Fanningbech2388

Obesity is an established risk factor for breast cancer in post-menopausal women, being associated with elevated serum levels of leptin. Although overweight is a common condition in cat, the role of leptin and its receptor in feline mammary carcinoma remains unsettled. In this study, serum leptin and leptin receptor (ObR) levels were investigated in 58 cats with mammary carcinoma and compared with those of healthy animals, as were the expression levels of leptin and ObR in tumor tissues. The results showed that the Free Leptin Index is significantly decreased in cats with mammary carcinoma (p = 0.0006), particularly in those with luminal B and HER2-positive tumors, and that these animals also present significantly lower serum leptin levels (p less then 0.0001 and p less then 0.005, respectively). Interestingly, ulcerating tumors (p = 0.0005) and shorter disease-free survival (p = 0.0217) were associated to serum leptin levels above 4.17 pg/mL. In contrast, elevated serum ObR levels were found in all cats with mammary carcinoma (p less then 0.0001), with levels above 16.89 ng/mL being associated with smaller tumors (p = 0.0118), estrogen receptor negative status (p = 0.0291) and increased serum levels of CTLA-4 (p = 0.0056), TNF-α (p = 0.0025), PD-1 (p = 0.0023), and PD-L1 (p = 0.0002). In tumor samples, leptin is overexpressed in luminal B and triple-negative carcinomas (p = 0.0046), whereas ObR is found to be overexpressed in luminal B tumors (p = 0.0425). Altogether, our results support the hypothesis that serum levels of leptin and ObR can be used as biomarkers of specific feline mammary carcinoma subtypes, and suggests the use of leptin antagonists as a therapeutic tool, reinforcing the utility of the cat as a cancer model.Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Inhalation of contaminated dust particles or aerosols originating from animals (esp. small ruminants) is the main source of human infection. Hence, an active early warning system for Q fever in German small ruminant livestock was conceptualized to prevent human infections. First, we describe the best practice for establishing this system before evaluating its feasibility, as the combination of both evokes conflicts. Vaginal swabs from all husbandry systems with a focus on reproductive females should pooled and investigated by PCR to detect C. TMP195 burnetii-shedding animals. Multistage risk-based sampling shall be carried out at the flock level and within-flock level. At the flock level, all flocks that are at risk to transmit the pathogen to the public must be sampled. At the within-flock level, all primi- and multiparous females after lambing must be tested in order to increase the probability of identifying a positive herd. Sampling should be performed during the main lambing period and before migration in residential areas. Furthermore, individual animals should be tested before migration or exhibition to ensure a negative status. If a flock tests positive in at least one individual sample, then flock-specific preventive measures should be implemented. This approach implies huge financial costs (sample testing, action/control measures). Hence, taking the step to develop more feasible and affordable preventive measures, e.g., vaccinating small ruminant flocks, should replace testing wherever justifiable.Mastitis remains a major infection of dairy cows and an important issue for the dairy farmers, and Escherichia coli (E. coli) bovine mastitis is a disease of significant economic importance in the dairy industry. Our study identified six isolates belong to phylogroup B2 from 69 bovine mastitis E. coli strains. Except for one serotype O1 strain, all group B2 isolates were identified into serotype O2 and showed significantly higher mortality in the mouse infection than other phylogroups' strains. Genomic analyses and further tests were performed to examine the role of secretion systems, fimbriae, and toxins during the systemic infection of O2K1 strain BCE049. Two integral T6SS loci and three predicted effectors clusters were found to assemble the functional T6SS complex and deliver diverse toxic effectors to modulate bacterial virulence in the mouse infection model. A total of four T4SS loci were harbored in the BCE049 genome, three of them are encoded in different plasmids, respectively, whereas the last one locates within the bacterial chromosome at FQU84_16715 to FQU84_16760, and was significantly involved in the bacterial pathogenicity. Numerous predicted pilus biosynthesis gene loci were found in the BCE049 genome, whereas most of them lost long fragments encoding key genes for the pili assembly. Unexpectedly, a type IV pilus gene locus locating at FQU84_01405 to FQU84_01335 in the plasmid 2, was found to be required for the full virulence of mastitis strain BCE049. It should be noted that a genetic neighborhood inserted with diverse genes is encoded by the plasmid 1, which harbors three prominent toxins including β-hemolysin, cytotoxic necrotizing factor 2 and cytolethal distending toxin type III. Consequent studies verified that these toxins significantly contributed to the bacterial pathogenicity. These findings provide a molecular blueprint for understanding the underlying mechanisms employed by the bovine mastitis E. coli to colonize in host and cause systemic infection.Pasteurella multocida is a gram-negative opportunistic pathogen that causes various diseases in poultry, livestock, and humans, resulting in huge economic losses. Pasteurella multocida serotype A CQ6 (PmCQ6) is a naturally occurring attenuated strain, while P. multocida serotype A strain CQ2 (PmCQ2) is a highly virulent strain isolated from calves. Compared with PmCQ2, it was found that bacterial loads and tissue lesions of lung tissue significantly decreased and survival rates significantly improved in mice infected with PmCQ6 by intranasal infection. However, comparative genome analysis showed that the similarity between the two strains is more than 99%. To further explore the virulence difference mechanism of PmCQ2 and PmCQ6, transcriptome sequencing analysis of the two strains was performed. The RNA sequencing analysis of PmCQ2 and PmCQ6 showed a large number of virulence-related differentially expressed genes (DEGs) in vivo and in vitro. Among them, 38 virulence-related DGEs were significantly up-regulated due to PmCQ6 infection, while the number of PmCQ2 infection was 46, much more than PmCQ6.