Fanningkryger1798

Fusarium graminearum is the main causal species of Fusarium head blight (FHB) globally. Recent changes in the trichothecene (toxin) types in the North American FHB pathogens support the need for continued surveillance. In this study, 461 isolates were obtained from symptomatic spikes of wheat, spelt, barley, and rye crops during 2018 and 2019. These were all identified to species and toxin types using molecular-based approaches. An additional set of 77 F. graminearum isolates obtained from overwintering crop residues during Winter 2012 were molecularly identified to toxin types. A subset of 31 F. graminearum isolates (15 15ADON and 16 3ADON) were assessed for mycelial growth, macroconidia, perithecia, and ascospore production, and sensitivity to two triazole fungicides. Ninety percent of isolates obtained from symptomatic spikes (n = 418) belonged to F. graminearum, with another four species found at a lower frequency (n = 39). F. graminearum isolates from symptomatic spikes were mainly of the 15ADON (95%), followed by 3ADON (4%), NIV (0.7%), and NX-2 (0.3%) toxin types. All F. graminearum isolates obtained from overwintering residue were of the 15ADON type. Toxin types could not be differentiated based on multivariate analysis of growth and reproduction traits. All isolates were sensitive to tebuconazole and metconazole fungicides in vitro. This study confirms the dominance of F. graminearum and suggests ecological and environmental factors that lead to similar composition of toxin types in Northern U.S. Our results are useful to assess the sustainability of FHB management practices and provide a baseline for future FHB surveys.Purpose We extended our earlier study on normative growth curves for intelligibility development in typical children from 30 to 119 months of age. We also determined quantile-specific age of steepest growth and growth rates. A key goal was to establish age-specific benchmarks for single-word and multiword intelligibility. Method This cross-sectional study involved collection of in-person speech samples from 538 typically developing children (282 girls and 256 boys) who passed speech, language, and hearing screening measures. One thousand seventy-six normal-hearing naïve adult listeners (280 men and 796 women) orthographically transcribed children's speech. Speech intelligibility was measured as the percentage of words transcribed correctly by naive adults, with single-word and multiword intelligibility outcomes modeled separately. Results The age range for 50% single-word intelligibility was 31-47 months (50th-5th percentiles), the age range for 75% single-word intelligibility was 49-87 months, and the age range for 90% intelligibility for single words was 83-120+ months. The same milestones were attained for multiword intelligibility at 34-46, 46-61, and 62-87 months, respectively. The age of steepest growth for the 50th percentile was 30-31 months for both single-word and multiword intelligibility and was later for children in lower percentiles. The maximum growth rate was 1.7 intelligibility percentage points per month for single words and 2.5 intelligibility percentage points per month for multiword intelligibility. Conclusions There was considerable variability in intelligibility development among typical children. For children in median and lower percentiles, intelligibility growth continues through 9 years. Children should be at least 50% intelligible by 48 months. Supplemental Material https//doi.org/10.23641/asha.16583426.During its progression from the nasopharynx to other sterile and non-sterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesised that the temperature adaptation is an important facet of pneumococcal survival in the host. Here, we evaluated the effect of temperature on pneumococcus and studied the role of glutamate dehydrogenase (GdhA) in thermal adaptation associated with virulence and survival. Microarray analysis revealed a significant transcriptional response to changes in temperature, affecting the expression of 252 genes in total at 34°C and 40°C relative to at 37°C. One of the differentially regulated genes was gdhA, which is upregulated at 40°C and downregulated at 34°C relative to 37°C. Deletion of gdhA attenuated the growth, cell size, biofilm formation, pH survival, and biosynthesis of proteins associated with virulence in a temperature-dependent manner. Moreover, deletion of gdhA stimulated formate production irrespective of temperature fluctuation. Finally, ΔgdhA grown at 40°C was less virulent compare to other temperatures or than the wild type at the same temperature in a Galleria mellonella infection model, suggesting that GdhA is required for pneumococcal virulence at elevated temperature.Coxiella burnetii, the causative agent of Query (Q) fever in humans, is an obligate intracellular bacterium. C. burnetii can naturally infect a broad range of host organisms (e.g., mammals and arthropods) and cell types. This amphotropic nature of C. burnetii, in combination with its ability to utilize both glycolytic and gluconeogenic carbon sources, suggests that the pathogen relies on metabolic plasticity to replicate in nutritionally diverse intracellular environments. To test the significance of metabolic plasticity in C. burnetii host cell colonization, C. burnetii intracellular replication in seven distinct cell lines was compared between a metabolically competent parental strain and a mutant, CbΔpckA, unable to undergo gluconeogenesis. Both the parental strain and CbΔpckA exhibited host cell-dependent infection phenotypes, which were influenced by alterations to host glycolytic or gluconeogenic substrate availability. Because the nutritional environment directly impacts host cell physiology, our analysis was extended to investigate the response of C. burnetii replication in mammalian host cells cultivated in a novel physiological medium based on the nutrient composition of mammalian interstitial fluid, Interstitial Fluid-modeled Medium (IFmM). An infection model based on IFmM resulted in exacerbation of a replication defect exhibited by CbΔpckA in specific cell lines. CbΔpckA was also attenuated during infection of an animal host. Overall, the study underscores that gluconeogenic capacity aids C. burnetii amphotropism and that the amphotropic nature of C. burnetii should be considered when resolving virulence mechanisms in this pathogen.Human cystic echinococcosis, caused by the larval stage of echinococcus granulus sensu lato, has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce lesion microenvironment, however cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironment are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, peri-lesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations, and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between peri-lesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of innate lymphocyte 2 and plasmacytoid dendritic cells were higher in peri-lesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was up-regulated in these cells. Seven subsets of CD4+ T cell populations were found, and there were more Treg-CD4+ T and Th2-CD4+ T cells in peri-lesion tissue than those in adjacent normal tissue. There was close contact between CD4+ T cells and ILC2 and pDCs cells, which caused up-regulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in peri-lesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the CE lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironment at single-cell level, and provides potential target signatures for diagnosis and immunotherapies.Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, is an enzootic, obligate intracellular bacterial pathogen. Nitric oxide (NO) synthesized by the inducible nitric oxide synthase (iNOS) is a potent antimicrobial component of innate immunity and has been implicated in the control of virulent Rickettsia spp. in diverse cell types. In this study, we examined the antibacterial role of NO on R. rickettsii. Our results indicate that NO challenge dramatically reduces R. rickettsii adhesion through the disruption of bacterial energetics. Additionally, NO-treated R. ALK cancer rickettsii were unable to synthesize protein or replicate in permissive cells. Activated, NO-producing macrophages restricted R. rickettsii infections, but inhibition of iNOS ablated the inhibition of bacterial growth. These data indicate that NO is a potent anti-rickettsial effector of innate immunity that targets energy generation in these pathogenic bacteria to prevent growth and subversion of infected host cells.Periodontal disease is considered to arise from an imbalance in the interplay between the host and its commensal microbiota, characterized by inflammation, destructive periodontal bone loss and a dysbiotic oral microbial community. The neutrophil is a key component of defence of the periodontium defects in their number or efficacy of function predisposes individuals to development of periodontal disease. Paradoxically, neutrophil activity, as part of a deregulated inflammatory response, is considered to be an important element in the destructive disease process. In this investigation we examined the role the neutrophil plays in the regulation of the oral microbiota, by analysis of the microbiome composition in mice lacking the CXCR2 neutrophil receptor required for recruitment to the periodontal tissues. A breeding protocol was employed which ensured that only the oral microbiota of wild type (CXCR2+/+) mice was transferred to subsequent generations of wild type, heterozygote and homozygote littermates. In the absence of neutrophils, the microbiome undergoes a significant shift in total load and composition compared to when normal levels of neutrophil recruitment into the gingival tissues occur, and this is accompanied by a significant increase in periodontal bone pathology. However, transfer of the oral microbiome of CXCR2-/- mice into germ free CXCR2+/+ mice led to restoration of the microbiome to the wild type CXCR2+/+ composition and the absence of pathology. These data demonstrate that the composition of the oral microbiome is inherently flexible and is governed to a significant extent by the genetics and resultant phenotype of the host organism.Streptococcus agalactiae (Group B Streptococcus, GBS), is an opportunistic pathogen capable of causing invasive disease in susceptible individuals including the newborn. Currently GBS is the leading cause of meningitis in the neonatal period. We have recently shown that GBS interacts directly with host type III intermediate filament vimentin to gain access to the central nervous system. This results in characteristic meningeal inflammation and disease progression; however, the specific role of vimentin in the inflammatory process is unknown. Here we investigate the contribution of vimentin to the pathogenesis of GBS meningitis. We show that a CRISPR targeted deletion of vimentin in human cerebral microvascular endothelial cells (hCMEC) reduced GBS induction of neutrophil attractants IL-8 and CXCL-1, as well as NFκB activation. We further show that inhibition of vimentin localization also prevented similar chemokine activation by GBS. One known chemokine regulator is the nucleotide-binding oligomerization domain containing protein 2 (NOD2), which is known to interact directly with vimentin.