Immune Evasion Strategies of Pre-Erythrocytic Malaria Parasites

Malaria is a mosquito-borne infectious disease of humans. It begins with a bite from an infected female Anopheles mosquito and leads to the development of the pre-erythrocytic and blood stages. Blood-stage infection is the exclusive cause of clinical symptoms of malaria. In contrast, the pre-erythrocytic stage is clinically asymptomatic and could be an excellent target for preventive therapies. Although the robust host immune responses limit the development of the liver stage, malaria parasites have also evolved strategies to suppress host defenses at the pre-erythrocytic stage. This paper reviews the immune evasion strategies of malaria parasites at the pre-erythrocytic stage, which could provide us with potential targets to design prophylactic strategies against malaria

The Prevalence of <i>Escherichia coli</i> Derived from Bovine Clinical Mastitis and Distribution of Resistance to Antimicrobials in Part of Jiangsu Province, China

Bovine mastitis is often taken as one of the most common diseases in dairy farms, which its pathophysiology leads to a reduction of milk production and its quality. The penetration of pathogenic bacteria into the mammary gland, through either a contagious or environmental approach, has been determined the way of infection. The mastitis derived bacteria have become a challenge in practice, since the increasing exposure of antimicrobial. In order to identify characteristics of the epidemiological regulation and drug resistance of the pathogenic bacteria of bovine mastitis in northern Jiangsu, 156 clinical mastitis milk samples were collected from 3 large-scale farms for the epidemiological investigation and analysis of the drug resistance of E. coli. The bacteria were positively isolated in a total of 143 milk samples. The results showed that 78 strains of E. coli were detected, with a prevalence rate of 26.99%, followed by 67 strains of K. pneumoniae, with a prevalence of 23.19%, and 38 strains of Staphylococcus, with a prevalence of spp. 13.15%. In addition, 78 strains of E. coli isolated from bovine mastitis were tested for susceptibility to 8 kinds of antibiotics. It was shown that gentamicin and tetracycline were the most effective against E. coli, with the susceptibility rate of 83.3%, followed by streptomycin and ciprofloxacin, with 73.1% and 71.8% respectively. However, β-lactams including penicillin, cefothiophene, and amoxicillin showed serious resistance to E. coli isolates. There were 12 drug resistance genes detected by PCR, including β-lactam (blaTEM, blaCTX-M, and blaSHV), aminoglycoside (armA and armB), tetracycline (tetA, tetB, and tetC), and quinolone (qnrS, qepA, oqxA, and oqxB) related genes. Notably, all E. coli isolates carried blaTEM gene (100%). The detection rate of blaCTX-M was 53.8%, followed by the detection of blaSHV (20.5%), armA (9.0%), tetA (26.9%), tetB (2.6%), tetC (20.5%), qnrS (29.5%), oqxA (37.2%) and oqxB (1.3%). The present study provides crucial information on the distribution of bovine mastitis derived bacterial pathogens in Jiangsu province, as well as highlighting the antimicrobial resistance which might help to improve the efficiency of antibiotics treatment on bovine mastitis

The Inhibition of LPS-Induced Oxidative Stress and Inflammatory Responses Is Associated with the Protective Effect of (-)-Epigallocatechin-3-Gallate on Bovine Hepatocytes and Murine Liver

This study aimed to evaluate whether (-)-epigallocatechin-3-gallate (EGCG) alleviates hepatic responses to lipopolysaccharide (LPS)-induced inflammation and oxidation. Isolated bovine hepatocytes and BALB/c mice were used for LPS challenge and EGCG pretreatment experiments in vitro and in vivo. LPS-challenged (6 &mu;g/mL) hepatocytes exhibited increased levels of NF-&kappa;B (p65 and I&kappa;B&alpha;) and MAPK (p38, ERK, JNK) phosphorylation as well as increased binding activity of p65 to target pro-inflammatory gene promoters, and these effects were suppressed by pretreatment with 50 &mu;M EGCG. Moreover, the reduction in Nrf2 signaling and antioxidant enzyme activities induced by LPS stimulation were reversed upon EGCG treatment. In vivo experiments demonstrated the protective role of EGCG in response to GalN/LPS-induced mortality and oxidative damage. Together, our results suggest that EGCG is hepatoprotective via inhibition of MAPK/NF-&kappa;B signaling and activation of the Nrf2 cascade. This information might help design strategies for counteracting hepatitis in ruminants and monogastric animals

The Characteristics of Multilocus Sequence Typing, Virulence Genes and Drug Resistance of <i>Klebsiella pneumoniae</i> Isolated from Cattle in Northern Jiangsu, China

Klebsiella pneumoniae (K. pneumoniae) induced bovine mastitis has been becoming one of the dominantly pathogenic bacteria in cases of bovine mastitis, and is threatening public health through dairy products. In order to explore the characteristics of multilocus sequence typing (MLST), virulence gene carrying, and the relationship between virulence genes and the antibiotic resistance of Klebsiella pneumoniae from dairy cattle in northern Jiangsu, 208 dairy milk samples were collected from four dairy farms in northern Jiangsu. A total of 68 isolates were obtained through bacterial isolation, purification, and 16S rDNA identification. Eleven virulence genes were detected by specific PCR. The susceptibility of the isolates to antimicrobials was analyzed using the Kirby–Bauer method. The Pearson correlation coefficient was used to analyze the correlation between the presence of virulence genes and the phenotype of drug resistance. ST 2661 was the most prevalent type of K. pneumoniae (13/68, 19.1%) among the 23 ST types identified from the 68 isolates. The virulence gene allS was not detected, but the positive detection rates of the virulence genes fimH, ureA, uge and wabG were 100.0%. Notably, the detection rates of genes rmpA and wcaG, related to the capsular polysaccharide, were 4.4% and 11.8%, respectively, which were lower than those of genes related to siderophores (kfuBC, ybtA and iucB at 50.0%, 23.5%, and 52.9%, respectively). The K. pneumoniae isolates were sensitive to ciprofloxacin, nitrofurantoin, and meropenem. However, the resistance rate to penicillin was the highest (58/68, 85.3%), along with resistance to amoxicillin (16/68, 23.5%). The results revealed the distribution of 23 ST types of K. pneumoniae from the milk from bovine-mastitis-infected dairy cows in northern Jiangsu, and the expression or absence of the virulence gene kfuBC was related to the sensitivity to antibiotics. The current study provides important information relating to the distribution and characteristics of K. pneumoniae isolated from dairy cows with clinical bovine mastitis, and is indicative of strategies for improving the treatment of K. pneumoniae-induced bovine mastitis

Divergent roles of amino acid residues inside and outside the BB loop affect human Toll-like receptor (TLR)2/2, TLR2/1 and TLR2/6 responsiveness.

TLR2 specifically recognizes a wide range of ligands by homodimerizing or heterodimerizing with TLR1 or TLR6. However, the molecular basis of the specific signalling transduction induced by TLR2 homodimerization or heterodimerization with TLR1 or TLR6 is largely unknown. In this study, we found three amino acid residues, two (663L and 688N) outside and one (681P) inside the BB loop, which were conserved in all of the TLRs, except for the TLR3 toll/IL-1R(TIR) domain. The responsiveness of human TLR2/2, TLR2/1 or TLR2/6 was completely lost when 663L and 688N were replaced with the corresponding amino acid residues in the TLR3 TIR domain, respectively. However, the response of TLR2 (P681A) to the high concentration of TLR2/TLR6 agonist was almost intact, but the activity of TLR2 (P681A) was greatly reduced when stimulated with the TLR2/1 agonist or the TLR2/2 agonist. Although the surface expression of TLR2 (L663E) was sharply reduced, both the intracellular distribution and the surface expression of all of the other TLR2 mutants were unchanged. The ability of all three TLR2 mutants to recruit MyD88, was consistent with their responsivenesses. Computer modelling indicated that the surface negative charge of all of the TLR2 mutants' BB loops was reduced. Thus, our data demonstrated that the 663L and 688N residues outside of the BB loop were essential for the responsiveness of TLR2/2, TLR2/1 and TLR2/6, but the 681P residue inside of the BB loop exhibited divergent roles in TLR2/2, TLR2/1 and TLR2/6 signalling transduction, thereby providing clues regarding the specific signalling transduction of TLR2/2, TLR2/1 and TLR2/6

<i>Lycium barbarum</i> Polysaccharide Inhibits <i>E. coli</i>-Induced Inflammation and Oxidative Stress in Mammary Epithelial Cells of Dairy Cows via SOCS3 Activation and MAPK Suppression

Escherichia coli (E. coli) is one of the main causative agents of mastitis in dairy cows. Lycium barbarum polysaccharide (LBP) has a variety of physiological effects as it has antioxidants, it is hypoglycemic, it has anti-aging properties, it is neuroprotective, immune boosting, and it has anti-inflammatory effects in vivo and in vitro. In this study, we examined whether LBP affects the expression of pro-inflammatory factors, and the mitogen-activated protein kinase (MAPK) signaling pathway via activation of the suppressor of cytokine signaling-3 (SOCS3) in E. coli-induced primary bovine mammary epithelial cell (pbMEC) inflammatory responses. The experiment was designed with the control group (NC), cells were treated with E. coli for 6 h as the E. coli group (E. coli), and cells were pretreated with 100 μg/mL or 300 μg/mL of LBP for 24 h, followed by the addition of E. coli for 6 h as the E. coli + low level (E + LL) or E. coli + high level (E + HL) groups. The addition of LBP did not alter the cell viability of pbMEC in a dose-dependent assay. Pretreatment with LBP significantly decreased the expression of pro-inflammatory genes (IL1B, MAPK14, COX-2, iNOS) and proteins (COX-2, IL-1β, TNF-α) in the cells challenged by E. coli as compared with the control group (p E. coli stimulation significantly increased the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in pbMEC, and decreased the antioxidants’ capacity with regard to decreased superoxide dismutase (SOD) and total antioxidant capacity (T-AOC); however, pretreatment with LBP reversed the oxidative stress and inhibition of antioxidants in cells challenged by E. coli. Moreover, LBP reversed the upregulated expression of the components of the MAPK pathway (increased phosphorylation level of p38, JNK, and ERK), followed by E. coli stimulation. Consistently, cells exposed to E. coli strengthened the staining of p38, whereas pretreatment of LBP weakened the staining of p38 in cells challenged by E. coli. Notably, the expression of SOCS3 was increased by LBP added to the cells in a dose-dependent manner. Additionally, the level of decreased expression of proinflammatory factors (IL-1β, TNF-α, and COX-2) was higher in the E + LL group than in the E + HL group. These results indicate that LBP pretreatment is effective in the alleviation of E. coli-induced inflammatory and oxidative responses in pbMEC through activation of SOCS3 and depression of MAPK signaling. As such, this might help us to develop molecular strategies for mitigating the detrimental effects of clinical bovine mastitis

Large-Scale and Flexible Self-Powered Triboelectric Tactile Sensing Array for Sensitive Robot Skin

Advances in flexible and multifunctional electronic devices have enabled the realization of sophisticated skin for robotics applications. In this paper, a large-scale, flexible and self-powered tactile sensing array (TSA) for sensitive robot skin is demonstrated based on the triboelectric effect. The device, with 4 × 4 sensing units, was composed of a top triboelectric polyethylene terephthalate (PET) layer, a bottom triboelectric copper (Cu) layer and a bottom PET substrate. A low-cost roll-to-roll ultraviolet embossing fabrication process was induced to pattern the large-scale top PET film with microstructures for high-output performance. The working mechanism and output performance of the triboelectric TSA were demonstrated and characterized, exhibiting good stability and high sensitivity. By integrating a tactile feedback system, the large-scale TSA, acting as intelligent skin for an industrial robot, was able to realize emergency avoidance and safety stop for various unknown obstacles under various working conditions. The system also has good real-time performance. By using a large-scale roll-to-roll fabrication method, this work pushes forward a significant step to self-powered triboelectric TSA and its potential applications in intelligent robot skin

A two-step carbon fiber surface treatment and its effect on the interfacial properties of CF/EP composites: The electrochemical oxidation followed by grafting of silane coupling agent

A two-step carbon fiber surface treatment and its effect on the interfacial properties of CF/EP composites: The electrochemical oxidation followed by grafting of silane coupling agen

Genome-Wide Association Study on Reproduction-Related Body-Shape Traits of Chinese Holstein Cows

Reproduction is an important production activity for dairy cows, and their reproductive performance can directly affect the level of farmers’ income. To better understand the genomic regions and biological pathways of reproduction-related traits of dairy cows, in the present study, three body shape traits—Loin Strength (LS), Rump Angle (RA), and Pin Width (PW)—were selected as indicators of the reproductive ability of cows, and we conducted genome-wide association analyses on them. The heritability of these three traits was medium, ranging from 0.20 to 0.38. A total of 11 significant single-nucleotide polymorphisms (SNPs) were detected associated with these three traits. Bioinformatics analysis was performed on genes close to the significant SNPs (within 200 Kb) of LS, RA, and PW, and we found that these genes were totally enriched in 20 gene ontology terms and six KEGG signaling pathways. Finally, the five genes CDH12, TARP, PCDH9, DTHD1, and ARAP2 were selected as candidate genes that might affect LS. The six genes LOC781835, FSTL4, ATG4C, SH3BP4, DMP1, and DSPP were selected as candidate genes that might affect RA. The five genes USP6NL, CNTN3, LOC101907665, UPF2, and ECHDC3 were selected as candidate genes that might affect the PW of Chinese Holstein cows. Our results could provide useful biological information for the improvement of body shape traits and contribute to the genomic selection of Chinese Holstein cows