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

Effects of High-Grain Diet With Buffering Agent on the Hepatic Metabolism in Lactating Goats

To gain insight on the effects of a high-grain diet with buffering agent on liver metabolism and the changes of plasma biochemical parameters and amino acids in hepatic vein and portal vein, commercial kit and high performance liquid chromatography (HPLC) were applied to determine the concentration of amino acids of hepatic vein and portal vein blood samples, quantitative real-time PCR and comparative proteomic approach was employed to investigate proteins differentially expressed in liver in lactating dairy goats feeding high-grain diet with buffering agent or only high-grain diet. Results showed that feeding high-grain diet with buffering agent to lactating dairy goats could outstanding increase amino acid content of Gln (p < 0.01), and the amino acid contents of Arg and Tyr in BG were significantly higher (p < 0.05) than that in HG. After adding the buffering agent, the metabolism of amino acids in the liver were changed and most of the amino acids were increasingly synthesized and decreasingly consumed in the liver. In addition, 46 differentially expressed protein spots (≥1.5-fold changed) were detected in buffering group vs. control group using 2-DE technique and MALDI-TOF/TOF proteomics analyzer. Of these, 24 proteins showed increased expression and 22 proteins showed decreased expression in the buffer group vs. control group. Data on Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the high-grain diet with buffering agent alter the expression of proteins related to amino acids metabolism and glycometabolism. In addition, the results conclude that feeding high-grain diet with buffering agent can strengthen anti-oxidant capacity, stress ability, slow down urea metabolism, and alter amino acid metabolism as well as glycometabolism in the liver through different detection methods including proteomic analysis, real-time PCR analysis and biochemical analysis

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

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

Numerical simulation study on the effects of liquid water atomization on the flow field and performance of aluminum-based water ramjet engines

In order to investigate the effects of different water inlet droplet diameters on the performance of aluminum-based water ramjet engines, the internal flow field of the engine was analyzed through numerical simulation. The results showed that by selecting a suitable water droplet diameter at the water inlet and controlling the time required for water droplet evaporation and heat absorption, the working range of aluminum-water combustion reaction can be expanded and the specific impulse of the engine can be increased. In engine design and practical application, the design of the water injection nozzle upstream of the engine is critical, and the droplet diameter at the water inlet should be controlled within a suitable range. A diameter that is too large will reduce the evaporation efficiency and hinder the further diffusion of combustion reaction. Droplet sizes that are too small will rapidly evaporate, causing the temperature in the flow field to decrease rapidly, leading to a large range of low-temperature regions in the main reaction zone of the combustion chamber, thereby reducing the overall aluminum-water reaction rate of the engine. In addition, the variation of droplet diameter in the downstream water atomization nozzle has little effect on the aluminum-water reaction in the main combustion zone. However, reducing the droplet diameter can facilitate the downstream diffusion of the combustion reaction, further expanding the combustion range and increasing the specific impulse. Furthermore, it can also reduce the temperature near the wall, which is beneficial for reducing the overall thermal protection requirements of the engine

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

Predictors of Condom Use among Peer Social Networks of Men Who Have Sex with Men in Ghana, West Africa

Ghanaian men who have sex with men (MSM) have high rates of HIV infection. A first step in designing culturally relevant prevention interventions for MSM in Ghana is to understand the influence that peer social networks have on their attitudes and behaviors. We aimed to examine whether, in a sample of Ghanaian MSM, mean scores on psychosocial variables theorized to influence HIV/STI risk differed between peer social networks and to examine whether these variables were associated with condom use. We conducted a formative, cross-sectional survey with 22 peer social networks of MSM (n = 137) in Ghana. We assessed basic psychological- needs satisfaction, HIV/STI knowledge, sense of community, HIV and gender non-conformity stigmas, gender equitable norms, sexual behavior and condom use. Data were analyzed using analysis of variance, generalized estimating equations, and Wilcoxon two sample tests. All models were adjusted for age and income, ethnicity, education, housing and community of residence. Mean scores for all psychosocial variables differed significantly by social network. Men who reported experiencing more autonomy support by their healthcare providers had higher odds of condom use for anal (AOR = 3.29, p \u3c 0.01), oral (AOR = 5.06, p \u3c 0.01) and vaginal (AOR = 1.8, p \u3c 0.05) sex. Those with a stronger sense of community also had higher odds of condom use for anal sex (AOR = 1.26, p \u3c 0.001). Compared to networks with low prevalence of consistent condom users, networks with higher prevalence of consistent condom users had higher STD and HIV knowledge, had norms that were more supportive of gender equity, and experienced more autonomy support in their healthcare encounters. Healthcare providers and peer social networks can have an important influence on safer-sex behaviors in Ghanaian MSM. More research with Ghanaian MSM is needed that considers knowledge, attitudes, and norms of their social networks in the development and implementation of culturally relevant HIV/STI prevention intervention strategies

The protective effects of beta-casomorphin-7 against glucose -induced renal oxidative stress in vivo and vitro.

Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The present study aimed to investigate the effect of β-casomorphin-7 (BCM7) on the oxidative stress occurring in kidney tissue in streptozotocin (STZ)-induced diabetic rats and proximal tubular epithelial cells (NRK-52E) exposure to high glucose (HG) by using biochemical methods. There is a significant decrease in plasma insulin and a significant increase in plasma glucagon in the rats of diabetic group. Oral administration of BCM7 for 30 days to rats with STZ-induced diabetes resulted in a significant increase in serum level of insulin, and a decrease in the level of glucagon. Moreover, rats with STZ-induced diabetes had lower levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidative capacity (T-AOC), higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the kidney than that in the control rats. The administration of BCM7 altered the changes of SOD, GPx, T-AOC, MDA and H2O2 in the kidney of diabetic rats. Furthermore, BCM7 alleviated high glucose-induced decreasement in SOD and GPx activity, increasement in MDA contents in the NRK-52E cells. BCM7 ameliorated the changes of angiotensin converting enzyme (ACE) and ACE2 levels in the kidney of diabetic rats and BCM7 lowered the levels of angiotensin (Ang)II in the kidney of diabetic rats and culture medium for cells. Moreover losartan (antagonist of angiotensin II type I receptor) lowered the high glucose-induced oxidative stress in the NRK-52E cells. Our results suggest that administration of BCM7 would alleviate high glucose-induced renal oxidative stress in vivo and in vitro, which may be associated with down regulation of the concentration of Ang II partly