Influence of the Mega-Urban Heat Island on Spatial Transfer of Summer Thermal Comfort: Evidence from Tianjin, China

Human thermal comfort in urban spaces deteriorates as rapid urbanization proceeds. However, effective tests and discoveries of spatial statistic patterns are currently absent. This study collected remote sensing images and measured meteorological data of the summers of 1992–2017, Tianjin of China and aims to clarify patterns of spatial transfer and thermal comfort changes caused by a mega-UHI (Urban Heat Island). An analytic transfer matrix and the spatial autocorrelation were developed to study spatial pattern changes and features of the spatial transfer of thermal comfort caused by UHI. Results show these patterns in the affected areas can be divided into different levels: patterns of low-level affected areas transferred by circular expansion into block-mass jumping, while the position of high-level affected areas remains stable. The spatial transfer of thermal comfort in the affected areas shows two apparent stages: the transfer from areas of high-density and low-storied buildings and into areas of multiple storied buildings, and transfer from areas of low and multiple storied buildings into those of high storied buildings. This implies changes in urban planning can guide spatial, structural, and functional evolution. The study identifies features of spatial change and spatial patterns related to the influence of Mega-UHI on thermal comfort

Seneca Valley Virus 2C and 3Cpro Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway

Seneca Valley virus (SVV) is the only member of the genus Senecavirus of the Picornaviridae family. SVV can selectively infect and lyse tumor cells with neuroendocrine features and is used as an oncolytic virus for treating small-cell lung cancers. However, the detailed mechanism underlying SVV-mediated destruction of tumor cells remains unclear. In this study, we found that SVV can increase the proportion of apoptotic 293T cells in a dose- and time-dependent manner. SVV-induced apoptosis was initiated via extrinsic and intrinsic pathways through activation of caspase-3, the activity of which could be attenuated by a pan-caspase inhibitor (Z-VAD-FMK). We confirmed that SVV 2C and 3Cpro play critical roles in SVV-induced apoptosis. The SVV 2C protein was located solely in the mitochondria and activated caspase-3 to induce apoptosis. SVV 3Cpro induced apoptosis through its protease activity, which was accompanied by release of cytochrome C into the cytoplasm, but did not directly cleave PARP1

Japanese Encephalitis Virus wild strain infection suppresses dendritic cells maturation and function, and causes the expansion of regulatory T cells

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) accounts for acute illness and death. However, few studies have been conducted to unveil the potential pathogenesis mechanism of JEV. Dendritic cells (DCs) are the most prominent antigen-presenting cells (APCs) which induce dual humoral and cellular responses. Thus, the investigation of the interaction between JEV and DCs may be helpful for resolving the mechanism of viral escape from immune surveillance and JE pathogenesis.</p> <p>Results</p> <p>We examined the alterations of phenotype and function of DCs including bone marrow-derived DCs (bmDCs) <it>in vitro </it>and spleen-derived DCs (spDCs) <it>in vivo </it>due to JEV P3 wild strain infection. Our results showed that JEV P3 infected DCs <it>in vitro </it>and <it>in vivo</it>. The viral infection inhibited the expression of cell maturation surface markers (CD40, CD80 and CD83) and MHCⅠ, and impaired the ability of P3-infected DCs for activating allogeneic naïve T cells. In addition, P3 infection suppressed the expression of interferon (IFN)-α and tumor necrosis factor (TNF)-α but enhanced the production of chemokine (C-C motif) ligand 2 (CCL2) and interleukin (IL)-10 of DCs. The infected DCs expanded the population of CD4+ Foxp3+ regulatory T cell (Treg).</p> <p>Conclusion</p> <p>JEV P3 infection of DCs impaired cell maturation and T cell activation, modulated cytokine productions and expanded regulatory T cells, suggesting a possible mechanism of JE development.</p

African swine fever virus pA104R protein acts as a suppressor of type I interferon signaling

This study evaluates the role of the late viral protein, pA104R, in African swine fever virus immunosuppression. ASFV-encoded pA104R is a putative histone-like protein that is highly conserved throughout different virulent and non-virulent isolates. Previous studies have demonstrated that pA104R plays a vital role in the ASFV replication cycle and is a potential target for antiviral therapy. Here, we demonstrated that pA104R is a potent antagonist of type I interferon signaling. IFN-stimulated response element activity and subsequent transcription of co-transfected and endogenous interferon-stimulated genes were attenuated by pA104R treatment in HEK-293 T cells. Immunoprecipitation assay and reciprocal pull-down showed that pA104R does not interact directly with STAT1, STAT2, or IRF9. However, pA104R could inhibit IFN signaling by attenuating STAT1 phosphorylation, and we identified the critical amino acid residues (R/H69,72 and K/R92,94,97) involved through the targeted mutation functional assays. Although pA104R is a histone-like protein localized to the nucleus, it did not inhibit IFN signaling through its DNA-binding capacity. In addition, activation of the ISRE promoter by IRF9-Stat2(TA), a STAT1-independent pathway, was inhibited by pA104R. Further results revealed that both the transcriptional activation and recruitment of transcriptional stimulators by interferon-stimulated gene factor 3 were not impaired. Although we failed to determine a mechanism for pA104R-mediated IFN signaling inhibition other than attenuating the phosphorylation of STAT1, these results might imply a possible involvement of epigenetic modification by ASFV pA104R. Taken together, these findings support that pA104R is an antagonist of type I interferon signaling, which may interfere with multiple signaling pathways

1,1-Dimethyl­hydrazin-1-ium picrate

In the title compound, C2H9N2 +·C6H2N3O7 −, the dihedral angles between the mean planes of the three nitro groups and the benzene ring are 63.5 (3), 10.5 (2) and 10.4 (2)°. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds into a two-dimensional network parallel to (001)

Attenuation of Mycoplasma hyopneumoniae Strain ES-2 and Comparative Genomic Analysis of ES-2 and Its Attenuated Form ES-2L

Mycoplasma hyopneumoniae causes swine respiratory disease worldwide. Due to the difficulty of isolating and cultivating M. hyopneumoniae, very few attenuated strains have been successfully isolated, which hampers the development of attenuated vaccines. In order to produce an attenuated M. hyopneumoniae strain, we used the highly virulent M. hyopneumoniae strain ES-2, which was serially passaged in vitro 200 times to produce the attenuated strain ES-2L, and its virulence was evidenced to be low in an animal experiment. In order to elucidate the mechanisms underlying virulence attenuation, we performed whole-genome sequencing of both strains and conducted comparative genomic analyses of strain ES-2 and its attenuated form ES-2L. Strain ES-2L showed three large fragment deletion regions including a total of 18 deleted genes, compared with strain ES-2. Analysis of single-nucleotide polymorphisms (SNPs) and indels indicated that 22 dels were located in 19 predicted coding sequences. In addition to these indels, 348 single-nucleotide variations (SNVs) were identified between strains ES-2L and ES-2. These SNVs mapped to 99 genes where they appeared to induce amino acid substitutions and translation stops. The deleted genes and SNVs may be associated with decreased virulence of strain ES-2L. Our work provides a foundation for further examining virulence factors of M. hyopneumoniae and for the development of attenuated vaccines

Isolation of Mycobacterium tuberculosis complex (MTBC) from dairy cows in China

Eleven thousand five hundred and eighty non-blood samples from dairy cows were subjected to mycobacterium culture and genotyping. As a result, a total of 142 isolates of Mycobacterium tuberculosis complex (MBTC) were identified. Among them, 65 were Mycobacterium tuberculosis, while 77 Mycobacterium bovis. The genotype of M. tuberculosis strains was mainly Beijing family. In addition, the isolation rates of MTBC were 33.89% for lung lymph nodes, 2.81% for nasal swabs, and 3.95% for pharyngeal swabs from cattle positive to tuberculin skin test, respectively. This evidence implied that M. tuberculosis infection in cattle is a new risk to public health and should be paid more attention.Key words: Mycobacterium tuberculosis complex, cows, tuberculosis, zoonosis

Transactivated Epidermal Growth Factor Receptor Recruitment of α-actinin-4 From F-actin Contributes to Invasion of Brain Microvascular Endothelial Cells by Meningitic Escherichia coli

Bacterial penetration of the blood-brain barrier requires its successful invasion of brain microvascular endothelial cells (BMECs), and host actin cytoskeleton rearrangement in these cells is a key prerequisite for this process. We have reported previously that meningitic Escherichia coli can induce the activation of host's epidermal growth factor receptor (EGFR) to facilitate its invasion of BMECs. However, it is unknown how EGFR specifically functions during this invasion process. Here, we identified an important EGFR-interacting protein, α-actinin-4 (ACTN4), which is involved in maintaining and regulating the actin cytoskeleton. We observed that transactivated-EGFR competitively recruited ACTN4 from intracellular F-actin fibers to disrupt the cytoskeleton, thus facilitating bacterial invasion of BMECs. Strikingly, this mechanism operated not only for meningitic E. coli, but also for infections with Streptococcus suis, a Gram-positive meningitis-causing bacterial pathogen, thus revealing a common mechanism hijacked by these meningitic pathogens where EGFR competitively recruits ACTN4. Ever rising levels of antibiotic-resistant bacteria and the emergence of their extended-spectrum antimicrobial-resistant counterparts remind us that EGFR could act as an alternative non-antibiotic target to better prevent and control bacterial meningitis

Comparative genomic analyses of Mycoplasma hyopneumoniae pathogenic 168 strain and its high-passaged attenuated strain

Background: Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia (EP), a mild, chronic pneumonia of swine. Despite presenting with low direct mortality, EP is responsible for major economic losses in the pig industry. To identify the virulence-associated determinants of M. hyopneumoniae, we determined the whole genome sequence of M. hyopneumoniae strain 168 and its attenuated high-passage strain 168-L and carried out comparative genomic analyses. Results: We performed the first comprehensive analysis of M. hyopneumoniae strain 168 and its attenuated strain and made a preliminary survey of coding sequences (CDSs) that may be related to virulence. The 168-L genome has a highly similar gene content and order to that of 168, but is 4,483 bp smaller because there are 60 insertions and 43 deletions in 168-L. Besides these indels, 227 single nucleotide variations (SNVs) were identified. We further investigated the variants that affected CDSs, and compared them to reported virulence determinants. Notably, almost all of the reported virulence determinants are included in these variants affected CDSs. In addition to variations previously described in mycoplasma adhesins (P97, P102, P146, P159, P216, and LppT), cell envelope proteins (P95), cell surface antigens (P36), secreted proteins and chaperone protein (DnaK), mutations in genes related to metabolism and growth may also contribute to the attenuated virulence in 168-L. Furthermore, many mutations were located in the previously described repeat motif, which may be of primary importance for virulence. Conclusions: We studied the virulence attenuation mechanism of M. hyopneumoniae by comparative genomic analysis of virulent strain 168 and its attenuated high-passage strain 168-L. Our findings provide a preliminary survey of CDSs that may be related to virulence. While these include reported virulence-related genes, other novel virulence determinants were also detected. This new information will form the foundation of future investigations into the pathogenesis of M. hyopneumoniae and facilitate the design of new vaccines

C500 variants conveying complete mucosal immunity against fatal infections of pigs with Salmonella enterica serovar Choleraesuis C78-1 or F18+ Shiga toxin-producing Escherichia coli

Salmonella enterica serovar Choleraesuis (S. Choleraesuis) C500 strain is a live, attenuated vaccine strain that has been used in China for over 40 years to prevent piglet paratyphoid. However, this vaccine is limited by its toxicity and does not offer protection against diseases caused by F18+ Shiga toxin-producing Escherichia coli (STEC), which accounts for substantial economic losses in the swine industry. We recently generated a less toxic derivative of C500 strain with both asd and crp deletion (S. Choleraesuis C520) and assessed its efficacy in mice. In addition, we demonstrate that C520 is also less toxic in pigs and is effective in protecting pigs against S. Choleraesuis when administered orally. To develop a vaccine with a broader range of protection, we prepared a variant of C520 (S. Choleraesuis C522), which expresses rSF, a fusion protein comprised of the fimbriae adhesin domain FedF and the Shiga toxin-producing IIe B domain antigen. For comparison, we also prepared a control vector strain (S. Choleraesuis C521). After oral vaccination of pigs, these strains contributed to persistent colonization of the intestinal mucosa and lymphoid tissues and elicited both cytokine expression and humoral immune responses. Furthermore, oral immunization with C522 elicited both S. Choleraesuis and rSF-specific immunoglobulin G (IgG) and IgA antibodies in the sera and gut mucosa, respectively. To further evaluate the feasibility and efficacy of these strains as mucosal delivery vectors via oral vaccination, we evaluated their protective efficacy against fatal infection with S. Choleraesuis C78-1, as well as the F18+ Shiga toxin-producing Escherichia coli field strain Ee, which elicits acute edema disease. C521 conferred complete protection against fatal infection with C78-1; and C522 conferred complete protection against fatal infection with both C78-1 and Ee. Our results suggest that C520, C521, and C522 are competent to provide complete mucosal immune protection against fatal infection with S. Choleraesuis in swine and that C522 equally qualifies as an oral vaccine vector for protection against F18+ Shiga toxin-producing Escherichia coli