Mitochondrial diseases are clinically and genetically heterogeneous disorders, caused by pathogenic variants in either the nuclear or mitochondrial genome. This heterogeneity is particularly striking for disease caused by variants in mitochondrial DNA-encoded tRNA (mt-tRNA) genes, posing challenges for both the treatment of patients and understanding the molecular pathology. In this review, we consider disease caused by the two most common pathogenic mt-tRNA variants m.3243A>G (within MT-TL1, encoding mt-tRNALeu(UUR) ) and m.8344A>G (within MT-TK, encoding mt-tRNALys ), which together account for the vast majority of all mt-tRNA-related disease. We compare and contrast the clinical disease they are associated with, as well as their molecular pathologies, and consider what is known about the likely molecular mechanisms of disease. Finally, we discuss the role of mitochondrial-nuclear crosstalk in the manifestation of mt-tRNA-associated disease and how research in this area not only has the potential to uncover molecular mechanisms responsible for the vast clinical heterogeneity associated with these variants but also pave the way to develop treatment options for these devastating diseases.Interferon regulatory factor 3 (IRF3) is a critical transcription factor for inducing production of type I interferons (IFN-I) and regulating host antiviral response. Although IRF3 activation during viral infection has been extensively studied, the inhibitory regulation of IRF3 remains largely unexplored. Here, we revealed that Midline-1 (MID1) is a ubiquitin E3 ligase of IRF3 that plays essential roles in regulating the production of IFN-I. We found that MID1 physically interacts with IRF3 and downregulates IRF3 protein levels. Next, we demonstrated that MID1 can induce K48-linked polyubiquitination of IRF3, thus lowing the protein stability of IRF3. Our further studies identified Lys313 as a major ubiquitin acceptor lysine of IRF3 induced by MID1. Finally, MID1-mediated ubiquitination and degradation of IRF3 restrict IFN-I production and cellular antiviral response. This study uncovers a role of MID1 in regulating innate antiviral immunity and may provide a potential target for enhancing host antiviral activity.
  Raw meat and meat products contaminated with Clostridioides difficile could be a vehicle for spreading community-associated C. difficile infection. This study was conducted to determine the occurrence of C. difficile in pork and poultry meat samples (n = 325) from retail establishments and in edible giblet samples (n = 36) from a poultry processing plant in Murcia (southeastern Spain). C. difficile was isolated after selective enrichment from 2% (6 of 361) of the samples, all of which were from the poultry processing plant. These isolates were recovered from 17% (6 of 36) of the edible chicken giblets, i.e., 28% (5 of 18) of the gizzard samples and 6% (1 of 18) of the liver samples. All six C. difficile isolates were negative for toxin A and B genes by PCR assay. These findings indicate that C. difficile can survive in the gastric acid of the chicken gizzard and could be transmitted to other meat products. However, the very low prevalence of C. difficile in the tested samples indicates that retail meat may not be an important source for transmission of C. difficile to humans.
 
  Salmonella is a foodborne pathogen commonly associated with poultry products. The aims of this work were to (i) estimate the impact of critical steps of the slaughter process on Salmonella detection from broiler chicken carcasses in two commercial poultry slaughter plants in Quebec, Canada; (ii) investigate the presence of Salmonella in the slaughter plant environment; (iii) describe, using a high-resolution melting (HRM) approach, the HRM Salmonella profiles and serotypes present on carcasses and in the slaughter plant environment; and (iv) evaluate whether the HRM flock status after chilling could be predicted by the flock status at previous steps of the slaughter process, the status of previous flocks, or the status of the processing environment, for the same HRM profile. Eight visits were conducted in each slaughter plant over a 6-month period. In total, 379 carcass rinsates from 79 flocks were collected at five critical steps of the slaughter process. Environmental samples were also collected from seven critical sites in each slaughter plant. The bleeding step was the most contaminated, with >92% positive carcasses. A decrease of the contamination along the slaughtering process was noted, with carcasses sampled after dry-air chilling showing ≤2.5% Salmonella prevalence. The most frequently isolated serotypes were Salmonella Heidelberg, Kentucky, and Schwarzengrund. The detection of the Salmonella Heidelberg 1-1-1 HRM profile on carcasses after chilling was significantly associated with its detection at previous steps of the slaughter process and in previously slaughtered flocks from other farms during a same sampling day. Results highlight the importance of the chilling step in the control of Salmonella on broiler chicken carcasses and the need to further describe and compare the competitive advantage of Salmonella serotypes to survive processing. The current study also illustrates the usefulness of HRM typing in investigating Salmonella contamination along the slaughter process.
 
  Toxoplasma gondii, a ubiquitous obligate intracellular parasite that can infect homeothermic animals, is one of the main pathogens causing foodborne diseases worldwide. In Gaza, Palestine, leafy vegetables are frequently eaten raw. The present study was carried out to investigate the occurrence of T. gondii oocyst in local leafy vegetables. Fifty samples each of six species of leafy plants sold in open-air markets, in supermarkets, and by retail sellers were randomly collected from March to August 2019, for a total of 300 samples. The samples were examined by light microscopy after flotation in Sheather's sucrose solution and by PCR assay of the pelleted samples. All suspect T. gondii oocysts were confirmed with a PCR assay.  https://www.selleckchem.com/products/cc-122.html  With the PCR assay of the pelleted samples, only 19 (6.33%) of the 300 samples were positive for T. gondii, whereas with the Sheather's flotation method, 35 (11.66%) of the 300 samples were positive. With the PCR assay, among the six plant types mint had the highest T. gondii prevalence (10.