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IScience May 2024In , DNA replication, and asynchronous nuclear divisions precede cytokinesis during intraerythrocytic schizogony. Regulation of nuclear division through the import of...
In , DNA replication, and asynchronous nuclear divisions precede cytokinesis during intraerythrocytic schizogony. Regulation of nuclear division through the import of serum components was largely unknown. At the trophozoite stage, ribosomal protein P2 (PfP2) is exported to the infected erythrocyte (IE) cytosol and the surface as a denaturation-resistant tetramer. The inaccessibility of the IE surface exposed PfP2 to its bona fide ligand led to the arrest of nuclear division. Here, we show that at the onset of schizogony, denaturation-resistant PfP2 tetramer on the IE surface imports fatty acids (FAs). Blockage of import reversibly arrested parasite schizogony. In Met--Met mediated denaturation resistant PfP2 tetramer, the Cys-Cys redox switch regulates the binding and release of FAs based on oxidized/reduced state of disulfide linkages. This mechanistic insight of FAs import through PfP2 tetramer reveals a unique regulation of nuclear division at the onset of schizogony.
PubMed: 38726364
DOI: 10.1016/j.isci.2024.109760 -
The Journal of Biological Chemistry May 2024In Escherichia coli, the master transcription regulator catabolite repressor activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is...
In Escherichia coli, the master transcription regulator catabolite repressor activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that the E. coli enzyme fructose-1-kinase (FruK) can carry out its "reverse" reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a ΔfruK strain and fruK complementation show that FruK has a broader role in metabolism than fructose catabolism. Since fruK itself is repressed by Cra, these newly-reported events add layers to the dynamic regulation of E. coli's central metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK.
PubMed: 38723750
DOI: 10.1016/j.jbc.2024.107352 -
BMC Oral Health May 2024To investigate the effect of concentrated growth factor (CGF) combined with sodium hyaluronate (SH) on temporomandibular joint osteoarthritis (TMJOA). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the effect of concentrated growth factor (CGF) combined with sodium hyaluronate (SH) on temporomandibular joint osteoarthritis (TMJOA).
METHODS
Sixty patients with TMJOA who were diagnosed by cone-beam computed tomography (CBCT) between March 2020 and March 2023 at the Stomatological Hospital of Xi'an Jiaotong University were randomly divided into a control group (n = 30) and an experimental group (n = 30). The patients in the experimental group were treated with CGF + SH, and those in the control group were treated with SH only. The visual analogue scale (VAS) score indicating pain in the temporomandibular joint (TMJ) area; the Helkimo Clinical Dysfunction Index (Di); and changes in condylar CBCT at the first visit and 2 weeks, 3 months and 6 months after treatment were recorded. The CBCT data of the patients in the experimental and control groups were collected, and the three-dimensional CBCT image sequences were imported into Mimics Medical 19.0 software in DICOM format for condylar reconstruction.
RESULTS
The VAS scores at 2 weeks, 3 months and 6 months after treatment were significantly lower in the experimental group than in the control group (P < 0.05), and the pain in the experimental group was significantly relieved. The Di was significantly lower in the experimental group than in the control group (P < 0.05), and the clinical function of the TMJ improved. After treatment, the CBCT score was significantly lower in the experimental group than in the control group (P < 0.05), and the condylar bone cortex was obviously repaired. Observation of the condylar bone cortex by three-dimensional reconstruction showed the same results as those obtained by CBCT.
CONCLUSION
CGF combined with SH is effective in the treatment of TMJOA and can improve muscle pain, TMJ pain, Impaired TMJ function, Impaired range of movement, Pain on movement of the mandible and promote bone repair.
THE REGISTRATION NUMBER (TRN)
ChiCTR2400082712.
THE DATE OF REGISTRATION
April 5, 2024.
Topics: Humans; Hyaluronic Acid; Female; Male; Osteoarthritis; Cone-Beam Computed Tomography; Temporomandibular Joint Disorders; Adult; Middle Aged; Pain Measurement; Intercellular Signaling Peptides and Proteins; Treatment Outcome
PubMed: 38720327
DOI: 10.1186/s12903-024-04258-x -
PloS One 2024Preeclampsia (PE) is a severe complication of unclear pathogenesis associated with pregnancy. This research aimed to elucidate the properties of immune cell infiltration...
OBJECTIVE
Preeclampsia (PE) is a severe complication of unclear pathogenesis associated with pregnancy. This research aimed to elucidate the properties of immune cell infiltration and potential biomarkers of PE based on bioinformatics analysis.
MATERIALS AND METHODS
Two PE datasets were imported from the Gene ExpressioOmnibus (GEO) and screened to identify differentially expressed genes (DEGs). Significant module genes were identified by weighted gene co-expression network analysis (WGCNA). DEGs that interacted with key module genes (GLu-DEGs) were analyzed further by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The diagnostic value of the genes was assessed using receiver operating characteristic (ROC) curves and protein-protein interaction (PPI) networks were constructed using GeneMANIA, and GSVA analysis was performed using the MSigDB database. Immune cell infiltration was analyzed using the TISIDB database, and StarBase and Cytoscape were used to construct an RBP-mRNA network. The identified hub genes were validated in two independent datasets. For further confirmation, placental tissue from healthy pregnant women and women with PE were collected and analyzed using both RT-qPCR and immunohistochemistry.
RESULTS
A total of seven GLu-DEGs were obtained and were found to be involved in pathways associated with the transport of sulfur compounds, PPAR signaling, and energy metabolism, shown by GO and KEGG analyses. GSVA indicated significant increases in adipocytokine signaling. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) indicated that the levels of activated B cells and T follicular helper cells were significantly increased in the PE group and were negatively correlated with GLu-DEGs, suggesting their potential importance.
CONCLUSION
In summary, the results showed a correlation between glutamine metabolism and immune cells, providing new insights into the understandingPE pathogenesis and furnishing evidence for future advances in the treatment of this disease.
Topics: Humans; Pre-Eclampsia; Female; Pregnancy; Protein Interaction Maps; Glutamine; Gene Regulatory Networks; Computational Biology; Gene Ontology; Gene Expression Profiling; Adult; Placenta
PubMed: 38718074
DOI: 10.1371/journal.pone.0303471 -
Journal of Bacteriology May 2024A new study by Nies et al. (J Bacteriol 206:e00080-24, 2024, https://doi.org/10.1128/jb.00080-24) provides a rich, quantitative data set of zinc accumulation by cells of...
A new study by Nies et al. (J Bacteriol 206:e00080-24, 2024, https://doi.org/10.1128/jb.00080-24) provides a rich, quantitative data set of zinc accumulation by cells of , including of mutant bacterial strains lacking import or efflux genes, and comparison of zinc accumulation by cells previously starved of metal with those of zinc-replete cells. The data surprisingly demonstrate the concomitant activity of both active metal import and metal efflux systems. They present a flow equilibrium model to describe zinc homeostasis in bacteria.
Topics: Homeostasis; Cupriavidus; Biological Transport; Zinc; Bacterial Proteins; Gene Expression Regulation, Bacterial; Metals
PubMed: 38712925
DOI: 10.1128/jb.00146-24 -
BioRxiv : the Preprint Server For... Apr 2024Primary microRNA (pri-miRNA) transcripts are processed by the Microprocessor, a protein complex that includes the ribonuclease Drosha and its RNA binding partner...
Primary microRNA (pri-miRNA) transcripts are processed by the Microprocessor, a protein complex that includes the ribonuclease Drosha and its RNA binding partner DGCR8/Pasha. We developed a live, whole animal, fluorescence-based sensor that reliably monitors pri-miRNA processing with high sensitivity in . Through a forward genetic selection for alleles that desilence the sensor, we identified a mutation in the conserved G residue adjacent to the namesake W residue of Pasha's WW domain. Using genome editing we also mutated the W residue and reveal that both the G and W residue are required for dimerization of Pasha and proper assembly of the Microprocessor. Surprisingly, we find that the WW domain also facilitates nuclear localization of Pasha, which in turn promotes nuclear import or retention of Drosha. Furthermore, depletion of Pasha or Drosha causes both components of the Microprocessor to mislocalize to the cytoplasm. Thus, Pasha and Drosha mutually regulate each other's spatial expression in .
PubMed: 38712061
DOI: 10.1101/2024.04.23.590772 -
BioRxiv : the Preprint Server For... Apr 2024(.), the leading cause of bacterial sexually transmitted infections, employs a type III secretion system (T3SS) to translocate two classes of effectors, inclusion...
(.), the leading cause of bacterial sexually transmitted infections, employs a type III secretion system (T3SS) to translocate two classes of effectors, inclusion membrane proteins and conventional T3SS (cT3SS) effectors, into the host cell to counter host defense mechanisms. Here we employed three assays to directly evaluate secretion during infection, validating secretion for 23 cT3SS effectors. As bioinformatic analyses have been largely unrevealing, we conducted affinity purification-mass spectrometry to identify host targets and gain insights into the functions of these effectors, identifying high confidence interacting partners for 21 cT3SS effectors. We demonstrate that CebN localizes to the nuclear envelope in infected and bystander cells where it interacts with multiple nucleoporins and Rae1, blocking STAT1 nuclear import following IFN-γ stimulation. By building a cT3SS effector-host interactome, we have identified novel pathways that are targeted during bacterial infection and have begun to address how effectors combat cell autonomous immunity.
PubMed: 38712050
DOI: 10.1101/2024.04.25.587017 -
Frontiers in Veterinary Science 2024The increased fish consumption by the growing human population in the world translates into an increase in fish waste. The reintroduction of these fish by-products into...
The increased fish consumption by the growing human population in the world translates into an increase in fish waste. The reintroduction of these fish by-products into food and feed chains presents economic benefits and contributes to counteracting their negative environmental impact. Under this context, the present study aimed to evaluate the effects of the dietary inclusion of fish hydrolysate and oil obtained from fish waste (experimental diet) in substitution of shrimp hydrolysate and salmon oil (control diet) mainly imported from third countries on palatability, apparent total tract digestibility, fecal characteristics and metabolites, blood fatty acid profile, flatulence, and coat quality of adult dogs. A two-bowl test was performed to evaluate palatability by the pairwise comparison between the two diets. A feeding trial was conducted according to a crossover design with two diets (control and experimental diets), six adult Beagle dogs per diet, and two periods of 6 weeks each. The replacement of shrimp hydrolysate and salmon oil with fish hydrolysate and oil did not affect the first diet approach and taste, as well as the intake ratio. Generally, the digestibility of dry matter, nutrients, and energy was not affected by diet, but the intake of digestible crude protein (CP) and ether extract was higher, respectively, with the control and the experimental diet. The higher intake of eicosapentaenoic acid and docosahexaenoic acid with the experimental diet was reflected in a higher content of these long-chain polyunsaturated fatty acids and the omega-3 index of red blood cells, but it did not affect coat quality. The significantly higher intake of digestible CP with the control diet might have contributed to the higher fecal ammonia-N and valerate concentrations. Daily fecal output and characteristics were similar between diets. Overall, results suggest that fish hydrolysate and oil from the agrifood industry might constitute sustainable functional ingredients for dog feeding while adding value for wild fisheries, aquaculture, and fish farming under a circular economy approach and reducing dependence on imports from third countries with a high carbon footprint.
PubMed: 38711535
DOI: 10.3389/fvets.2024.1372023 -
ELife May 2024Bacteria utilize various strategies to prevent internal dehydration during hypertonic stress. A common approach to countering the effects of the stress is to import...
Bacteria utilize various strategies to prevent internal dehydration during hypertonic stress. A common approach to countering the effects of the stress is to import compatible solutes such as glycine betaine, leading to simultaneous passive water fluxes following the osmotic gradient. OpuA from is a type I ABC-importer that uses two substrate-binding domains (SBDs) to capture extracellular glycine betaine and deliver the substrate to the transmembrane domains for subsequent transport. OpuA senses osmotic stress via changes in the internal ionic strength and is furthermore regulated by the 2nd messenger cyclic-di-AMP. We now show, by means of solution-based single-molecule FRET and analysis with multi-parameter photon-by-photon hidden Markov modeling, that the SBDs transiently interact in an ionic strength-dependent manner. The smFRET data are in accordance with the apparent cooperativity in transport and supported by new cryo-EM data of OpuA. We propose that the physical interactions between SBDs and cooperativity in substrate delivery are part of the transport mechanism.
Topics: ATP-Binding Cassette Transporters; Bacterial Proteins; Betaine; Cryoelectron Microscopy; Fluorescence Resonance Energy Transfer; Lactococcus lactis; Osmolar Concentration; Osmoregulation; Protein Binding; Protein Domains; Single Molecule Imaging
PubMed: 38695350
DOI: 10.7554/eLife.90996 -
Scientific Reports Apr 2024Mitochondria, the powerhouse and the vital signaling hub of the cell, participate in a variety of biological processes, such as apoptosis, redox responses, cell...
Mitochondria, the powerhouse and the vital signaling hub of the cell, participate in a variety of biological processes, such as apoptosis, redox responses, cell senescence, autophagy, and iron homeostasis. Mitochondria form a mostly tubular network, made up of an outer and a cristeae-forming inner membrane. The network undergoes dynamic fusion and fission that change its morphological structure according to the functional needs. Approximately 1500 mitochondrial proteins encoded by nuclear genome plus over 10 proteins encoded by mitochondrial DNA are folded and assembled in the mitochondria under a high-fidelity control system. These proteins are involved in oxidative phosphorylation, metabolism, network and cristae dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance. This Collection gathers original research that advances our understanding of the monitoring techniques and pathophysiological significance of mitochondrial dynamics in health and disease.
Topics: Mitochondrial Dynamics; Humans; Mitochondria; Animals
PubMed: 38688939
DOI: 10.1038/s41598-024-59998-1