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Stem Cell Research Jun 2024Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder that typically presents in infancy as hypoplastic anemia and developmental...
Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder that typically presents in infancy as hypoplastic anemia and developmental abnormalities in approximately 50% of cases. DBAS is caused by haploinsufficiency in one of 24 ribosomal protein genes, with RPS19 mutations accounting for 25% of cases. We generated iPSC lines from two patients with different heterozygous RPS19 mutations (c.191T > C and c.184C > T) and isogenic lines in which the mutations were corrected by Cas9-mediated homology directed repair.
PubMed: 38908299
DOI: 10.1016/j.scr.2024.103479 -
Microbiome Jun 2024The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal...
BACKGROUND
The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown.
RESULTS
A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated.
CONCLUSION
Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Dysbiosis; Gastrointestinal Microbiome; Inflammasomes; Mice; Rats; Hyperuricemia; Male; Disease Models, Animal; Kidney; Mice, Knockout; RNA, Ribosomal, 16S; Fecal Microbiota Transplantation; Urate Oxidase; Mice, Inbred C57BL
PubMed: 38907332
DOI: 10.1186/s40168-024-01826-9 -
Scientific Reports Jun 2024The complete cp genomes of Pedicularis chinensis (GenBank accession number: OQ587614) and Pedicularis kansuensis (GenBank accession number: OQ587613) were sequenced,...
The complete cp genomes of Pedicularis chinensis (GenBank accession number: OQ587614) and Pedicularis kansuensis (GenBank accession number: OQ587613) were sequenced, assembled, and annotated. Their chloroplast (cp) genome lengths were 146,452 bp, and 146,852 bp, respectively; 120 and 116 genes were identified, comprising 75 and 72 protein-coding genes (PCGs), 37 and 36 transfer RNA (tRNA) genes, and 8 and 8 ribosomal RNA (rRNA) genes, for P. chinensis and P. kansuensis, respectively. A simple sequence repeat (SSR) analysis revealed that the repetitive sequences were mainly composed of mononucleotide repeats (A/T motif) and dinucleotide repeats (AT/TA motif). Comparative genomics identified several variant genes (rpl22, rps19, rpl12, ycf1, trnH, psbA, and ndhH) and variant regions (trnS-GGA, trnV-UAC, ndhJ-trnV, ycf4-cemA, ndhE-nhdG, and rpl32-trnL) with a high Pi, indicating the potential to serve as deoxyribo nucleic acid (DNA) barcodes for Pedicularis species identification. The results show that the cp genomes of P. chinensis and P. kansuensis were the same as those of other plants in Pedicularis, with different degrees of AT preference for codons. Large differences in the number of SSRs and the expansion of the inverted repeat (IR) region showed strong variability and interspecific differentiation between these two species and other species represented in the genus Pedicularis. A phylogenetic analysis showed that P. kansuensis had the closest relationship with P. oliveriana, and P. chinensis had the closest relationship with P. aschistorhyncha. These results will facilitate the study of the phylogenetic classification and interspecific evolution of Pedicularis plants.
Topics: Phylogeny; Genome, Chloroplast; Pedicularis; Microsatellite Repeats; RNA, Transfer
PubMed: 38906909
DOI: 10.1038/s41598-024-63815-0 -
Nature Communications Jun 2024Long-term non-progressors (LTNPs) of HIV-1 infection may provide important insights into mechanisms involved in viral control and pathogenesis. Here, our results suggest...
Long-term non-progressors (LTNPs) of HIV-1 infection may provide important insights into mechanisms involved in viral control and pathogenesis. Here, our results suggest that the ribosomal protein lateral stalk subunit P1 (RPLP1) is expressed at higher levels in LTNPs compared to regular progressors (RPs). Functionally, RPLP1 inhibits transcription of clade B HIV-1 strains by occupying the C/EBPβ binding sites in the viral long terminal repeat (LTR). This interaction requires the α-helixes 2 and 4 domains of RPLP1 and is evaded by HIV-1 group M subtype C and group N, O and P strains that do not require C/EBPβ for transcription. We further demonstrate that HIV-1-induced translocation of RPLP1 from the cytoplasm to the nucleus is essential for antiviral activity. Finally, knock-down of RPLP1 promotes reactivation of latent HIV-1 proviruses. Thus, RPLP1 may play a role in the maintenance of HIV-1 latency and resistance to RPLP1 restriction may contribute to the effective spread of clade C HIV-1 strains.
Topics: HIV-1; Humans; Ribosomal Proteins; HIV Long Terminal Repeat; CCAAT-Enhancer-Binding Protein-beta; HIV Infections; Transcription, Genetic; Protein Binding; Virus Latency; Binding Sites; Gene Expression Regulation, Viral; HEK293 Cells; Cell Nucleus
PubMed: 38906865
DOI: 10.1038/s41467-024-49622-1 -
PloS One 2024Homologous recombination is a key process that governs the stability of eukaryotic genomes during DNA replication and repair. Multiple auxiliary factors regulate the...
Homologous recombination is a key process that governs the stability of eukaryotic genomes during DNA replication and repair. Multiple auxiliary factors regulate the choice of homologous recombination pathway in response to different types of replication stress. Using Schizosaccharomyces pombe we have previously suggested the role of DNA translocases Rrp1 and Rrp2, together with Srs2 helicase, in the common synthesis-dependent strand annealing sub-pathway of homologous recombination. Here we show that all three proteins are important for completion of replication after hydroxyurea exposure and provide data comparing the effect of overproduction of Srs2 with Rrp1 and Rrp2. We demonstrate that Srs2 localises to rDNA region and is required for proper replication of rDNA arrays. Upregulation of Srs2 protein levels leads to enhanced replication stress, chromosome instability and viability loss, as previously reported for Rrp1 and Rrp2. Interestingly, our data suggests that dysregulation of Srs2, Rrp1 and Rrp2 protein levels differentially affects checkpoint response: overproduction of Srs2 activates simultaneously DNA damage and replication stress response checkpoints, while cells overproducing Rrp1 mainly launch DNA damage checkpoint. On the other hand, upregulation of Rrp2 primarily leads to replication stress response checkpoint activation. Overall, we propose that Srs2, Rrp1 and Rrp2 have important and at least partially independent functions in the maintenance of distinct difficult to replicate regions of the genome.
Topics: Schizosaccharomyces; Schizosaccharomyces pombe Proteins; DNA Replication; DNA Helicases; DNA Damage; Hydroxyurea; Stress, Physiological; DNA, Ribosomal; Chromosomal Instability
PubMed: 38905307
DOI: 10.1371/journal.pone.0300434 -
PloS One 2024Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T....
Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.
Topics: Treponema pallidum; Humans; Pakistan; Syphilis; Blood Donors; Anti-Bacterial Agents; Drug Resistance, Bacterial; Male; Female; Adult; Macrolides; RNA, Ribosomal, 23S; RNA, Ribosomal, 16S; Middle Aged; Doxycycline; Young Adult
PubMed: 38905249
DOI: 10.1371/journal.pone.0305720 -
PloS One 2024The dung beetle primarily feeds on the feces of herbivorous animals and play a crucial role in ecological processes like material cycles and soil improvement. This study...
The dung beetle primarily feeds on the feces of herbivorous animals and play a crucial role in ecological processes like material cycles and soil improvement. This study aims to explore the diversity and composition of the gut microbiota of Catharsius molossus (a renowned dung beetle originating from China and introduced to multiple countries for its ecological value) and exploring whether these gut microbes are transmitted vertically across generations. Using 16S rRNA and ITS rRNA gene sequencing techniques, we described the diversity and composition of gut microbes in C. molossus from different localities and different developmental stages (Egg, young larvae and old larvae). We discovered that the diversity of gut microbiota of dung beetles varied obviously among different geographical localities and different developmental stages, and we also discussed the potential influencing factors. Interestingly, the microbial community structure within the brood balls is more similar to male dung beetle than to that of females, which is consistent with the observation that the brood ball is constructed by the male dung beetle, with the female laying egg in it at the final step. This unique breeding method facilitates offspring in inheriting microbial communities from both the mother and the father. Initially, the larvae's gut microbiota closely mirrors that of the parental gift in these brood balls. As larvae grow, significant changes occur in their gut microbiota, including an increase in symbiotic bacteria like Lactococcus and Enterococcus. Analysis of the gut bacteria of adult dung beetles across various localities and different developmental stages identified nine core genera in adults, contributing to 67.80% of the total microbial abundance, and 11 core genera in beetles at different developmental stages, accounting for 49.13% of the total. Notably, seven genera were common between these two core groups. Our results suggest that Parental gifts can play a role in the vertical transmission of microbes, and the abundance of probiotics increases with larval development, supporting the hypothesis that "larval feeding behavior occurs in two stages: larvae first feed on parental gifts to acquire necessary microbes, then enrich symbiotic microbiota through consuming their own feces."
Topics: Animals; Coleoptera; Gastrointestinal Microbiome; Female; Male; Larva; RNA, Ribosomal, 16S; Bacteria; Biodiversity; China; Phylogeny
PubMed: 38905245
DOI: 10.1371/journal.pone.0304908 -
Applied Microbiology and Biotechnology Jun 2024Direct ammonia oxidation (Dirammox) might be of great significance to advance the innovation of biological nitrogen removal process in wastewater treatment systems....
Direct ammonia oxidation (Dirammox) might be of great significance to advance the innovation of biological nitrogen removal process in wastewater treatment systems. However, it remains unknown whether Dirammox bacteria can be selectively enriched in activated sludge. In this study, a lab-scale bioreactor was established and operated for 2 months to treat synthetic wastewater with hydroxylamine as a selection pressure. Three Dirammox strains (Alcaligenes aquatilis SDU_AA1, Alcaligenes aquatilis SDU_AA2, and Alcaligenes sp. SDU_A2) were isolated from the activated sludge, and their capability to perform Dirammox process was confirmed. Although these three Dirammox bacteria were undetectable in the seed sludge (0%), their relative abundances rapidly increased after a month of operation, reaching 12.65%, 0.69%, and 0.69% for SDU_A2, SDU_AA1, and SDU_AA2, respectively. Among them, the most dominant Dirammox (SDU_A2) exhibited higher nitrogen removal rate (32.35%) than the other two strains (13.57% of SDU_AA1 and 14.52% of SDU_AA2). Comparative genomic analysis demonstrated that the most dominant Dirammox bacterium (SDU_A2) possesses fewer complete metabolic modules compared to the other two less abundant Alcaligenes strains. Our findings expanded the understanding of the application of Dirammox bacteria as key functional microorganisms in a novel biological nitrogen and carbon removal process if they could be well stabilized. KEY POINTS: • Dirammox-dominated microbial community was enriched in activated sludge bioreactor. • The addition of hydroxylamine played a role in Dirammox enrichment. • Three Dirammox bacterial strains, including one novel species, were isolated.
Topics: Wastewater; Bioreactors; Nitrogen; Alcaligenes; Oxidation-Reduction; Sewage; Ammonia; Water Purification; Hydroxylamine; Phylogeny; RNA, Ribosomal, 16S; Bacteria; Microbiota
PubMed: 38904674
DOI: 10.1007/s00253-024-13214-2 -
Frontiers in Cellular and Infection... 2024is a prominent genus owing to its dual nature. Species of this genus have many applications in industry and agriculture as plant growth-promoting rhizobacteria and...
INTRODUCTION
is a prominent genus owing to its dual nature. Species of this genus have many applications in industry and agriculture as plant growth-promoting rhizobacteria and microbial biological control agents, whereas species such as are considered one of the leading gram-negative multi-drug-resistant bacterial pathogens because of their high contribution to the increase in crude mortality and significant clinical challenge. Pathogenic species and most clinical isolates belong to the complex (SMc). However, a strain highly homologous to was isolated from a patient with pulmonary tuberculosis (TB), which aroused our interest, as belongs to a relatively distant clade from SMc and there have been no human association reports.
METHODS
The pathogenicity, immunological and biochemical characteristics of 610A2 were systematically evaluated.
RESULTS
610A2 is a new species of genus , which is named as sp. nov. for its obvious brown water-soluble pigment. 610A2 is pathogenic and caused significant weight loss, pulmonary congestion, and blood transmission in mice because it has multiple virulence factors, haemolysis, and strong biofilm formation abilities. In addition, the cytokine response induced by this strain was similar to that observed in patients with TB, and the strain was resistant to half of the anti-TB drugs.
CONCLUSIONS
The pathogenicity of 610A2 may not be weaker than that of . Its isolation extended the opportunistic pathogenic species to all 3 major clades of the genus , indicating that the clinical importance of species of other than and potential risks to biological safety associated with the use of require more attention.
Topics: Stenotrophomonas; Animals; Phylogeny; Gram-Negative Bacterial Infections; Biofilms; Mice; Virulence Factors; RNA, Ribosomal, 16S; Humans; DNA, Bacterial; Sequence Analysis, DNA; Disease Models, Animal; Hemolysis; Bacterial Typing Techniques
PubMed: 38903940
DOI: 10.3389/fcimb.2024.1410385 -
PeerJ 2024Thunb., also known as Yuxingcao in Chinese, occupies a pivotal role in Asian traditional medicine and cuisine. The aerial parts and underground stems of exhibit...
Thunb., also known as Yuxingcao in Chinese, occupies a pivotal role in Asian traditional medicine and cuisine. The aerial parts and underground stems of exhibit remarkable chemical diversity, particularly in essential oil. Nevertheless, the mechanisms regulating essential oil biosynthesis in remain unclear. In this study, we present a quantitative overview of the proteomes across four tissues (flower, stem, leaf, and underground stem) of , achieved through the application of the isobaric tag for relative and absolute quantitation (iTRAQ). Our research findings indicate that certain crucial ribosomal proteins and their interactions may significantly impact the production of essential oils in . These results offer novel insights into the roles of ribosomal proteins and their associations in essential oil biosynthesis across various organisms of .
Topics: Houttuynia; Oils, Volatile; Ribosomal Proteins; Proteomics; Plant Proteins; Proteome
PubMed: 38903882
DOI: 10.7717/peerj.17519