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The enterohepatic Helicobacter species Helicobacter hepaticus colonizes the murine intestinal and hepatobiliary tract and is associated with chronic intestinal inflammation, gall stone formation, hepatitis, and hepatocellular carcinoma. Thus far, the role of H. hepaticus motility and flagella in intestinal colonization is unknown. In other, closely related bacteria, late flagellar genes are mainly regulated by the sigma factor FliA (σ28). We investigated the function of the H. hepaticus FliA in gene regulation, flagellar biosynthesis, motility, and murine colonization. Competitive microarray analysis of the wild type versus an isogenic fliA mutant revealed that 11 genes were significantly more highly expressed in wild-type bacteria and 2 genes were significantly more highly expressed in the fliA mutant. Most of these were flagellar genes, but four novel FliA-regulated genes of unknown function were identified. H. hepaticus possesses two identical copies of the gene encoding the FliA-dependent major flagellin subunit FlaA (open reading frames HH1364 and HH1653). We characterized the phenotypes of mutants in which fliA or one or both copies of the flaA gene were knocked out. flaA_1 flaA_2 double mutants and fliA mutants did not synthesize detectable amounts of FlaA and possessed severely truncated flagella. Also, both mutants were nonmotile and unable to colonize mice. Mutants with either flaA gene knocked out produced flagella morphologically similar to those of wild-type bacteria and expressed FlaA and FlaB. flaA_1 mutants which had flagella but displayed reduced motility did not colonize mice, indicating that motility is required for intestinal colonization by H. hepaticus and that the presence of flagella alone is not sufficient.  相似文献   
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Spinal muscular atrophy (SMA) is a genetic neurodegenerative disorder leading to immobilization and premature death. Currently, three alternative therapeutic options are available. Therefore, biomarkers that might reflect or predict the clinical course of the individual patient with treatment are of great potential use. Currently, the antisense oligonucleotide nusinersen is the prevalent and longest validated therapy for SMA. We analysed CSF candidate biomarkers for degenerative CNS processes (namely phosphorylated heavy chain (pNf-H), light-chain neurofilaments (NfL), total tau protein (T-Tau), neurogranin, β-secretase BACE-1 and alpha-synuclein) in 193 CSF samples of 44 paediatric SMA types 1, 2 and 3 patients before and under nusinersen treatment and related them to standardized clinical outcome scores in a single-centre pilot study. pNf-H and NfL correlated with disease severity and activity, emphasizing their relevance as marker of neuronal loss and clinical outcome. T-Tau was significantly correlated with motor function scores in SMA type 1 making it an interesting marker for treatment response. Additionally, baseline T-Tau levels were elevated in most SMA patients possibly reflecting the extension of neuronal degeneration in paediatric-onset SMA. Further investigations of these CSF proteins might be beneficial for paediatric SMA subtypes and treatment modalities as an indicator for clinical outcome and should be analysed in larger cohorts.  相似文献   
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It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus striatum (CS) after 6-hydroxydopamine injection in the substantia nigra. To study the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) in this experimental paradigm, we have examined its activity by assessing the accumulation of l-3,4-dihydroxyphenylalanine after inhibiting the subsequent enzyme in the DA synthetic pathway, aromatic l-amino acid decarboxylase, with 3-hydroxybenzylhydrazine. In addition the amount of TH protein was assessed by western blotting and its distribution in the CS was examined using immunohistochemical methods. 6-hydroxydopamine injection produced a significant decrease in DA levels and l-3,4-dihydroxyphenylalanine accumulation, as well as decreases in TH protein and TH immunoreactive fibres in the CS. After nicotine treatment, the decrease in TH protein in the CS was significantly reduced, with a concomitant preservation of TH activity, but nicotine did not alter the number of TH immunoreactive fibres. The activity and amount of TH did not change in the contralateral (intact) CS. Thus, nicotine induces long lasting TH plasticity in the degenerating CS. A synergistic action of nicotine-activated and lesion-originated signals appears necessary for the expression of this neuronal molecular plasticity.  相似文献   
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Results of previous work suggest a preference of adult observers for cute compared to less cute infants. In Study 1 we investigated whether the preference for cute infants depends on the ethnicity and species of the infant. We simultaneously presented two faces (one cute and one less cute) and asked Caucasian participants to choose the infant to whom they would rather give a toy (Task 1) and which infant they would rather adopt (Task 2). The infants were Caucasian or African human babies or dog puppies. For all face categories and in both tasks we found a strong preference for cute infants. A possible reason for preferring cute infants may be that cute infants look healthier than less cute infants. To investigate whether cuteness is associated with the assessment of health we conducted Study 2. Faces of Caucasian and African infants and dog puppies were rated for cuteness and health. The findings revealed a significant relationship between health and cuteness evaluation across all stimuli. We suggest that one reason why cute infants are preferred might be because they are perceived as being healthier.  相似文献   
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Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus subsp. gallolyticus), a member of group D streptococci, is an inhabitant of the animal and human gastrointestinal tract. Furthermore, it is a facultative pathogen which causes e.g. endocarditis, septicemia and mastitis. S. gallolyticus subsp. gallolyticus may be transmitted either directly or indirectly between animals and humans. However, the transmission routes are an unsolved issue. In this study, we present systematic analyses of an S. gallolyticus subsp. gallolyticus isolate of an infective endocarditis patient in relation to isolates of his laying hen flock. Isolates from pooled droppings of laying hens, pooled dust samples and human blood culture were characterized by using multilocus sequence typing (MLST) and DNA fingerprinting. MLST revealed the same allelic profile of isolates from the human blood culture and from the droppings of laying hens. In addition, these isolates showed clonal identity regarding a similar DNA fingerprinting pattern. For the first time, we received a hint that transmission of S. gallolyticus subsp. gallolyticus between poultry and humans may occur. This raises the question about the zoonotic potential of isolates from poultry and should be considered in future studies.  相似文献   
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