The role of the tumor suppressor CYLD in Yersinia enterocolitica infection

Recent studies have identified the tumor suppressor CYLD as a key regulator of NF -κB, a transcription factor that promotes cell survival and oncogenesis, as well as host defence to infection. In th e pr esent study, we investigated the role of tumor suppressor CYLD in regulation of innate immune responses of mice to Y. enterocolitica infection and for comparison to Salmonella Typhimurium infection . Yersinia is an extracellular multiplying bacterium that ensures its extracellular growth by injecting virulence proteins (Yops) into host cells by the injectisome Ysc-T3SS , which interfere with several signaling pathways (such as MAPK and NF-κB cascades), resulting in the inhibition of phagocytosis, oxidative burst and cytokine production. In contrast, Salmonella Typhimurium is endowed with 2 T3SS which inject effector proteins to induce pathogen uptake and intracellular replication. Surprisingly, we found that Cyld-/- mice were more resistant to Y. enterocolitica than Cyld+/- mice in contrast to Salmonella Typimurium infection which appeared to be CYLD- independent. These results suggest that CYLD acts as a detrimental factor for host survival during early Y. enterocolitica infection. Furthermore, we showed that Yops-mediated inhibition of host defense mechanisms , such as phagocytosis, oxidative burst, NF-κB, cytokine production and p38 activation is attenuated in Cyld-/--phagocytic cells in respect of Cyld+/- cells. Taken together, this study provides for the first time, an empirical demonstration of a pathogen-specific contribution of a tumor suppressor gene and its encoded protein, respectively, CYLD, to infection susceptibility in a manner that seems to be independent of its tumor suppression mechanism. This is another example of the extraordinary complexity of the pathogen/host cell interactions

The impact of urban housing prices on labour mobility: evidence from cities in China

Urban development relies heavily on labour, while the change in urban housing prices, in turn, has a crucial impact on labour. Therefore, the regulatory policies of housing prices have become a critical content of urban management worldwide for a long time. Based on the theoretical analysis of urban housing prices and labour mobility, we use fixed-effect panel model with the panel data of 281 cities in China from 2002 to 2018. We study the impact of rising urban housing prices on labour and identify the housing price jump as an instrumental variable in solving the endogenous problem. The results are as follows. First, the increase in urban housing prices has a crowding-out effect on labour mobility. Second, there is a moderating effect on different levels of education, urban construction, and income under the impact of urban housing prices on labour mobility. Third, the heterogeneity of the impact is reflected in the housing price-to-income ratios and industrial structures. These conclusions are supposed to have significant enlightenment for controlling the urban housing prices during high-quality economic growth and guiding labour flow more rationally

Molecular genetic analysis of phosphomannomutase genes in Triticum monococcum

AbstractIn higher plants, phosphomannomutase (PMM) is essential for synthesizing the antioxidant ascorbic acid through the Smirnoff–Wheeler pathway. Previously, we characterized six PMM genes (TaPMM-A1, A2, B1, B2, D1 and D2) in common wheat (Triticum aestivum, AABBDD). Here, we report a molecular genetic analysis of PMM genes in Triticum monococcum (AmAm), a diploid wheat species whose Am genome is closely related to the A genome of common wheat. Two distinct PMM genes, TmPMM-1 and TmPMM-2, were found in T. monococcum. The coding region of TmPMM-1 was intact and highly conserved. In contrast, two main TmPMM-2 alleles were identified, with TmPMM-2a possessing an intact coding sequence and TmPMM-2b being a pseudogene. The transcript level of TmPMM-2a was much higher than that of TmPMM-2b, and a bacterially expressed TmPMM-2a recombinant protein displayed relatively high PMM activity. In general, the total transcript level of PMM was substantially higher in accessions carrying TmPMM-1 and TmPMM-2a than those harboring TmPMM-1 and TmPMM-2b. However, total PMM protein and activity levels did not differ drastically between the two genotypes. This work provides new information on PMM genes in T. monococcum and expands our understanding on Triticeae PMM genes, which may aid further functional and applied studies of PMM in crop plants

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional profiling of E7-expressing cells

The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G(1) cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7. At the transcriptome level, 236 genes were differentially expressed between E7 and vector control cells. A subset of the differentially expressed genes, most of them novel to E7-expressing cells, was further confirmed by real-time PCR. Of interest, the activities of multiple transcription factors were altered in E7-expressing cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were investigated. The upregulated genes were enriched in cell cycle and DNA replication, as well as in the DNA metabolic process, transcription, DNA damage, DNA repair, and nucleotide metabolism. Specifically, we focused our studies on the gene encoding WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein), one of the genes that was upregulated in E7-expressing cells. WDHD1 is a component of the replisome that regulates DNA replication. Recent studies suggest that WDHD1 may also function as a DNA replication initiation factor as well as a G(1) checkpoint regulator. We found that in E7-expressing cells, the steady-state level of WDHD1 protein was increased along with the half-life. Moreover, downregulation of WDHD1 reduced E7-induced G(1) checkpoint abrogation and rereplication, demonstrating a novel function for WDHD1. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. IMPORTANCE The high-risk HPV types induce cervical cancer and encode an E7 oncoprotein that plays a major role in HPV-induced carcinogenesis. However, the mechanism by which E7 induces carcinogenesis is not fully understood; specific anti-HPV agents are not available. In this study, we performed RNA-seq to characterize transcriptional profiling of keratinocytes expressing HPV-16 E7 and identified more than 200 genes that were differentially expressed between E7 and vector control cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were identified. Significantly, the WDHD1 gene, one of the genes that is upregulated in E7-expressing cells, was found to play an important role in E7-induced G(1) checkpoint abrogation and rereplication. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications

Association between dietary fiber intake and incidence of depression and anxiety in patients with essential hypertension

(1) Background: Our previous study found that the dietary fiber supplement in patients with hypertension increased SCFA-producers, Bifidobacterium and Spirillum in the gut microbiota, which may be associated with improvement of depression and anxiety through the gut–brain axis. However, only a few studies have explored the association between dietary fiber intake (DFI) and the incidence of depression and anxiety in hypertensive patients. (2) Methods: A cross-sectional survey was conducted in one comprehensive hospital and one community clinic aimed at understanding the status of DFI and the association between DFI and incidences of depression and anxiety in hypertensive patients. Levels of DFI were obtained through a two-24 h diet recall. According to the levels of DFI from low to high, the participants were divided into Q1, Q2, Q3 and Q4 groups. The Reported Outcomes Measurement Information System short form v1.0-Depression 8b and Anxiety 8a were used to assess patients’ levels of depression and anxiety. (3) Results: A total of 459 hypertensive patients were recruited and the daily DFI was 10.4 g. The incidences of hypertension combined with depression and anxiety were 19.6% and 18.5%, respectively. Regression analysis showed statistically significant associations between DFI and depression (B = −0.346, p = 0.001) and anxiety score (B = −0.565, p < 0.001). In logistic regression, after the covariates were adjusted, DFI was associated with the incidence of depression in Q3 (OR 2.641, 95% CI 1.050–6.640) and with that of anxiety in Q1 (OR 2.757, 95% CI 1.035–7.346), compared with Q4. (4) Conclusions: A higher consumption of DF was a protective factor for depression and anxiety in hypertensive patients

Physicochemical and Structural Properties of Pre-digested Puffed Rice Flours with Different Dextrose Equivalent Values

In the present study, pre-digested puffed rice flours with different dextrose equivalent (DE) values were prepared by using enzymatic pretreatment and extrusion, and their gelatinization characteristics, physicochemical and structural properties were analyzed. The results showed that compared with puffed rice flour, the water solubility index of pre-digested puffed rice flour increased by up to about 1.5 times with an increase in DE value, the water absorption index decreased by up to 76%, the slip angle decreased, the Carr index and Hausner ratio increased, and the reconstitutability and fluidity improved obviously. Moreover, the final viscosity and setback value of pre-digested puffed rice flour decreased with increasing DE value, decreasing by up to 37.79% and 94.87%, respectively. Moreover, after enzymatic pretreatment and extrusion, the soluble protein content of pre-digested puffed rice flour decreased, and the content of rapidly digestible starch increased significantly, while the secondary structure of protein and the crystalline structure of starch did not change significantly. The results provide a theoretical basis for the application of pre-digested puffed rice flour instead of maltodextrin in foods for special medical purpose

PTEN transcript variants caused by illegitimate splicing in “aged” blood samples and EBV-transformed cell lines

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Mutations occur in either heritable or sporadic fashion. Sequencing of cDNA from patients and normal individuals often reveals splicing variants (SVs) of PTEN, some of which are non-mutation related. To investigate whether these SVs were the result of illegitimate splicing (a general decrease of fidelity in splicing site selection in “aged” samples), we tested “aged” blood from individuals who had normal PTEN transcripts in their “fresh” mononuclear cells. Blood from 20 normal individuals was collected and split into two aliquots. Total RNA and DNA were extracted immediately (“fresh”) and 48 h later (“aged”), respectively. Using RT-PCR, subcloning and sequencing, we found seven types of SVs. No mutation was detected in the related intron–exon flanking region in genomic DNA in either “fresh” or “aged” samples. Some of the SVs were also consistently present in both the “fresh” and “aged” EBV-transformed lymphoblastoid cells from six normal individuals. Western blot data indicated that the PTEN protein level (in full length) was not altered in the “fresh” EBV-transformed lymphoblastoid cells with SVs. In conclusion, our data demonstrate that PTEN illegitimate splicing often occurs in “aged” blood and EBV-transformed lymphoblastoid cells. Therefore, it is critical to note the time point of RNA extraction when investigating for PTEN aberrant transcripts. We hope that our data will increase awareness about the sample status, because gene expression data may be potentially flawed from “aged” samples, particularly when dealing with clinical samples

Research on Corrosion Resistance and Formation Mechanism of Molybdate Composite Film

In order to reduce phosphorus pollution, the low phosphorus passivation process on Q235 steel was studied. The electrochemical method was used to test the corrosion resistance of sodium molybdate low phosphorus passivation. The polarization curve shows that the corrosion current of the sample passivated by low phosphorus is only 1/4 of that of the blank sample. Under scanning electron microscopy, the passivation film obtained by low phosphorus passivation treatment had the lowest phosphorus content and was more uniform and compact. The XPS (X-ray photoelectron spectroscopy) and OCP (open circuit potential) were used to study the film formation regularity and mechanism of low molybdenum sodium passivation. The results show that sodium molybdate low phosphorus passivation film has good corrosion resistance. The formation process of a passivation film can be divided into four stages alternating phosphating and passivation. The surface of the passivation film is mainly composed of phosphate, molybdate, molybdenum oxide, and their crystalline hydrates. The low phosphorus passivation process of sodium molybdate can reduce the concentration of phosphorus ions and reduce its pollution to the environment, which has broad application prospects

Research on Corrosion Resistance and Formation Mechanism of Molybdate Composite Film

In order to reduce phosphorus pollution, the low phosphorus passivation process on Q235 steel was studied. The electrochemical method was used to test the corrosion resistance of sodium molybdate low phosphorus passivation. The polarization curve shows that the corrosion current of the sample passivated by low phosphorus is only 1/4 of that of the blank sample. Under scanning electron microscopy, the passivation film obtained by low phosphorus passivation treatment had the lowest phosphorus content and was more uniform and compact. The XPS (X-ray photoelectron spectroscopy) and OCP (open circuit potential) were used to study the film formation regularity and mechanism of low molybdenum sodium passivation. The results show that sodium molybdate low phosphorus passivation film has good corrosion resistance. The formation process of a passivation film can be divided into four stages alternating phosphating and passivation. The surface of the passivation film is mainly composed of phosphate, molybdate, molybdenum oxide, and their crystalline hydrates. The low phosphorus passivation process of sodium molybdate can reduce the concentration of phosphorus ions and reduce its pollution to the environment, which has broad application prospects