Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer

Background: Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. Virus entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retroviruses, the JSRV Env protein is also a potent oncoprotein and is responsible for lung cancer in animals. Of concern, Hyal2 is a functional receptor for JSRV in humans. Results: We show here that JSRV is fully capable of infecting human cells, as measured by its reverse transcription and persistence in the DNA of cultured human cells. Several studies have indicated a role for JSRV in human lung cancer while other studies dispute these results. To further investigate the role of JSRV in human lung cancer, we used highly-specific mouse monoclonal antibodies and a rabbit polyclonal antiserum against JSRV Env to test for JSRV expression in human lung cancer. JSRV Env expression was undetectable in lung cancers from 128 human subjects, including 73 cases of bronchioalveolar carcinoma (BAC; currently reclassified as lung invasive adenocarcinoma with a predominant lepidic component), a lung cancer with histology similar to that found in JSRV-infected sheep. The BAC samples included 8 JSRV DNA-positive samples from subjects residing in Sardinia, Italy, where sheep farming is prevalent and JSRV is present. We also tested for neutralizing antibodies in sera from 138 Peruvians living in an area where sheep farming is prevalent and JSRV is present, 24 of whom were directly exposed to sheep, and found none. Conclusions: We conclude that while JSRV can infect human cells, JSRV plays little if any role in human lung cancer

Integrative analysis of different low-light-tolerant cucumber lines in response to low-light stress

IntroductionLow light stress inhibits plant growth due to a line of physiological disruptions in plants, and is one of the major barriers to protected cucumber cultivation in northern China.MethodsTo comprehensively understand the responses of cucumber seedlings to low-light stress, the low-light-tolerant line (M67) and The low-light-sensitive line (M14) were conducted for the analysis of photosynthetic phenotype, RNA sequencing (RNA-seq) and the expression level of photosynthesis-related genes in leaves under low-light stress and normal light condition (control).ResultsThe results showed that there was a sharp decrease in the photosynthate accumulation in the leaves of the sensitive line, M14, resulting in a large decrease in the photosynthetic rate (Pn) (with 31.99%) of leaves compared to that of the control, which may have been caused by damage to chloroplast ultrastructure or a decrease in chlorophyll (Chl) content. However, under the same low-light treatment, there was no large drop in the photosynthate accumulation and even no decrease in Pn and Chl content for the tolerant line, M67. Moreover, results of gene expression analysis showed that the expression level of genes CsPsbQ (the photosystem II oxygen-evolving enhancer protein 3 gene) and Csgamma (ATPase, F1 complex gene) in the M14 leaves decreased sharply (by 35.04% and 30.58%, respectively) compared with the levels in the M67 leaves, which decreased by 14.78% and 23.61%, respectively. The expression levels of genes involved in Chl synthesis and carbohydrate biosynthesis in the leaves of M14 decreased markedly after low-light treatment; in contrast, there were no sharp decreases or changes in leaves of M67.DiscussionOver all, the ability of cucumber to respond to low-light stress, as determined on the basis of the degree of damage in leaf structure and chloroplast ultrastructure, which corresponded to decreased gene expression levels and ATP phosphorylase activity, significantly differed between different low-light-tolerant lines, which was manifested as significant differences in photosynthetic capacity between them. Results of this study will be a reference for comprehensive insight into the physiological mechanism involved in the low-light tolerance of cucumber

Critical Epitopes in the Nucleocapsid Protein of SFTS Virus Recognized by a Panel of SFTS Patients Derived Human Monoclonal Antibodies

BACKGROUND: SFTS virus (SFTSV) is a newly discovered pathogen to cause severe fever with thrombocytopenia syndrome (SFTS) in human. Successful control of SFTSV epidemic requires better understanding of the antigen target in humoral immune responses to the new bunyavirus infection. METHODOLOGY/PRINCIPAL FINDINGS: We have generated a combinatorial Fab antibody phage library from two SFTS patients recovered from SFTSV infection. To date, 94 unique human antibodies have been generated and characterized from over 1200 Fab antibody clones obtained by screening the library with SFTS purified virions. All those monoclonal antibodies (MAbs) recognized the nucleocapsid (N) protein of SFTSV while none of them were reactive to the viral glycoproteins Gn or Gc. Furthermore, over screening 1000 mouse monoclonal antibody clones derived from SFTSV virions immunization, 462 clones reacted with N protein, while only 16 clones were reactive to glycoprotein. Furthermore, epitope mapping of SFTSV N protein was performed through molecular simulation, site mutation and competitive ELISA, and we found that at least 4 distinct antigenic epitopes within N protein were recognized by those human and mouse MAbs, in particular mutation of Glu10 to Ala10 abolished or significantly reduced the binding activity of nearly most SFTS patients derived MAbs. CONCLUSIONS/SIGNIFICANCE: The large number of human recombinant MAbs derived from SFTS patients recognized the viral N protein indicated the important role of the N protein in humoral responses to SFTSV infection, and the critical epitopes we defined in this study provided molecular basis for detection and diagnosis of SFTSV infection

Adaptability of skeletal muscle to hormone treatment in relation to gender and aging

The aims of this study were to investigate the expression of myosin isoforms, muscle contractility at the cell level, and changes in these parameters in response to altered hormonal status in aging male and female rodents. In addition, by using mice lacking thyroid hormone receptors (TR[alpha]1 or TR[beta] or TR[alpha]1/[beta]) we tried to improve our understanding of the mechanisms by which thyroid hormone regulates the expression of specific MyHC isoforms via these different nuclear receptors. The enzyme-histochemical characteristics showed that 4 weeks of l treatment induced a significant decrease in the number of type I fibers and an increase in the number of type IC and IIC fibers in the soleus, irrespective of gender and age. In the EDL, T3 treatment resulted in a significant type IIA to type IIB fiber transition in both young and old female rats, but no changes were observed in the male rats. TR[alpha]1-/- or TR[alpha]1- /-[beta]-/-mice significantly increased the number of type I fibers and decreased type IIA fibers. The proportions of type I and type IIA fibers did not change in TR[beta] -/- mice. High-sensitive 7% SDS-PAGE analysis of MyHC isoform composition confirmed and extended the enzyme-histochemical results. That is, a significant down-regulation of the type I MyHC and an up-regulation of type IIA MyHC were observed in muscles from hyperthyroid rats, irrespective of gender. However, the upregulation of the IIX MyHC was more pronounced in male than in female rats both at the single-fiber and whole-muscle levels, irrespective of age. The expression of MyHC isoforms in females was more variable than that in males, i.e., type IIAX fibers, type I/IIAX fibers, [alpha] cardiac-like fibers and [alpha] cardiac-like/IIA fibers were found. In the EDL, the age-related type IIB to IIX MyHC isoform switching was found in both male and female rats, i.e., the type IIX MyHC content was higher and the type IIB content lower in old rats of both sexes. In the females, T3 treatment decreased the type IIA MyHC content and increased type IIB MyHC content in both young and old rats. In the males, on the other hand, T3 treatment had no significant influence on the expression of the different fast MyHC isoforms, in spite of the fact that type IIA mRNA has been reported to be downregulated in both males and females. The different expression of MyHCs in the EDL muscle of males and females in response to T3 treatment raises the possibility of a gender-related difference in the translational regulation of MyHC isoforms by thyroid hormone. At the single-fiber level, an age-related slowing of maximum velocity of unloaded shortening (V0) was observed in the soleus muscle of rats in both genders. Four weeks of T3 treatment induced a stronger upregulation of the fast MyHC IIA, MyLCf1 and MyLCf2 isoforms from soleus muscle fibers in females than in those of males. Concomitantly, the V0 of the pooled fibers was higher in female than in male hyperthyroid rats regardless of animal age in soleus fibers. Further, in the female hyperthyroid rats, V0 of the fibers expressing [beta]/slow (type I) MyHC was significantly higher, compared with those in control rats of both the young and the old; the differences between male and female hyperthyroid soleus muscles are suggested to be related to an interaction of thyroid hormone and sex hormones in the regulation of myosin gene expression. Disuption of thyroid hormone receptors TR[alpha]1 or TR[beta] or both receptors induced transitions of MyHC isoforms; i.e., in EDL muscle, the TR deficiency induced a significant decrease in type IIB MyHC. In the soleus, a significant up-regulation of type I MyHC and a down-regulation of type IIA MyHC were observed in TR[alpha]1-/-[beta]-/- and TR[alpha]1-/- mice. The extent of the deficient effect was highly dependent on the type of receptor deleted. The lack of TR[beta] had no significant effect on the expression of MyHC isoforms. A moderate type I MyHC increase was observed in the TR[alpha]1-/-mice, while a dramatic over-expression of the slow myosin isoform (type I MyHC), and a corresponding down-regulation of the fast type IIA MyHC were observed in TR[alpha]1-/-[beta]-/- mice. Embryonic or fetal MyHC isoforms were not expressed in either soleus or EDL from different TR deficient mice, indicating that the developmental transition from embryonic or fetal MyHC isoforms is not solely related to an effect of T3 via TRs. These results suggest that either TR[alpha]1 or TR[beta] is able to functionally substitute for, or co-operate with, each other, and emphasize the complex interaction between TRs and other cell- and muscle-type specific factors, which play a very important role in the developmental transition from embryonic or fetal MyHC to adult MyHC isoforms

Gender- and age-related differences in the regulatory influence of thyroid hormone on the contractility and myosin composition of single rat soleus muscle fibres

The effects of 4 weeks of thyroid hormone (3,5,3'-triiodothyronine, T3) treatment on the myosin isoform composition and maximum velocity of unloaded shortening (V0) of single soleus muscle fibres of young (3-6 months) and old (20-24 months) female (149 fibres) and male (200 fibres) rats were studied. Gender-related differences in the up-regulation of fast myosin heavy chain (MyHC) and myosin light chain (MyLC) isoforms were observed. In the female hyperthyroid rats, pure type I fibres and fibres co-expressing type I and type IIA MyHC (type I/IIA fibres) predominated. Some fibres expressed an alpha cardiac-like MyHC isoform either purely (alpha cardiac-like fibre type) or in co-expression with IIA MyHC (alpha cardiac-like/IIA fibre type). In the male hyperthyroid rats, on the other hand, all fibres were either type I/IIA or type I/IIAX. The relative quantities of fast MyLC isoforms in type I/IIA and type I/IIAX fibres was higher in female than in male hyperthyroid rats. V0 was similar in male and female control rats, and decreased with age in both genders (P<0.001). After T3 treatment, the average V0 increased (P<0.001) in females with a concomitant up-regulation of fast MyHC and fast MyLC isoforms irrespective of age. The average V0 of the pooled fibres was higher (P<0.001) in female than in male hyperthyroid rats at both ages. In conclusion, gender- and age-related differences were observed in the regulatory influence of 4 weeks' T3 treatment on myosin isoform composition and V0 in soleus fibres. These differences are presumably related to an interaction of thyroid and sex hormones in the regulation of myosin gene expression

Flow cytometric observation of picophytoplankton community structure in the cascade reservoirs along the Wujiang River, SW China

Picophytoplankton community structure has been seasonally investigated in the cascade reservoirs along the Wujiang River from April 2006 to January 2007. Besides picoeukaryotes, two groups of picocyanobacteria have also been detected by flow cytometry. One is a phycoerythrin-rich picocyanobacteria (PE-rich Pcy), the other is a red-fluorescing cells with lacking orange fluorescence and could be a phycocyanin-rich picocyanobacteria (PC-rich Pcy). The average abundances of PC-rich Pcy, PE-rich Pcy and picoeukaryotes were 103, 104 and 102 cells mL-1, respectively. PE-rich Pcy was the dominant population but showed a reduction with eutrophication, and therefore the community structure of picophytoplankton transformed from dominant PE-rich Pcy to dominant PE-rich Pcy and PC-rich Pcy, which suggested they are excellent indicators for the change of trophic state. Picophytoplankton community structure also presented a seasonal variation, indicating the different response of each picophytoplankton group to water temperature

A novel physics-informed framework for real-time adaptive modal parameters estimation of offshore structures

Singular value decomposition provides a rigorous mathematical foundation for these monitoring methods, such as modal analysis, damage detection, etc. As substantial limitations including computational efficiency and adaptive capabilities have been identified in the matrix process, data-driven algorithms with enhanced efficiency and accuracy to adapt the rapid development of information and technologies have been highly required in offshore structures monitoring. To meet this demand, a novel physics-informed frame work enabling the real-time adaptive monitoring has been proposed in this paper. The working principle of the developed framework has been represented by the smart conversion of physics-informed modal identification into the optimal process of fast and accurate solving an eigensystem governed by differential equations via recurrent neural network. The ingenious design of the proposed framework has complied with the rule of singular value decomposition used for modal identification and therefore, learning capabilities of the physics-informed framework have been remarkably enhanced by successfully addressing two bottleneck problems including proper initialized input values and the optimal time increment of the developed recurrent neural network. Both numerical simulations and the field-data based study of a mono-pile offshore wind turbine structure have been presented to examine the superior performance of the proposed framework. Results have shown that the proposed framework has the ability to adaptively identify modal parameters with a higher level of computational efficiency as compared with traditional methods. Furthermore, the computational advantage of the develop framework has demonstrated the potential to integrate with sensor networks and edge computing for smart monitoring and maintenance in various engineering subjects

Seismic Data Query Algorithm Based on Edge Computing

Edge computing can reduce the transmission pressure of wireless networks in earthquakes by pushing computing functionalities to network edges and avoiding the data transmission to cloud servers. However, this also leads to the scattered storage of data content in each edge server, increasing the difficulty of content search. This paper investigates the seismic data query problem supported by edge computing. We first design a lookup mechanism based on bloom filter, which can quickly determine if there is the information that we need on a particular edge server. Then, the MEC-based data query problem is formulated as an optimization problem whose goal is to minimize the long-term average task delay with the constraints of computing capacity of edge servers. To reduce the complexity of problem, we further transform it as a Markov Decision Process by defining state space, action space and reward function. A novel DQN-based seismic data query algorithm is proposed to solve problem effectively. Extensive simulation-based testing shows that the proposed algorithm performances better when compared with two state-of-the-art solutions

Field Data Observations for Monitoring the Impact of Typhoon "In-fa" on Dynamic Performances of Mono-pile Offshore Wind Turbines: A Novel Systematic Study

For offshore structures such as offshore wind turbines (OWT), typhoon is usually considered one of the most critical threats to structural safety performances and service life due to its heavy wind, wave, and even coexisted storm surge. Meanwhile, it is challenging to obtain the systematic data from the environmental conditions, structural dynamic vibrations and the SCADA record, when typhoon passes by the offshore wind farm. Taking into account these situations, a real-time multi-source monitoring system enabling the investigation of the typhoon impact on the performances of OWT, has been firstly established and implemented to a 4.0 MW mono-pile OWT in Rudong, Jiangsu, China. One of the major contributions in this work is to develop the monitoring system using a unique environment of real-world data that has been synchronously obtained from waves, winds, vibrational accelerations, inclinations of towers and SCADA data during the typhoon ”In-fa” passing by the wind farm, and provide the scientific community with the underlying standards and technical recommendations. To investigate the influence caused by ”In-fa”, comparison results of the measured data in the range of June to August have been analysed. It is worth noting that two conclusions have been obtained: 1) the region near the nacelle is not always the most critical vibrational area. Actually, the change of the maximum structural response in the position under different external loads should be applied to effectively evaluate the structural safety; 2) the measured accelerations exhibit an obvious decay process in the presence of the turbine rotor-stop, but not the yaw rigid-body motion. This observation promotes the accurate identification of modal parameters for the long-term monitoring. Consequently, these valuable findings to facilitate the assessment of structural operational conditions have been developed into two guide-lines. All the data and analyses presented in this paper provide a valuable insight into the design, energy efficiency, safety monitoring and damage diagnosis of OWT structures