID:39774695 | DOI:10.1093/jxb/eraf005

Anesth Analg. 2024 Nov 19. doi: 10.1213/ANE.0000000000007293. Online ahead of print.

ABSTRACT

BACKGROUND: Delirium after cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. In this study, we aimed to identify protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery.

METHODS: SomaScan analysis of 1305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (preoperative baseline timepoint [PREOP]) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the Enzyme-Linked Lectin Assay (ELLA) multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology.

RESULTS: Of the 115 patients, 21 (18.3%) developed delirium after surgery. The SomaScan proteome screening evidenced differential expression of 115 and 85 proteins in delirious patients compared to nondelirious preoperatively and at POD2, respectively (P < .05). Following biological and methodological criteria, 12 biomarker candidates (Tukey's fold change [|tFC|] >1.4, Benjamini-Hochberg [BH]-P < .01) were selected for ELLA multiplex validation. Statistical analyses of model fit resulted in the combination of age, sex, and 3 proteins (angiopoietin-2; C-C motif chemokine 5; and metalloproteinase inhibitor 1; area under the curve [AUC] = 0.829) as the best performing predictive model for delirium. Analyses of pathways showed that delirium-associated proteins are involved in inflammation, glial dysfunction, vascularization, and hemostasis.

CONCLUSIONS: Our results support the identification of patients at higher risk of developing delirium after cardiac surgery using a multivariable model that combines demographic and physiological features, also bringing light to the role of immune and vascular dysregulation as underlying mechanisms.

PMID:39774401 | DOI:10.1213/ANE.0000000000007293

PLoS Comput Biol. 2025 Jan 7;21(1):e1012736. doi: 10.1371/journal.pcbi.1012736. Online ahead of print.

ABSTRACT

The denitrifying bacterium Thauera sp. MZ1T, a common member of microbial communities in wastewater treatment facilities, can produce different compounds from a range of carbon (C) and nitrogen (N) sources under aerobic and anaerobic conditions. In these different conditions, Thauera modifies its metabolism to produce different compounds that influence the microbial community. In particular, Thauera sp. MZ1T produces different exopolysaccharides with floc-forming properties, impacting the physical disposition of wastewater consortia and the efficiency of nutrient assimilation by the microbial community. Under N-limiting conditions, Thauera sp. MZ1T decreases its growth rate and accelerates the accumulation of polyhydroxyalkanoate-related (PHA) compounds including polyhydroxybutyrate (PHB), which plays a fundamental role as C and energy storage in this β-proteobacterium. However, the metabolic mechanisms employed by Thauera sp. MZ1T to assimilate and catabolize many of the different C and N sources under aerobic and anaerobic conditions remain unknown. Systems biology approaches such as genome-scale metabolic modeling have been successfully used to unveil complex metabolic mechanisms for various microorganisms. Here, we developed a comprehensive metabolic model (M-model) for Thauera sp. MZ1T (iThauera861), consisting of 1,744 metabolites, 2,384 reactions, and 861 genes. We validated the model experimentally using over 70 different C and N sources under both aerobic and anaerobic conditions. iThauera861 achieved a prediction accuracy of 95% for growth on various C and N sources and close to 85% for assimilation of aromatic compounds under denitrifying conditions. The M-model was subsequently deployed to determine the effects of substrates, oxygen presence, and the C:N ratio on the production of PHB and exopolysaccharides (EPS), showing the highest polymer yields are achieved with nucleotides and amino acids under aerobic conditions. This comprehensive M-model will help reveal the metabolic processes by which this ubiquitous species influences communities in wastewater treatment systems and natural environments.

PMID:39774301 | DOI:10.1371/journal.pcbi.1012736

J Clin Sleep Med. 2025 Jan 7. doi: 10.5664/jcsm.11524. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Onera Health has developed the first wireless, patch-based, type-II PSG system, the Onera Sleep Test System (STS), to allow studies to be performed unattended at the patient's home or in any bed at a medical facility. The goal of this multicenter study was to validate data collected from the patch-based PSG to a traditional PSG for sleep staging and AHI.

METHODS: Simultaneous traditional PSG and patch-based PSG study data were obtained in a sleep laboratory from 206 participants with a suspected sleep disorder recruited from 7 clinical sites. Blinded, randomized scoring of the traditional PSG and patch-based PSG recordings was completed according to The AASM Manual for the Scoring of Sleep and Associated Events, version 2.6 criteria by three independent scorers.

RESULTS: Concordance correlation coefficients were high between the patch-based device and traditional PSG across essential sleep and respiratory variables - TST (0.87); Wake (0.84); NREM (0.80); N1 (0.72); N2 (0.71); N3 (0.64); REM (0.80) and AHI (0.94). There was substantial agreement between epoch sleep staging scored on the patch-based device and traditional PSG (average Cohen's kappa of 0.62 ± 0.13 across all scorers).

CONCLUSIONS: The patch-based type-II PSG had a similar performance on sleep staging and respiratory variables when compared to Traditional PSG, thus making it possible to use the patch-based PSG for a routine PSG study. These results open the possibility of performing unattended PSG studies efficiently and accurately outside the sleep laboratory improving access to high quality sleep assessments for patients with sleep disorders.

CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT05310708.

PMID:39773950 | DOI:10.5664/jcsm.11524

BMC Bioinformatics. 2025 Jan 7;26(1):4. doi: 10.1186/s12859-024-06027-7.

ABSTRACT

In cell line perturbation experiments, a collection of cells is perturbed with external agents and responses such as protein expression measured. Due to cost constraints, only a small fraction of all possible perturbations can be tested in vitro. This has led to the development of computational models that can predict cellular responses to perturbations in silico. A central challenge for these models is to predict the effect of new, previously untested perturbations that were not used in the training data. Here we propose causal structural equations for modeling how perturbations effect cells. From this model, we derive two estimators for predicting responses: a Linear Regression (LR) estimator and a causal structure learning estimator that we term Causal Structure Regression (CSR). The CSR estimator requires more assumptions than LR, but can predict the effects of drugs that were not applied in the training data. Next we present Cellbox, a recently proposed system of ordinary differential equations (ODEs) based model that obtained the best prediction performance on a Melanoma cell line perturbation data set (Yuan et al. in Cell Syst 12:128-140, 2021). We derive analytic results that show a close connection between CSR and Cellbox, providing a new causal interpretation for the Cellbox model. We compare LR and CSR/Cellbox in simulations, highlighting the strengths and weaknesses of the two approaches. Finally we compare the performance of LR and CSR/Cellbox on the benchmark Melanoma data set. We find that the LR model has comparable or slightly better performance than Cellbox.

PMID:39773352 | DOI:10.1186/s12859-024-06027-7

Sci Transl Med. 2025 Jan 8;17(780):eadl2103. doi: 10.1126/scitranslmed.adl2103. Epub 2025 Jan 8.

ABSTRACT

Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached the market. We found that, with the exception of compound SCH79797, antibiotic resistance generally readily evolves in Staphylococcus aureus. Cross-resistance was detected between such candidates and antibiotics currently in clinical use, including vancomycin, daptomycin, and the promising antibiotic candidate teixobactin. These patterns were driven by overlapping molecular mechanisms through mutations in regulatory systems. In particular, teixobactin-resistant bacteria displayed clinically relevant multidrug resistance and retained their virulence in an invertebrate infection model, raising concerns. More generally, we demonstrate that putative resistance mutations against candidate antibiotics are already present in natural bacterial populations. Therefore, antibiotic resistance in nature may evolve readily from the selection of preexisting genetic variants. Our work highlights the importance of predicting future evolution of resistance to antibiotic candidates at an early stage of drug development.

PMID:39772773 | DOI:10.1126/scitranslmed.adl2103

J Proteome Res. 2025 Jan 7. doi: 10.1021/acs.jproteome.4c00160. Online ahead of print.

ABSTRACT

Immunoprecipitation coupled to tandem mass spectrometry (IP-MS/MS) methods is often used to identify protein-protein interactions (PPIs). While these approaches are prone to false positive identifications through contamination and antibody nonspecific binding, their results can be filtered using negative controls and computational modeling. However, such filtering does not effectively detect false-positive interactions when IP-MS/MS is performed on human plasma samples. Therein, proteins cannot be overexpressed or inhibited, and existing modeling algorithms are not adapted for execution without such controls. Hence, we introduce MAGPIE, a novel machine learning-based approach for identifying PPIs in human plasma using IP-MS/MS, which leverages negative controls that include antibodies targeting proteins not expected to be present in human plasma. A set of negative controls used for false positive interaction modeling is first constructed. MAGPIE then assesses the reliability of PPIs detected in IP-MS/MS experiments using antibodies that target known plasma proteins. When applied to five IP-MS/MS experiments as a proof of concept, our algorithm identified 68 PPIs with an FDR of 20.77%. MAGPIE significantly outperformed a state-of-the-art PPI discovery tool and identified known and predicted PPIs. Our approach provides an unprecedented ability to detect human plasma PPIs, which enables a better understanding of biological processes in plasma.

PMID:39772751 | DOI:10.1021/acs.jproteome.4c00160

ACS Appl Mater Interfaces. 2025 Jan 7. doi: 10.1021/acsami.4c17482. Online ahead of print.

ABSTRACT

Enveloped viruses, such as flaviviruses and coronaviruses, are pathogens of significant medical concern that cause severe infections in humans. Some photosensitizers are known to possess virucidal activity against enveloped viruses, targeting their lipid bilayer. Here we report a series of halogenated difluoroboron-dipyrromethene (BODIPYs) photosensitizers with strong virus-inactivating activity. Our structure-activity relationship analysis revealed that BODIPY scaffolds with a heavy halogen atom demonstrate significant efficacy against both tick-borne encephalitis virus (TBEV; Flaviviridae family) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Coronaviridae family) along with high singlet oxygen quantum yields. Moreover, select compounds also inactivated other enveloped viruses, such as herpes simplex virus type 1 and monkeypox virus. The nature and length of the alkyl side chain notably influenced the virus-inactivating activity of BODIPY molecules. Furthermore, molecular dynamics studies highlighted the critical importance of the positioning of the chromophore moiety within the lipid bilayer. As membrane-targeting photosensitizers, BODIPYs interact directly with virus particles, causing damage to the viral envelope membranes. Thus, TBEV pretreated with BODIPY was completely noninfective for lab mice. Consequently, BODIPY-based photosensitizers hold potential either as broad-spectrum virus-inactivating antivirals against a variety of phylogenetically unrelated enveloped viruses or as potent inactivators of viruses for the development of vaccines for preventing life-threatening emerging viral diseases.

PMID:39772406 | DOI:10.1021/acsami.4c17482

STAR Protoc. 2025 Jan 7;6(1):103517. doi: 10.1016/j.xpro.2024.103517. Online ahead of print.

ABSTRACT

Recently, studies have emerged exploring the potential application of fecal microbiota transplantation (FMT) in pre-clinical settings. Here, we present a protocol for FMT for mice housed in a specific pathogen-free (SPF) facility. We describe steps for sample collection, microaerophilic processing of freshly collected fecal pellets, and administration through oral gavage. We then detail procedures for the engraftment of the bacterial community. This protocol focuses on age- and gender-matched, healthy donor mice using a mobile and cost-effective alternative to an anoxic cabinet.

PMID:39772388 | DOI:10.1016/j.xpro.2024.103517

Viruses. 2024 Dec 17;16(12):1926. doi: 10.3390/v16121926.

ABSTRACT

This study investigated a library of known and novel glycyrrhizic acid (GL) conjugates with amino acids and dipeptide esters, as inhibitors of the DENV NS2B-NS3 protease. We utilized docking algorithms to evaluate the interactions of these GL derivatives with key residues (His51, Asp75, Ser135, and Gly153) within 10 Å of the DENV-2 NS2B-NS3 protease binding pocket (PDB ID: 2FOM). It was found that compounds 11 and 17 exhibited unique binding patterns, forming hydrogen bonds with Asp75, Tyr150, and Gly153. Based on the molecular docking data, conjugates 11 with L-glutamic acid dimethyl ester, 17 with β-alanine ethyl ester, and 19 with aminoethantic acid methyl ester were further demonstrated as potent inhibitors of DENV-2 NS3 protease, with IC50 values below 1 μM, using NS3-mediated cleavage assay. Compound 11 was the most potent, with EC50 values of 0.034 μM for infectivity, 0.042 μM for virus yield, and a selective index over 2000, aligning with its strong NS3 protease inhibition. Compound 17 exhibited better NS3 protease inhibition than compound 19 but showed weaker effects on infectivity and virus yield. While all compounds strongly inhibited viral infectivity post-entry, compound 19 also blocked viral entry. This study provided valuable insights into the interactions between active GL derivatives and DENV-2 NS2B-NS3 protease, offering a comprehensive framework for identifying lead compounds for further drug optimization and design as NS2B-NS3 protease inhibitors against DENV.

PMID:39772233 | DOI:10.3390/v16121926

Viruses. 2024 Dec 5;16(12):1885. doi: 10.3390/v16121885.

ABSTRACT

Viromics studies are allowing us to understand not only the enormous diversity of the virosphere, but also the potential threat posed by the emerging viruses. Regarding the latter, the main concern lies in monitoring the presence of RNA viruses, but the zoonotic potential of some DNA viruses, on which we have focused in the present study, should also be highlighted. For this purpose, we analyzed 160 fecal samples from 14 species of small terrestrial mammals, 9 of them belonging to the order Rodentia. This allowed us to identify a total of 25 complete or near-complete genomes belonging to the families Papillomaviridae, Polyomaviridae, Adenoviridae, Circoviridae, and Genomoviridae, 18 of which could be considered new species or types. Our results provide a significant increase in the number of complete genomes of DNA viruses of European origin with zoonotic potential in databases, which are at present under-represented compared to RNA viruses. In addition, the characterization of whole genomes is of relevance for the further study of the evolutionary forces governing virus adaptation, such as recombination, which may play an important role in cross-species transmission.

PMID:39772193 | DOI:10.3390/v16121885

Vaccines (Basel). 2024 Dec 6;12(12):1377. doi: 10.3390/vaccines12121377.

ABSTRACT

Background/Objectives: Poxviruses are large DNA viruses that replicate in the host cytoplasm without a nuclear phase. As vaccine vectors, they can package and express large recombinant cassettes from different positions of their genomic core region. We present a comparison between wildtype modified vaccinia Ankara (MVA) and isolate CR19, which has significantly expanded inverted terminal repeats (ITRs). With this expansion, a site in wildtype MVA, called deletion site (DS) IV, has been duplicated at both ends of the genome and now occupies an almost central position in the newly formed ITRs. Methods: We inserted various reporter genes into this site and found that the ITRs can be used for transgene expression. However, ITRs are genomic structures that can rapidly adapt to selective pressure through transient duplication and contraction. To test the potential utility of insertions into viral telomers, we inserted a factor from the cellular innate immune system that interferes with viral replication as an example of a difficult transgene. Results: A site almost in the centre of the ITRs can be used for transgene expression, and both sides are mirrored into identical copies. The example of a challenging transgene, tetherin, proved to be surprisingly efficient in selecting candidate vectors against the large background of parental viruses. Conclusions: Insertion of transgenes into ITRs automatically doubles the gene doses. The functionalisation of viruses with tetherin may accelerate the identification and generation of recombinant vectors for personalised medicine and pandemic preparedness.

PMID:39772039 | DOI:10.3390/vaccines12121377

Polymers (Basel). 2024 Dec 21;16(24):3573. doi: 10.3390/polym16243573.

ABSTRACT

Polyurethane materials, widely used in indoor environments, occasionally exhibit unpleasant odors. An important source of polyurethane odorants is polyether polyols. Previous studies identified odorous 2-ethyldimethyl-1,3,6-trioxocanes in polyurethane materials and polyols but did not investigate the odor activity of the individual isomers. In the present work, an isomer mixture of the precursor dipropylene glycol was fractionated through preparative high-performance liquid chromatography. After the conversion to the corresponding trioxocanes, gas chromatography-olfactometry analyses revealed that just one positional isomer, namely 2-ethyl-4,7-dimethyl-1,3,6-trioxocane, was odor active. Moreover, we observed clear differences in the odor threshold concentrations among its stereoisomers. Only two out of eight isomers displayed an odor, both with an earthy smell and one being approximately 60 times more potent than the other. These insights contribute to a better understanding of polyurethane odor on a molecular level and provide a basis for effective odor control.

PMID:39771426 | DOI:10.3390/polym16243573

Plants (Basel). 2024 Dec 18;13(24):3536. doi: 10.3390/plants13243536.

ABSTRACT

Medicinal plants have long played a crucial role in healthcare systems, but limited genomic information on these species has impeded the integration of modern biological technologies into medicinal plant research. In this study, we selected nine common medicinal plants, each belonging to a different plant family, including Sarcandra glabra (Chloranthaceae), Nekemias grossedentata (Vitaceae), Uraria crinita (Fabaceae), Gynostemma pentaphyllum (Cucurbitaceae), Reynoutria japonica (Polygonaceae), Pseudostellaria heterophylla (Caryophyllaceae), Morinda officinalis (Rubiaceae), Vitex rotundifolia (Lamiaceae), and Gynura formosana (Asteraceae), to estimate their genome sizes and conduct preliminary genomic surveys. The estimated genome sizes by flow cytometry were 3.66 Gb, 0.65 Gb, 0.58 Gb, 1.02 Gb, 3.96 Gb, 2.99 Gb, 0.43 Gb, 0.78 Gb, and 7.27 Gb, respectively. The genome sizes of M. officinalis, R. japonica, and G. pentaphyllum have been previously reported. Comparative analyses suggest that variations in genome size may arise due to differences in measurement methods and sample sources. Therefore, employing multiple approaches to assess genome size is necessary to provide more reliable information for further genomic research. Based on the genome survey, species with considerable genome size variation or polyploidy, such as G. pentaphyllum, should undergo a ploidy analysis in conjunction with population genomics studies to elucidate the development of the diversified genome size. Additionally, a genome survey of U. crinita, a medicinal plant with a relatively small genome size (509.08 Mb) and of considerable interest in southern China, revealed a low heterozygosity rate (0.382%) and moderate repeat content (51.24%). Given the limited research costs, this species represents a suitable candidate for further genomic studies on Leguminous medicinal plants characteristic of southern China. This foundational genomic information will serve as a critical reference for the sustainable development and utilization of these medicinal plants.

PMID:39771235 | DOI:10.3390/plants13243536

Toxics. 2024 Dec 23;12(12):938. doi: 10.3390/toxics12120938.

ABSTRACT

This review delves into the impact of benzo(a)pyrene (B(a)P), which is a toxic and pervasive polycyclic aromatic hydrocarbon (PAH) and known carcinogen, on the human health risk from a gut microbiome perspective. We retrieved the relevant articles on each PAH and summarized the reporting to date, with a particular focus on benzo(a)pyrene, which has been reported to have a high risk of gut microbiome-related harm. B(a)P exposure can compromise the homeostasis of the gut microbiota, leading to dysbiosis, a state of microbial imbalance. The consequences of B(a)P-induced gut dysbiosis can be far-reaching, potentially contributing to inflammation, metabolic disorders, and an increased risk of various diseases. Additionally, due to the strong coupling between B(a)P and microparticles, the toxicity of B(a)P may be further compounded by its reaction with strong gut disruptors such as micro-/nanoplastics, which have recently become a serious environmental concern. This review summarizes current research on the impact of B(a)P on the gut microbiome, highlighting the intricate relationship between environmental exposure, gut health, and human disease. Further research is necessary to elucidate the underlying mechanisms and develop effective strategies to mitigate the adverse health effects of B(a)P exposure.

PMID:39771153 | DOI:10.3390/toxics12120938

Toxics. 2024 Nov 27;12(12):860. doi: 10.3390/toxics12120860.

ABSTRACT

Copper mining drives economic growth, with the global demand expected to reach 120 million metric tons annually by 2050. However, mining produces tailings containing heavy metals (HMs), which poses environmental risks. This study investigated the efficacy of phytoremediation (Phy) combined with electrokinetic treatment (EKT) to increase metal uptake in Carpobrotus aequilaterus grown in tailings from the Metropolitan Region of Chile. The plants were exposed to varying voltages and treatment durations. In the control (no EKT), the root metal contents were Fe (1008.41 mg/kg) > Cu (176.38 mg/kg) > Mn (103.73 mg/kg) > Zn (30.26 mg/kg), whereas in the shoots, the order was Mn (48.69 mg/kg) > Cu (21.14 mg/kg) > Zn (17.67 mg/kg) > Fe (27.32 mg/kg). The optimal EKT (15 V for 8 h) significantly increased metal uptake, with roots accumulating Fe (5997.24 mg kg-1) > Mn (672 mg kg-1) > Cu (547.68 mg kg-1) > Zn (90.99 mg kg-1), whereas shoots contained Fe (1717.95 mg kg-1) > Mn (930 mg kg-1) > Cu (219.47 mg kg-1) > Zn (58.48 mg kg-1). Although EKT enhanced plant growth and biomass, higher voltages stressed the plants. Longer treatments were more effective, suggesting that EK-Phy is a promising method for remediating metal-contaminated tailings.

PMID:39771075 | DOI:10.3390/toxics12120860

Microorganisms. 2024 Dec 2;12(12):2475. doi: 10.3390/microorganisms12122475.

ABSTRACT

Wastewater-based surveillance (WBS) is a proven tool for monitoring population-level infection events. Wastewater contains high concentrations of inhibitors, which contaminate the total nucleic acids (TNA) extracted from these samples. We found that TNA extracts from raw influent of Berlin wastewater treatment plants contained highly variable amounts of inhibitors that impaired molecular analyses like dPCR and next-generation sequencing (NGS). By using dilutions, we were able to detect inhibitory effects. To enhance WBS sensitivity and stability, we applied a combination of PCR inhibitor removal and TNA dilution (PIR+D). This approach led to a 26-fold increase in measured SARS-CoV-2 concentrations, practically reducing the detection limit. Additionally, we observed a substantial increase in the stability of the time series. We define suitable stability as a mean absolute error (MAE) below 0.1 log10 copies/L and a geometric mean relative absolute error (GMRAE) below 26%. Using PIR+D, the MAE could be reduced from 0.219 to 0.097 and the GMRAE from 65.5% to 26.0%, and even further in real-world WBS. Furthermore, PIR+D improved SARS-CoV-2 genome alignment and coverage in amplicon-based NGS for low to medium concentrations. In conclusion, we strongly recommend both the monitoring and removal of inhibitors from samples for WBS.

PMID:39770678 | DOI:10.3390/microorganisms12122475

Microorganisms. 2024 Nov 28;12(12):2449. doi: 10.3390/microorganisms12122449.

ABSTRACT

Arctic char is a top predator in Arctic waters and is threatened by mercury pollution in the context of changing climate. Gill microbiota is directly exposed to environmental xenobiotics and play a central role in immunity and fitness. Surprisingly, there is a lack of literature studying the effect of mercury on gill microbiota. To fill this knowledge gap, our primary goal was to measure to what extent gill exposure to mercury may alter gill microbiota activity in Arctic char. Specifically, we calculated the correlation between the taxonomic distribution of gill-associated bacterial symbiont activity and total mercury concentration in livers and muscles in wild populations of Arctic char in the Canadian Arctic. Our results showed that total mercury concentrations in tissues were higher in Ekaluktutiak (Nunavut) than in the other sites in Nunavik. Proteobacteria was the main phylum correlated to mercury concentration in both tissues, followed by Bacteroidetes and Cyanobacteria. In the most contaminated sites, Aeromonas and Pseudomonas (Proteobacteria) were predominant, while mercury concentration negatively correlated with Photobacterium (Proteobacteria) or Cerasicoccus (Verrucomicrobia). In summary, we found that mercury contamination correlates with active gill microbiota composition, with potential implications of strains in modulating mercury toxicity, making them interesting for future biomarker studies.

PMID:39770652 | DOI:10.3390/microorganisms12122449

Pharmaceuticals (Basel). 2024 Dec 22;17(12):1736. doi: 10.3390/ph17121736.

ABSTRACT

Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. Methods: For this reason, we constructed a disease-protein-drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition. Apart from the amyloidogenic proteins that self-assemble into fibrils, we also included other co-deposited proteins found in amyloid deposits. Results: In this work, protein-protein, protein-drug, and disease-drug associations were collected to create a heterogenous network. Through disease-based and drug-based analyses, we highlighted commonalities between diseases and proposed an approved drug with prospects of repurposing. Conclusions: The identified disease associations and drug candidates are proposed for further study that will potentially help treat diseases associated with amyloid deposition.

PMID:39770578 | DOI:10.3390/ph17121736

Int J Mol Sci. 2024 Dec 18;25(24):13540. doi: 10.3390/ijms252413540.

ABSTRACT

Gene transfection is a fundamental technique in the fields of biological research and therapeutic innovation. Due to their biocompatibility and membrane-mimetic properties, lipid vectors serve as essential tools in transfection. The successful delivery of genetic material into the cytoplasm is contingent upon the fusion of the vector and cellular membranes, which enables hydrophilic polynucleic acids to traverse the hydrophobic barriers of two intervening membranes. This review examines the critical role of membrane fusion in lipofection efficiency, with a particular focus on the molecular mechanisms that govern lipoplex-membrane interactions. This analysis will examine the key challenges inherent to the fusion process, from achieving initial membrane proximity to facilitating final content release through membrane remodeling. In contrast to viral vectors, which utilize specialized fusion proteins, lipid vectors necessitate a strategic formulation and environmental optimization to enhance their fusogenicity. This review discusses recent advances in vector design and fusion-promoting strategies, emphasizing their potential to improve gene delivery yield. It highlights the importance of understanding lipoplex-membrane fusion mechanisms for developing next-generation delivery systems and emphasizes the need for continued fundamental research to advance lipid-mediated transfection technology.

PMID:39769303 | DOI:10.3390/ijms252413540