共查询到20条相似文献，搜索用时 31 毫秒
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Jiseon Yang Jennifer Barrila Kenneth L. Roland Jacquelyn Kilbourne C. Mark Ott Rebecca J. Forsyth Cheryl A. Nickerson 《PLoS neglected tropical diseases》2015,9(6)
A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 105 CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580. 相似文献
3.
Senbagam Duraisamy Fazal Husain Senthilkumar Balakrishnan Aswathy Sathyan Prabhu Subramani Prahalathan Chidambaram Selvaraj Arokiyaraj Wahidah H. Al-Qahtani Jothiramalingam Rajabathar Anbarasu Kumarasamy 《Current issues in molecular biology》2022,44(2):731
Breast milk is the combination of bioactive compounds and microflora that promote newborn’s proper growth, gut flora, and immunity. Thus, it is always considered the perfect food for newborns. Amongst their bioactives, probiotic communities—especially lactic acid bacteria (LAB)—are characterized from breast milk over the first month of parturition. In this study, seven LAB were characterized phenotypically and genotypically as Levilactobacillus brevis BDUMBT08 (MT673657), L. gastricus BDUMBT09 (MT774596), L. paracasei BDUMBT10 (MT775430), L. brevis BDUMBT11 (MW785062), L. casei BDUMBT12 (MW785063), L. casei BDUMBT13 (MW785178), and Brevibacillus brevis M2403 (MK371781) from human breast milk. Their tolerance to lysozyme, acid, bile, gastric juice, pancreatic juice, and NaCl and potential for mucoadhesion, auto-aggregation, and co-aggregation with pathogens are of great prominence in forecasting their gut colonizing ability. They proved their safety aspects as they were negative for virulence determinants such as hemolysis and biofilm production. Antibiogram of LAB showed their sensitivity to more than 90% of the antibiotics tested. Amongst seven LAB, three isolates (L. brevis BDUMBT08 and BDUMBT11, and L. gatricus BDUMBT09) proved their bacteriocin producing propensity. Although the seven LAB isolates differed in their behavior, their substantial probiotic properties with safety could be taken as promising probiotics for further studies to prove their in vivo effects, such as health benefits, in humans. 相似文献
4.
Bryony N. Parsons Suzanne Humphrey Anne Marie Salisbury Julia Mikoleit Jay C. D. Hinton Melita A. Gordon Paul Wigley 《PLoS neglected tropical diseases》2013,7(10)
Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans. Oral infection of chickens with ST313 isolates D23580 and Q456 resulted in rapid infection of spleen and liver with all birds infected at these sites by 3 days post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98 and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused hepatosplenomegaly, and this was most pronounced in the ST313-infected animals. At 3 and 7 days post-infection, colonization of the gastrointestinal tract was lower in birds infected with the ST313 isolates compared with ST19. Histological examination and expression of CXCL chemokines in the ileum showed that both D23580 (ST313) and 4/74 (ST19) strains caused increased CXCL expression at 3 days post-infection, and this was significantly higher in the ileum of D23580 vs 4/74 infected birds. At 7 days post-infection, reduced chemokine expression occurred in the ileum of the D23580 but not 4/74-infected birds. Histological analysis showed that D23580 infection resulted in rapid inflammation and pathology including villous flattening and fusion at 3 days post-infection, and subsequent resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology at 3 days post-infection. The data presented demonstrate that ST313 is capable of causing invasive disease in a non-human host. The rapid invasive nature of infection in the chicken, coupled with lower gastrointestinal colonization, supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium that has evolved to become a systemic pathogen that can cause disease in several hosts. 相似文献
5.
damo Davi Digenes Siena Isabela Ichihara de Barros Camila Baldin Storti Carlos Alberto Oliveira de Biagi Júnior Larissa Anastacio da Costa Carvalho Silvya Stuchi Maria&#x;Engler Josane de Freitas Sousa Wilson Araújo Silva Jr 《Journal of cellular and molecular medicine》2022,26(3):671
Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance. 相似文献
6.
Lyubomir G. Nashev Anna Vuorinen Lukas Praxmarer Boonrat Chantong Diego Cereghetti Rahel Winiger Daniela Schuster Alex Odermatt 《PloS one》2012,7(10)
Background
Impaired corticosteroid action caused by genetic and environmental influence, including exposure to hazardous xenobiotics, contributes to the development and progression of metabolic diseases, cardiovascular complications and immune disorders. Novel strategies are thus needed for identifying xenobiotics that interfere with corticosteroid homeostasis. 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) and mineralocorticoid receptors (MR) are major regulators of corticosteroid action. 11β-HSD2 converts the active glucocorticoid cortisol to the inactive cortisone and protects MR from activation by glucocorticoids. 11β-HSD2 has also an essential role in the placenta to protect the fetus from high maternal cortisol concentrations.Methods and Principal Findings
We employed a previously constructed 3D-structural library of chemicals with proven and suspected endocrine disrupting effects for virtual screening using a chemical feature-based 11β-HSD pharmacophore. We tested several in silico predicted chemicals in a 11β-HSD2 bioassay. The identified antibiotic lasalocid and the silane-coupling agent AB110873 were found to concentration-dependently inhibit 11β-HSD2. Moreover, the silane AB110873 was shown to activate MR and stimulate mitochondrial ROS generation and the production of the proinflammatory cytokine interleukin-6 (IL-6). Finally, we constructed a MR pharmacophore, which successfully identified the silane AB110873.Conclusions
Screening of virtual chemical structure libraries can facilitate the identification of xenobiotics inhibiting 11β-HSD2 and/or activating MR. Lasalocid and AB110873 belong to new classes of 11β-HSD2 inhibitors. The silane AB110873 represents to the best of our knowledge the first industrial chemical shown to activate MR. Furthermore, the MR pharmacophore can now be used for future screening purposes. 相似文献7.
Yu Qi Qiao Mei Lan Huang An Tao Xu Di Zhao Zhi Hua Ran Jun Shen 《Journal of biomedical science》2013,20(1):87
Background
Long non-coding RNAs (lncRNAs) have different functions in cells. They work as signals, decoys, guides, and scaffolds. Altered lncRNA levels can affect the expression of gene products. There are seldom studies on the role of lncRNAs in inflammatory bowel disease (IBD).Results
Quantitative RT-PCR showed that DQ786243 was significantly overexpressed in clinical active CD patients compared with clinical inactive CD patients (P = 0.0118) or healthy controls (P = 0.002). CREB was also more highly expressed in active CD than in inactive CD (P = 0.0034) or controls (P = 0.0241). Foxp3 was interestingly lower in inactive CD than in active CD (P = 0.0317) or controls (P = 0.0103), but there were no apparent differences between active CD and controls. CRP was well correlated with DQ786243 (r = 0.489, P = 0.034), CREB (r = 0.500, P = 0.029) and Foxp3 (r = 0.546, P = 0.016). At 48 hours after DQ786243 transfection, qRT-PCR showed both CREB (P = 0.017) and Foxp3 (P = 0.046) had an increased mRNA expression in Jurkat cells. Western blot showed the same pattern. After DQ786243 transfection, CREB phosphorylation ratio (p-CREB/t-CREB) was increased (P = 0.0043).Conclusion
DQ786243 can be related with severity of CD. It can affect the expression of CREB and Foxp3 through which regulates the function of Treg. CREB itself seems not the mediator of DQ786243 to up-regulate Foxp3. The phosphorylation of CREB might play a more important role in the process. 相似文献8.
Wanli Du Jing Wang Liangming Wang Jun Zhang Xinhong Chen Jixin Zhao Qunhui Yang Jun Wu 《PloS one》2013,8(8)
The aim of this study was to characterize a Triticum aestivum-Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs) disomic addition line 2-1-6-3. Individual line 2-1-6-3 plants were analyzed using cytological, genomic in situ hybridization (GISH), EST-SSR, and EST-STS techniques. The alien addition line 2-1-6-3 was shown to have two P. huashanica chromosomes, with a meiotic configuration of 2n = 44 = 22 II. We tested 55 EST-SSR and 336 EST-STS primer pairs that mapped onto seven different wheat chromosomes using DNA from parents and the P. huashanica addition line. One EST-SSR and nine EST-STS primer pairs indicated that the additional chromosome of P. huashanica belonged to homoeologous group 7, the diagnostic fragments of five EST-STS markers (BE404955, BE591127, BE637663, BF482781 and CD452422) were cloned, sequenced and compared. The results showed that the amplified polymorphic bands of P. huashanica and disomic addition line 2-1-6-3 shared 100% sequence identity, which was designated as the 7Ns disomic addition line. Disomic addition line 2-1-6-3 was evaluated to test the leaf rust resistance of adult stages in the field. We found that one pair of the 7Ns genome chromosomes carried new leaf rust resistance gene(s). Moreover, wheat line 2-1-6-3 had a superior numbers of florets and grains per spike, which were associated with the introgression of the paired P. huashanica chromosomes. These high levels of disease resistance and stable, excellent agronomic traits suggest that this line could be utilized as a novel donor in wheat breeding programs. 相似文献
9.
Background
There is large variability among lung squamous cell carcinoma patients in response to treatment with cisplatin based chemotherapy. LncRNA is potentially a new type of predictive marker that can identify subgroups of patients who benefit from chemotherapy and it will have great value for treatment guidance.Methods
Differentially expressed lncRNAs and mRNA were identified using microarray profiling of tumors with partial response (PR) vs. with progressive disease (PD) from advanced lung squamous cell carcinoma patients treated with cisplatin based chemotherapy and validated by quantitative real-time PCR (qPCR). Furthermore, the expression of AC006050.3-003 was assessed in another 60 tumor samples.Results
Compared with the PD samples, 953 lncRNAs were consistently upregulated and 749 lncRNAs were downregulated consistently among the differentially expressed lncRNAs in PR samples (Fold Change≥2.0-fold, p <0.05). Pathway analyses showed that some classical pathways, including “Nucleotide excision repair,” that participated in cisplatin chemo response were differentially expressed between PR and PD samples. Coding-non-coding gene co-expression network identified many lncRNAs, such as lncRNA AC006050.3-003, that potentially played a key role in chemo response. The expression of lncRNA AC006050.3-003 was significantly lower in PR samples compared to the PD samples in another 60 lung squamous cell carcinoma patients. Receiver operating characteristic curve analysis revealed that lncRNA AC006050.3-003 was a valuable biomarker for differentiating PR patients from PD patients with an area under the curve of 0.887 (95% confidence interval 0.779, 0.954).Conclusions
LncRNAs seem to be involved in cisplatin-based chemo response and may serve as biomarkers for treatment response and candidates for therapy targets in lung squamous cell carcinoma. 相似文献10.
The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.
- Phylum Crenarchaeota
- Thermoproteus tenax, strain Kra1, DSM 2078T sequence accession FN869859 [1]
- Phylum Euryarchaeota
- Haloarcula hispanica CGMCC 1.2049, sequence accession CP002921 (chromosome I), CP002922 (chromosome II), and CP002923 (plasmid pHH400) [2]
- Methanococcus maripaludis, strain X1 (unculturable) sequence accession CP002913 [3]
- Phylum Proteobacteria
- Acinetobacter baumannii strain 1656-2, sequence accession CP001921 [4]
- Arcobacter butzleri strain ED-1, sequence accession AP012047, AP012048, and AP012049 [5]
- Brucella suis strain 1330, sequence accession CP002997 and CP002998 [6]
- Campylobacter fetus subsp. venerealis NCTC 10354, sequence accession AFGH01000000 [7]
- “Chromobacterium sp.” strain C-61, sequence accession CAEE01000001 to CAEE01001118 [8]
- Cronobacter sakazakii strain E899, sequence accession AFMO00000000 [9]
- “Desulfovibrio sp.” strain A2, sequence accession AGFG01000000 [10]
- “Erythrobacter sp.” strain NAP1, sequence accession NZ_AAMW00000000 [11]
- Escherichia coli strain XH140A, sequence accession AFVX01000000 [12]
- Escherichia coli strain XH001, sequence accession AFYG01000000 [13]
- Haemophilus haemolyticus strain M19107, sequence accession AFQN00000000 [14]
- Haemophilus haemolyticus strain M19501, sequence accession AFQO00000000 [14]
- Haemophilus haemolyticus strain M21127, sequence accession AFQP00000000 [14]
- Haemophilus haemolyticus strain M21621, sequence accession AFQQ00000000 [14]
- Haemophilus haemolyticus strain M21639, sequence accession AFQR00000000 [14]
- Idiomarina sp.” strain A28L, sequence accession AFPO01000001 to AFPO01000028 [15]
- Ketogulonicigenium vulgare” strain WSH-001, sequence accession CP002018 (chromosome), CP002019 (plasmid pKVU_100), and CP002020 (plasmid pKVU_200) [16]
- Methylobacter tundripaludum strain SV96, sequence accession AEGW00000000 [17]
- Pseudogulbenkiania sp.” strain NH8B, sequence accession AP012224 [18]
- Pseudomonas aeruginosa NCGM1179, sequence accession DF126593 through DF126613 [19]
- Pseudomonas putida strain B001, sequence accession CAED01000001 to CAEE01000262 [20]
- Pseudomonas putida strain B6-2, sequence accession AGCS01000000 [21]
- Pseudomonas stutzeri CGMCC 1.1803, sequence accession CP002881 [22]
- Ralstonia solanacearum phylotype IB, strain Y45, sequence accession AFWL01000000 [23]
- Rheinheimera sp.” strain A13L, sequence accession AFHI01000001 through AFHI01000072 [24]
- Sphingobium yanoikuyae strain XLDN2-5, sequence accession AFXE01000000 [25]
- Vibrio cholerae strain Amazonia, sequence accession AFSV01000000 [26]
- Phylum Firmicutes
- Bacillus coagulans strain XZL4, sequence accession AFWM01000000 [27]
- Bacillus megaterium strain WSH-002, sequence accession CP003017 (chromosome), plasmids CP003018 (plasmid pBME_100), CP003019 (plasmid pBME_200), and CP003020 (plasmid pBME_300) [28]
- Bacillus pumilus strain S-1, sequence accession AGBY00000000 [29]
- “Desulfosporosinus sp.” strain OT, sequence accession AGAF01000000 [30]
- Lentibacillus jeotgali strain Grbi, sequence accession AGAV01000000 [31]
- Leuconostoc carnosum KCTC 3525, sequence accession BACM01000000 [32]
- Listeria ivanovii subsp. ivanovii strain PAM 55, sequence accession FR687253 [33]
- Paenibacillus riograndensis strain SBR5, sequence accession AGBD01000000 [34]
- Sporolactobacillus inulinus strain CASD, sequence accession AFVQ00000000 [35]
- Streptococcus pseudopneumoniae strain IS7493, sequence accession CP002925 and CP002926 [36]
- Streptococcus salivarius strain 57.I, sequence accession CP002888 and CP002889 [37]
- Streptococcus salivarius strain M18, sequence accession AGBV01000000 [38]
- Streptococcus suis SS12, sequence accession CP002640 [39]
- Streptococcus suis D9, sequence accession CP002641 [39]
- Streptococcus suis D12, sequence accession CP002644 [39]
- Streptococcus suis ST1, sequence accession CP002651 [39]
- Weissella thailandensis strain fsh4-2, sequence accession HE575133 through HE575182 [40]
- Phylum Tenericutes
- Mycoplasma anatis strain 1340, sequence accession AFVJ00000000 [41]
- Mycoplasma capricolum subsp. capripneumoniae strain M1601, sequence accession AENG01000000 [42]
- Mycoplasma putrefaciens Type strain KS1, sequence accession CP003021 [43]
- Corynebacterium pseudotuberculosis strain PAT10, sequence accession CP002924 [44]
- Phylum Actinobacteria
- Bifidobacterium animalis subsp. lactis strain BLC1, sequence accession CP003039 [45]
- Bifidobacterium breve strain DPC 6330, sequence accession AFXX01000000 [46]
- Brachybacterium squillarum strain M-6-3, sequence accession AGBX01000000 [47]
- “Citricoccus sp.” strain CH26A, sequence accession AFXQ01000000 [48]
- Corynebacterium glutamicum strain S9114, sequence accession AFYA01000000 [49]
- Dietzia alimentaria strain 72, sequence accession AGFF01000000 [50]
- Mycobacterium colombiense CECT 3035, sequence accession AFVW00000000 [51]
- Mycobacterium tuberculosis NCGM2209, sequence accession DF126614 and DF126615 [52]
- Rhodococcus erythropolis strain XP, sequence accession AGCF01000000 [53]
- Serinicoccus profundi MCCC 1A05965T, sequence accession AFYF00000000 [54]
- Phylum Spirochaetes
- Leptospira interrogans, sequence accession CP001221 (CI), CP001222 (CII) [55]
- Phylum Bacteroidetes
- Bacteroides faecis Type strain MAJ27T, sequence accession AGDG01000000 [56]
- Bizionia argentinensis, Type strain JUB59T sequence accession AFXZ01000000 [57]
- Flavobacterium branchiophilum strain FL-15, sequence accession FQ859183 [58]
- “Flavobacteriaceae” strain S85, sequence accession AFPK00000000 [59]
- Phylum Thermotogae
- “Thermotoga sp.” strain RQ2, sequence accession CP000969 [60]
Non-Bacterial genomes
- Aspergillus kawachii IFO 4308, sequence accession DF126447 through DF126592, BACL01000001 through BACL01001641, AP012272 [61]
- Cajanus cajan pigeonpea, sequence accession PRJNA72815 [62]
- Coxsackievirus A22, sequence accession JN542510 [63]
- Gordonia phage GRU1, sequence accession JF923797 [64]
- Gordonia phage GTE5, sequence accession JF923796 [64]
- Heterocephalus glaber naked mole rat, sequence accession AFSB00000000, AFSB01000000 [65]
- Human Adenovirus Prototype 17, sequence accession HQ910407 [66]
- Macaca mulatta lasiota rhesus macaque, sequence accession AEHL00000000 [67]
- Macaca mulatta mulatta rhesus macaque, sequence accession AEHK00000000 [67]
- Porcine epidemic diarrhea virus, sequence accession JN547228 [68]
11.
In this short report, the genome-wide homologous recombination events were re-evaluated for classical swine fever virus (CSFV) strain AF407339. We challenged a previous study which suggested only one recombination event in AF407339 based on 25 CSFV genomes. Through our re-analysis on the 25 genomes in the previous study and the 41 genomes used in the present study, we argued that there should be possibly at least two clear recombination events happening in AF407339 through genome-wide scanning. The reasons for identifying only one recombination event in the previous study might be due to the limited number of available CSFV genome sequences at that time and the limited usage of detection methods. In contrast, as identified by most detection methods using all available CSFV genome sequences, two major recombination events were found at the starting and ending zones of the genome AF407339, respectively. The first one has two parents AF333000 (minor) and AY554397 (major) with beginning and ending breakpoints located at 19 and 607 nt of the genome respectively. The second one has two parents AF531433 (minor) and GQ902941 (major) with beginning and ending breakpoints at 8397 and 11,078 nt of the genome respectively. Phylogenetic incongruence analysis using neighbor-joining algorithm with 1000 bootstrapping replicates further supported the existence of these two recombination events. In addition, we also identified additional 18 recombination events on the available CSFV strains. Some of them may be trivial and can be ignored. In conclusion, CSFV might have relatively high frequency of homologous recombination events. Genome-wide scanning of identifying recombination events should utilize multiple detection methods so as to reduce the risk of misidentification. 相似文献
12.
Group I mGluRs (metabotropic glutamate receptors), including mGluR1 and mGluR5, are GPCRs (G-protein coupled receptors) and play important roles in physiology and pathology. Studies on their role in cerebral ischaemia have provided controversial results. In this study, we used a PT (photothrombosis)-induced ischaemia model to investigate whether antagonists to the group I mGluRs may offer acute and long-term protective effects in adult mice. Our results demonstrated that administration with mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine] or mGluR1 antagonist LY367385 by intraperitoneal injection at 3 h after PT decreased brain infarct volume evaluated one day after ischaemia. Additive effects on infarct volume were observed upon co-injection with MPEP and LY367385. These antagonists also significantly alleviated neurodegeneration and apoptosis in the penumbra. In addition, when evaluated 2 weeks after PT, they reduced infarct volume and tissue loss, attenuated glial scar formation, and inhibited cell proliferation in the penumbra. Importantly, co-injection with MPEP and LY367385 reduced the expression levels of calpain, a Ca2+-activated protease known to mediate ischaemia-induced neuronal death. Injection of calpeptin, a calpain inhibitor, could inhibit neuronal death and brain damage after PT but injection of calpeptin together with MPEP and LY367385 did not further improve the protective effects mediated by MPEP and LY367385. These results suggest that inhibition of group I mGluRs is sufficient to protect ischaemic damage through the calpain pathway. Taken together, our results demonstrate that inhibition of group I mGluRs can mitigate PT-induced brain damage through attenuating the effects of calpain, and improve long-term histological outcomes. 相似文献
13.
DNA glycosylases are important repair enzymes that eliminate a diverse array of aberrant nucleobases from the genomes of all organisms. Individual bacterial species often contain multiple paralogs of a particular glycosylase, yet the molecular and functional distinctions between these paralogs are not well understood. The recently discovered HEAT-like repeat (HLR) DNA glycosylases are distributed across all domains of life and are distinct in their specificity for cationic alkylpurines and mechanism of damage recognition. Here, we describe a number of phylogenetically diverse bacterial species with two orthologs of the HLR DNA glycosylase AlkD. One ortholog, which we designate AlkD2, is substantially less conserved. The crystal structure of Streptococcus mutans AlkD2 is remarkably similar to AlkD but lacks the only helix present in AlkD that penetrates the DNA minor groove. We show that AlkD2 possesses only weak DNA binding affinity and lacks alkylpurine excision activity. Mutational analysis of residues along this DNA binding helix in AlkD substantially reduced binding affinity for damaged DNA, for the first time revealing the importance of this structural motif for damage recognition by HLR glycosylases. 相似文献
14.
Shuanglin Peng Yujin Gao Sirong Shi Dan Zhao Huayue Cao Ting Fu Xiaoxiao Cai Jingang Xiao 《Cell proliferation》2022,55(1)
ObjectivesBone tissue engineering based on adipose‐derived stem cells (ASCs) is expected to become a new treatment for diabetic osteoporosis (DOP) patients with bone defects. However, compared with control ASCs (CON‐ASCs), osteogenic potential of DOP‐ASCs is decreased, which increased the difficulty of bone reconstruction in DOP patients. Moreover, the cause of the poor osteogenesis of ASCs in a hyperglycemic microenvironment has not been elucidated. Therefore, this study explored the molecular mechanism of the decline in the osteogenic potential of DOP‐ASCs from the perspective of epigenetics to provide a possible therapeutic target for bone repair in DOP patients with bone defects.Materials and methodsAn animal model of DOP was established in mice. CON‐ASCs and DOP‐ASCs were isolated from CON and DOP mice, respectively. AK137033 small interfering RNA (SiRNA) and an AK137033 overexpression plasmid were used to regulate the expression of AK137033 in CON‐ASCs and DOP‐ASCs in vitro. Lentiviruses that carried shRNA‐AK137033 or AK137033 cDNA were used to knockdown or overexpress AK137033, respectively, in CON‐ASCs and DOP‐ASCs in vivo. Hematoxylin and eosin (H&E), Masson''s, alizarin red, and alkaline phosphatase (ALP) staining, micro‐computed tomography (Micro‐CT), flow cytometry, qPCR, western blotting, immunofluorescence, and bisulfite‐specific PCR (BSP) were used to analyze the functional changes of ASCs.ResultsThe DOP mouse model was established successfully. Compared with CON‐ASCs, AK137033 expression, the DNA methylation level of the sFrp2 promoter region, Wnt signaling pathway markers, and the osteogenic differentiation potential were decreased in DOP‐ASCs. In vitro experiments showed that AK137033 silencing inhibited the Wnt signaling pathway and osteogenic ability of CON‐ASCs by reducing the DNA methylation level in the sFrp2 promoter region. Additionally, overexpression of AK137033 in DOP‐ASCs rescued these changes caused by DOP. Moreover, the same results were obtained in vivo.ConclusionsLncRNA‐AK137033 inhibits the osteogenic potential of DOP‐ASCs by regulating the Wnt signaling pathway via modulating the DNA methylation level in the sFrp2 promoter region. This study provides an important reference to find new targets for the treatment of bone defects in DOP patients. 相似文献
15.
Purpose
To investigate the effects of hypoxic conditioned media from rat cerebral cortical cells on the proliferation and differentiation of neural stem cells (NSCs) in vitro, and to study the roles of PI3-K/Akt and JNK signal transduction pathways in these processes.Methods
Cerebral cortical cells from neonatal Sprague–Dawley rat were cultured under hypoxic and normoxic conditions; the supernatant was collected and named ‘hypoxic conditioned medium’ (HCM) and ‘normoxic conditioned medium’ (NCM), respectively. We detected the protein levels (by ELISA) of VEGF and BDNF in the conditioned media and mRNA levels (by RT-PCR) in cerebral cortical cells. The proliferation (number and size of neurospheres) and differentiation (proportion of neurons and astrocytes over total cells) of NSCs was assessed. LY294002 and SP600125, inhibitors of PI3-K/Akt and JNK, respectively, were applied, and the phosphorylation levels of PI3-K, Akt and JNK were measured by western blot.Results
The protein levels and mRNA expressions of VEGF and BDNF in 4% HCM and 1% HCM were both higher than that of those in NCM. The efficiency and speed of NSCs proliferation was enhanced in 4% HCM compared with 1% HCM. The highest percentage of neurons and lowest percentage of astrocytes was found in 4% HCM. However, the enhancement of NSCs proliferation and differentiation into neurons accelerated by 4% HCM was inhibited by LY294002 and SP600125, with LY294002 having a stronger inhibitory effect. The increased phosphorylation levels of PI3-K, Akt and JNK in 4% HCM were blocked by LY294002 and SP600125.Conclusions
4%HCM could promote NSCs proliferation and differentiation into high percentage of neurons, these processes may be mainly through PI3-K/Akt pathways. 相似文献16.
The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.
Phylum Euryarchaeota
- Halococcus hamelinensis, sequence accession PRJNA80845 [1]
- “Methanocella conradii” HZ254, sequence accession CP003243 [2]
- Thermococcus litoralis NS-C, sequence accession AHVB00000000 [3]
Phylum Crenarchaeota
- Candidatus Nitrosopumilus salaria” BD31, sequence accession AEXL00000000 [4]
- Candidatus Nitrosoarchaeum limnia, sequence accession AHJG00000000 [5]
Phylum Deinococcus-Thermus
Phylum Proteobacteria
- Aggregatibacter actinomycetemcomitans strain ANH9381, sequence accession CP003099 [7]
- Alishewanella jeotgali, sequence accession AHTH00000000 [8]
- Enterobacter aerogenes KCTC 2190, sequence accession CP002824 [9]
- Escherichia coli O104:H4, sequence accession AFOB02000092 [10]
- Helicobacter pylori strains 17874, sequence accession PRJNA76569 [11]
- Helicobacter pylori strains P79, sequence accession PRJNA76567 [11]
- Janthinobacterium sp. Strain PAMC 25724, sequence accession AHHB00000000 [12]
- Klebsiella oxytoca KCTC 1686, sequence accession CP003218 [13]
- Klebsiella pneumoniae subsp. pneumoniae HS11286, sequence accession CP003200 (chromosome), CP003223 (plasmid pKPHS1), CP003224 (plasmid pKPHS2), CP003225 (plasmid pKPHS3), CP003226 (plasmid pKPHS4), CP003227 (plasmid pKPHS5), CP003228 (plasmid pKPHS6) [14]
- Oceanimonas sp. GK1, sequence accession CP003171 [15]
- “Pseudogulbenkiania ferrooxidans” Strain 2002, sequence accession NZ_ACIS01000000 [16]
- Pseudomonas extremaustralis 14-3b, sequence accession AHIP00000000 [17]
- Pseudomonas sp. Strain PAMC 25886, sequence accession AHHC00000000 [18]
- Psychrobacter, sequence accession AHVZ00000000 [19]
- Rahnella sp. Strain Y9602, sequence accession CP002505 [20]
- Rhizobium sp. Strain PDO1-076, sequence accession AHZC00000000 [21]
- Rhodospirillum photometricum DSM122, sequence accession HE663493 [22]
- “Rickettsia sibirica sibirica”, sequence accession AHIZ00000000 [23]
- Rickettsia sibirica subsp. mongolitimonae strain HA-91, sequence accession AHZB00000000 [24]
- Salmonella enterica subsp. enterica Serotype Enteritidis Strain LA5, sequence accession [25]
- Salmonella enterica subsp. enterica Serotype Senftenberg Strain SS209, sequence accession CAGQ00000000 [26]
- Salmonella enterica subsp. enterica Serovar Typhi P-stx-12, sequence accession CP003278 (chromosome) and CP003279 (plasmid) [27]
- Sphingomonas echinoides ATCC 14820, sequence accession AHIR00000000 [28]
- Strain HIMB55, sequence accession AGIF00000000 [29]
- Vibrio harveyi CAIM 1792, sequence accession AHHQ00000000 [30]
- Wolbachia Strain wAlbB, sequence accession CAGB01000001 to CAGB01000165 [31]
- Xanthomonas axonopodis pv. punicae Strain LMG 859, sequence accession CAGJ01000001 to CAGJ01000217 [32]
Phylum Tenericutes
Phylum Firmicutes
- Bacillus subtilis, sequence accession BGSCID 3A27 through BGSCID 28A4 [34]
- Clostridium difficile Strain CD37, sequence accession AHJJ00000000 [35]
- Clostridium perfringens, sequence accession AFES00000000 [36]
- Lactobacillus fructivorans KCTC 3543, sequence accession AEQY00000000 [37]
- Lactococcus lactis IO-1, sequence accession AP012281 [38]
- Lactobacillus plantarum strain NC8, sequence accession AGRI00000000 [39]
- Paenibacillus dendritiformis C454, sequence accession AHKH00000000 [40]
- Paenibacillus sp. Strain Aloe-11, sequence accession AGFI00000000 [41]
- “Peptoniphilus rhinitidis” 1-13T, sequence accession BAEW01000001 to BAEW01000056 [42]
- Streptococcus macedonicus ACA-DC 198, sequence accession HE613569 and HE613570 [43]
- Staphylococcus aureus VC40, sequence accession CP003033 [44]
- Streptococcus infantarius subsp. infantarius Strain CJ18, sequence accession CP003295 (chromosome), CP003296 (plasmid) [45]
- Streptococcus macedonicus ACA-DC 198, sequence accession HE613569 (chromosome), HE613570 (plasmid pSMA198) [46]
Phylum Actinobacteria
- Actinoplanes sp. SE50/110, sequence accession CP003170 [47]
- Amycolatopsis sp. Strain ATCC 39116, sequence accession [48]
- Nocardia cyriacigeorgica GUH-2, sequence accession FO082843 [49]
- Salinibacterium sp., sequence accession AHWA00000000 [50]
- Streptomyces acidiscabies 84-104, sequence accession AHBF00000000 [51]
Non-Bacterial genomes
- Bluetongue Virus Serotype 2, sequence accession AJ783905 (Seg-6) and JQ681257 (Seg-1), JQ681257 (Seg-1), JQ681258 (Seg-2), JQ681259 (Seg-3), JQ681260 (Seg-4), JQ681261 (Seg-5), JQ681262 (Seg-7), JQ6812563 (Seg-8), JQ6812564 (Seg-9), to JQ681265 (Seg-10) [52]
- Virus Serotype 1, sequence accession AJ585111 (Seg-2), AJ586659 (Seg-6), JQ282770 (Seg-1), JQ282771 (Seg-3), JQ282772 (Seg-4), JQ282773 (Seg-5), JQ282774 (Seg-7), JQ282775 (Seg-8), JQ282776 (Seg-9), and JQ282777 (Seg-10) [52]
- Chloroplast genome of Erycina pusilla, sequence accession JF_746994 [53]
- Danio rerio, sequence accession JQ434101 [54]
- Enterococcal Bacteriophage SAP6, sequence accession JF731128 [55]
- Eubenangee virus, sequence accession JQ070376 through JQ070385 [56]
- Fujian/411-like viruses, sequence accession CY087969 to CY088568 [57]
- Hantavirus Variant of Rio Mamoré Virus, Maripa Virus, sequence accession JQ611712 (segment S), JQ611713 (segment M), and JQ611714 (segment L) [58]
- Pata virus, sequence accession JQ070386 through JQ070395 [59]
- Porcine Circovirus 2, sequence accession JQ413808 [60]
- Porcine Reproductive and Respiratory Syndrome Virus, sequence accession JQ326271 [61]
- Streptococcus mutans Phage M102AD, sequence accession DQ386162 [62]
- Tilligery virus, sequence accession JQ070366 through JQ070375 [63]
17.
DNA sequencing has been revolutionized by the development of high-throughput sequencing technologies. Plummeting costs and the massive throughput capacities of second and third generation sequencing platforms have transformed many fields of biological research. Concurrently, new data processing pipelines made rapid de novo genome assemblies possible. However, high quality data are critically important for all investigations in the genomic era. We used chloroplast genomes of one Oryza species (O. australiensis) to compare differences in sequence quality: one genome (GU592209) was obtained through Illumina sequencing and reference-guided assembly and the other genome (KJ830774) was obtained via target enrichment libraries and shotgun sequencing. Based on the whole genome alignment, GU592209 was more similar to the reference genome (O. sativa: AY522330) with 99.2% sequence identity (SI value) compared with the 98.8% SI values in the KJ830774 genome; whereas the opposite result was obtained when the SI values in coding and noncoding regions of GU592209 and KJ830774 were compared. Additionally, the junctions of two single copies and repeat copies in the chloroplast genome exhibited differences. Phylogenetic analyses were conducted using these sequences, and the different data sets yielded dissimilar topologies: phylogenetic replacements of the two individuals were remarkably different based on whole genome sequencing or SNP data and insertions and deletions (indels) data. Thus, we concluded that the genomic composition of GU592209 was heterogeneous in coding and non-coding regions. These findings should impel biologists to carefully consider the quality of sequencing and assembly when working with next-generation data. 相似文献
18.
19.
The small chaperone protein Hsp27 confers resistance to apoptosis, and therefore is an attractive anticancer drug target. We report here a novel mechanism underlying the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitizing activity of the small molecule LY303511, an inactive analog of the phosphoinositide 3-kinase inhibitor inhibitor LY294002, in HeLa cells that are refractory to TRAIL-induced apoptosis. On the basis of the fact that LY303511 is derived from LY294002, itself derived from quercetin, and earlier findings indicating that quercetin and LY294002 affected Hsp27 expression, we investigated whether LY303511 sensitized cancer cells to TRAIL via a conserved inhibitory effect on Hsp27. We provide evidence that upon treatment with LY303511, Hsp27 is progressively sequestered in the nucleus, thus reducing its protective effect in the cytosol during the apoptotic process. LY303511-induced nuclear translocation of Hsp27 is linked to its sustained phosphorylation via activation of p38 kinase and MAPKAP kinase 2 and the inhibition of PP2A. Furthermore, Hsp27 phosphorylation leads to the subsequent dissociation of its large oligomers and a decrease in its chaperone activity, thereby further compromising the death inhibitory activity of Hsp27. Furthermore, genetic manipulation of Hsp27 expression significantly affected the TRAIL sensitizing activity of LY303511, which corroborated the Hsp27 targeting activity of LY303511. Taken together, these data indicate a novel mechanism of small molecule sensitization to TRAIL through targeting of Hsp27 functions, rather than its overall expression, leading to decreased cellular protection, which could have therapeutic implications for overcoming chemotherapy resistance in tumor cells. 相似文献
20.
Endophytic fungi isolated from Catharanthus roseus were screened for the production of vincristine and vinblastine. Twenty-two endophytic fungi isolated from various tissues of C. roseus were characterized taxonomically by sequence analysis of the internal transcribed spacer (ITS) region of rDNA and grouped into 10 genera: Alternaria, Aspergillus, Chaetomium, Colletotrichum, Dothideomycetes, Eutypella, Eutypa, Flavodon, Fusarium and Talaromyces. The antiproliferative activity of these fungi was assayed in HeLa cells using the MTT assay. The fungal isolates Eutypella sp—CrP14, obtained from stem tissues, and Talaromyces radicus—CrP20, obtained from leaf tissues, showed the strongest antiproliferative activity, with IC50 values of 13.5 μg/ml and 20 μg/ml, respectively. All 22 endophytic fungi were screened for the presence of the gene encoding tryptophan decarboxylase (TDC), the key enzyme in the terpenoid indole alkaloid biosynthetic pathway, though this gene could only be amplified from T. radicus—CrP20 (NCBI GenBank accession number KC920846). The production of vincristine and vinblastine by T. radicus—CrP20 was confirmed and optimized in nine different liquid media. Good yields of vincristine (670 μg/l) in modified M2 medium and of vinblastine (70 μg/l) in potato dextrose broth medium were obtained. The cytotoxic activity of partially purified fungal vincristine was evaluated in different human cancer cell lines, with HeLa cells showing maximum susceptibility. The apoptosis-inducing activity of vincristine derived from this fungus was established through cell cycle analysis, loss of mitochondrial membrane potential and DNA fragmentation patterns. 相似文献