Molecular epidemiology of hepatitis E virus infections in Shanghai, China

<p>Abstract</p> <p>Background</p> <p>Hepatitis E virus (HEV) causes acute or fulminant hepatitis in humans and is an important public health concern in many developing countries. China has a high incidence of HEV epidemics, with at least three genotypes (1, 3 and 4) and nine subtypes (1b, 1c, 3b, 4a, 4b, 4d, 4g, 4h and 4i) so far identified. Since genotype 3 and the newly identified subtype 4i have been exclusively limited geographically to Shanghai and its neighboring provinces, the epidemiology of HEV infections within the municipality, a major industrial and commercial center, deserves closer attention.</p> <p>Findings</p> <p>A total of 65 sequences, 60 located within the HEV SH-SW-zs1 genome [GenBank:<ext-link ext-link-id="EF570133" ext-link-type="gen">EF570133</ext-link>], together with five full-length swine and human HEV genomic sequences, all emanating from Shanghai, were retrieved from GenBank. Consistent with the primary role of genotype 4 in China overall, analysis of the sequences revealed this to have been the dominant genotype (58/65) in Shanghai. Six HEV subtypes (3b, 4a, 4b, 4d, 4h and 4i) were also represented. However, although subtype 4a is the dominant subtype throughout China, subtype 4i (29/65) was the most prevalent subtype among the Shanghai sequences, followed by subtypes 4d (10/65) and 4h (9/65). Subtypes 4h, 4i and 4d were found in both swine and humans, whereas 4b was found only in swine and subtype 4a only in humans.</p> <p>Conclusions</p> <p>Six different swine and human HEV subtypes have so far been documented in Shanghai. More molecular epidemiological investigations of HEV in swine, and particularly among the human population, should be undertaken.</p

Role of phosphatase of regenerating liver 1 (PRL1) in spermatogenesis

The PRL phosphatases are oncogenic when overexpressed but their in vivo biological function is less well understood. Previous gene deletion study revealed a role for PRL2 in spermatogenesis. We report here the first knockout mice lacking PRL1, the most related homolog of PRL2. We found that loss of PRL1 does not affect spermatogenesis and reproductive ability of male mice, likely due to functional compensation by the relatively higher expression of PRL2 in the testes. However, PRL1-/-/PRL2+/- male mice show testicular atrophy phenotype similar to PRL2-/- mice. More strikingly, deletion of one PRL1 allele in PRL2-/- male mice causes complete infertility. Mechanistically, the total level of PRL1 and PRL2 is negatively correlated with the PTEN protein level in the testis and PRL1+/-/PRL2-/- mice have the highest level of PTEN, leading to attenuated Akt activation and increased germ cell apoptosis, effectively halting spermatozoa production. These results provide the first evidence that in addition to PRL2, PRL1 is also required for spermatogenesis by downregulating PTEN and promoting Akt signaling. The ability of the PRLs to suppress PTEN expression underscores the biochemical basis for their oncogenic potential

PRL2/PTP4A2 phosphatase is important for hematopoietic stem cell self-renewal

Hematopoietic stem cell (HSC) self-renewal is tightly controlled by cytokines and other signals in the microenvironment. While stem cell factor (SCF) is an early acting cytokine that activates the receptor tyrosine kinase KIT and promotes HSC maintenance, how SCF/KIT signaling is regulated in HSCs is poorly understood. The protein tyrosine phosphatase 4A (PTP4A) family (aka PRL [phosphatase of regenerating liver] phosphatases), consisting of PTP4A1/PRL1, PTP4A2/PRL2, and PTP4A3/PRL3, represents an intriguing group of phosphatases implicated in cell proliferation and tumorigenesis. However, the role of PTP4A in hematopoiesis remains elusive. To define the role of PTP4A in hematopoiesis, we analyzed HSC behavior in Ptp4a2 (Prl2) deficient mice. We found that Ptp4a2 deficiency impairs HSC self-renewal as revealed by serial bone marrow transplantation assays. Moreover, we observed that Ptp4a2 null hematopoietic stem and progenitor cells (HSPCs) are more quiescent and show reduced activation of the AKT and ERK signaling. Importantly, we discovered that the ability of PTP4A2 to enhance HSPC proliferation and activation of AKT and ERK signaling depends on its phosphatase activity. Furthermore, we found that PTP4A2 is important for SCF-mediated HSPC proliferation and loss of Ptp4a2 decreased the ability of oncogenic KIT/D814V mutant in promoting hematopoietic progenitor cell proliferation. Thus, PTP4A2 plays critical roles in regulating HSC self-renewal and mediating SCF/KIT signaling

Integrating Growth and Environmental Parameters to Discriminate Powdery Mildew and Aphid of Winter Wheat Using Bi-Temporal Landsat-8 Imagery

Monitoring and discriminating co-epidemic diseases and pests at regional scales are of practical importance in guiding differential treatment. A combination of vegetation and environmental parameters could improve the accuracy for discriminating crop diseases and pests. Different diseases and pests could cause similar stresses and symptoms during the same crop growth period, so combining growth period information can be useful for discerning different changes in crop diseases and pests. Additionally, problems associated with imbalanced data often have detrimental effects on the performance of image classification. In this study, we developed an approach for discriminating crop diseases and pests based on bi-temporal Landsat-8 satellite imagery integrating both crop growth and environmental parameters. As a case study, the approach was applied to data during a period of typical co-epidemic outbreak of winter wheat powdery mildew and aphids in the Shijiazhuang area of Hebei Province, China. Firstly, bi-temporal remotely sensed features characterizing growth indices and environmental factors were calculated based on two Landsat-8 images. The synthetic minority oversampling technique (SMOTE) algorithm was used to resample the imbalanced training data set before model construction. Then, a back propagation neural network (BPNN) based on a new training data set balanced by the SMOTE approach (SMOTE-BPNN) was developed to generate the regional wheat disease and pest distribution maps. The original training data set-based BPNN and support vector machine (SVM) methods were used for comparison and testing of the initial results. Our findings suggest that the proposed approach incorporating both growth and environmental parameters of different crop periods could distinguish wheat powdery mildew and aphids at the regional scale. The bi-temporal growth indices and environmental factors-based SMOTE-BPNN, BPNN, and SVM models all had an overall accuracy high than 80%. Meanwhile, the SMOTE-BPNN method had the highest G-means among the three methods. These results revealed that the combination of bi-temporal crop growth and environmental parameters is essential for improving the accuracy of the crop disease and pest discriminating models. The combination of SMOTE and BPNN could effectively improve the discrimination accuracy of the minor disease or pest

Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors

The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances stem cell factor/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors

MptpB Promotes Mycobacteria Survival by Inhibiting the Expression of Inflammatory Mediators and Cell Apoptosis in Macrophages

Tuberculosis is a severe contagious disease caused by Mycobacterium tuberculosis (Mtb). To develop new vaccines and medicine against TB, there is an urgent need to provide insights into the mechanisms by which Mtb induces tuberculosis. In this study, we found that secreted Mtb virulence factor MptpB significantly enhanced the survival of H37Rv in macrophages. MptpB suppressed the production of iNOS, the expression of inflammatory factors IL-1β and IL-6, as well as the apoptosis of the macrophage in Mtb infected RAW264.7 cells. Mechanism investigation showed that MptpB simultaneously hampered the NF-κB and MAPK signal pathways, evidenced by its blocking of p65, IKKα, Erk1/2, and p38 phosphorylation induced by Mtb infection. MptpB also inhibited host cell p53 expression. The results demonstrated that MptpB contributed to the survival of H37Rv by inhibiting host inflammatory responses and apoptosis through impeding the NF-κB and MAPK signal pathways and p53 expression in the macrophage

A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes

Eukaryotic genes are under the control of regulatory complexes acting through chromatin structure to control gene expression. Here we report the identification of a family of multiprotein corepressor complexes that function through modifying chromatin structure to keep genes silent. The polypeptide composition of these complexes has in common a core of two subunits, HDAC1,2 and BHC110, an FAD-binding protein. A candidate X-linked mental retardation gene and the transcription initiation factor II-I (TFII-I) are components of a novel member of this family of complexes. Other subunits of these complexes include polypeptides associated with cancer causing chromosomal translocations. These findings not only delineate a novel class of multiprotein complexes involved in transcriptional repression but also reveal an unanticipated role for TFII-I in transcriptional repression

Integrating Early Growth Information to Monitor Winter Wheat Powdery Mildew Using Multi-Temporal Landsat-8 Imagery

Powdery mildew is one of the dominant diseases in winter wheat. The accurate monitoring of powdery mildew is important for crop management and production. Satellite-based remote sensing monitoring has been proven as an efficient tool for regional disease detection and monitoring. However, the information provided by single-date satellite scene is hard to achieve acceptable accuracy for powdery mildew disease, and incorporation of early period contextual information of winter wheat can improve this situation. In this study, a multi-temporal satellite data based powdery mildew detecting approach had been developed for regional disease mapping. Firstly, the Lansat-8 scenes that covered six winter wheat growth periods (expressed in chronological order as periods 1 to 6) were collected to calculate typical vegetation indices (VIs), which include disease water stress index (DSWI), optimized soil adjusted vegetation index (OSAVI), shortwave infrared water stress index (SIWSI), and triangular vegetation index (TVI). A multi-temporal VIs-based k-nearest neighbors (KNN) approach was then developed to produce the regional disease distribution. Meanwhile, a backward stepwise elimination method was used to confirm the optimal multi-temporal combination for KNN monitoring model. A classification and regression tree (CART) and back propagation neural networks (BPNN) approaches were used for comparison and validation of initial results. VIs of all periods except 1 and 3 provided the best multi-temporal data set for winter wheat powdery mildew monitoring. Compared with the traditional single-date (period 6) image, the multi-temporal images based KNN approach provided more disease information during the disease development, and had an accuracy of 84.6%. Meanwhile, the accuracy of the proposed approach had 11.5% and 3.8% higher than the multi-temporal images-based CART and BPNN models&rsquo;, respectively. These results suggest that the use of satellite images for early critical disease infection periods is essential for improving the accuracy of monitoring models. Additionally, satellite imagery also assists in monitoring powdery mildew in late wheat growth periods