| 1. |
- Kauppinen, Ari, et al.
(författare)
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Phage Biocontrol of Pseudomonas aeruginosa in Water
- 2021
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Bacteriophage control of harmful or pathogenic bacteria has aroused growing interest, largely due to the rise of antibiotic resistance. The objective of this study was to test phages as potential agents for the biocontrol of an opportunistic pathogen Pseudomonas aeruginosa in water. Two P. aeruginosa bacteriophages (vB_PaeM_V523 and vB_PaeM_V524) were isolated from wastewater and characterized physically and functionally. Genomic and morphological characterization showed that both were myoviruses within the Pbunavirus genus. Both had a similar latent period (50-55 min) and burst size (124-134 PFU/infected cell), whereas there was variation in the host range. In addition to these environmental phages, a commercial Pseudomonas phage, JG003 (DSM 19870), was also used in the biocontrol experiments. The biocontrol potential of the three phages in water was tested separately and together as a cocktail against two P. aeruginosa strains; PAO1 and the environmental strain 17V1507. With PAO1, all phages initially reduced the numbers of the bacterial host, with phage V523 being the most efficient (>2.4 log(10) reduction). For the environmental P. aeruginosa strain (17V1507), only the phage JG003 caused a reduction (1.2 log(10)) compared to the control. The cocktail of three phages showed a slightly higher decrease in the level of the hosts compared to the use of individual phages. Although no synergistic effect was observed in the host reduction with the use of the phage cocktail, the cocktail-treated hosts did not appear to acquire resistance as rapidly as hosts treated with a single phage. The results of this study provide a significant step in the development of bacteriophage preparations for the control of pathogens and harmful microbes in water environments.
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| 2. |
- Kämäläinen, Anna, et al.
(författare)
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GRN Variant rs5848 Reduces Plasma and Brain Levels of Granulin in Alzheimer's Disease Patients.
- 2013
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 33:1, s. 23-7
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants in the granulin (GRN) gene have been shown to increase the risk of Alzheimer's disease (AD). Here, we report that the A allele of rs5848 in GRN reduces plasma granulin levels in a dose-dependent manner in a clinically-defined AD sample cohort. Similarly, the mRNA levels of granulin were decreased with respect to A allele of rs5848 in the inferior temporal cortex of neuropathologically confirmed AD patients. Our findings suggest that the A allele of rs5848 is functionally relevant by reducing the expression of granulin.
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| 3. |
- Kärjä, Vesa, et al.
(författare)
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Does protein expression predict recurrence of benign World Health Organization grade I meningioma?
- 2010
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 41:2, s. 199-207
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the predictive value of recurrence of protein expression in surgical samples of meningiomas. Thus, the expression of proteins that have been reported to be associated with prognosis of meningiomas was assessed in a sample of 59 World Health Organization grade I tumors obtained after Simpson grade I to III surgical resection (complete excision) and that were followed for 6 to 16 years. The expression was investigated applying immunohistochemical and tissue microarray techniques. One protein, the hepatocytic growth factor receptor, of 22 investigated proteins, showed significantly differing expression when comparing the 38 nonrecurrent with the 21 recurrent World Health Organization grade I meningiomas. It is noteworthy however that by means of logistic regression analyses, the independent predictive value of this protein expression was not significantly associated with the recurrence. Furthermore, it is noteworthy that the proliferation rate estimated by means of Ki67 expression did not show a significant difference, being 3.3 +/- 0.4 for the nonrecurrent meningioma and 3.9 +/- 0.5 for the recurrent and ranging from 0% to 10%. A significant and differing Spearman rank order of correlation was noted between 19 pairs of the investigated proteins when comparing nonrecurrent with recurrent World Health Organization grade I meningiomas. None of these correlations, however, showed a significant association by means of logistic regression analyses. Our results indicate that the Simpson grade significantly alters the outcome of a World Health Organization I grade meningioma and a longer follow-up period significantly increases the risk of recurrence. The expression of none of the proteins or correlation between protein expressions previously reported to be of significance regarding recurrence can be recommended as a diagnostic tool while assessing the risk of recurrence of World Health Organization grade I meningiomas.
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| 4. |
- Laitera, Tiina, et al.
(författare)
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Increased gamma-Secretase Activity in Idiopathic Normal Pressure Hydrocephalus Patients with beta-Amyloid Pathology
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e93717-
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Tidskriftsartikel (refereegranskat)abstract
- The potential similarity between the brain pathology of idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer disease (AD) is intriguing and thus further studies focusing on the underlying molecular mechanisms may offer valuable information for differential diagnostics and the development of treatments for iNPH. Here, we investigated beta- and gamma-secretase activities in relation to amyloid-beta (A beta) pathology in the brain tissue samples collected from iNPH and AD patients. beta- and gamma-secretase activities were measured from the frontal cortical biopsies of 26 patients with suspected iNPH as well as post-mortem tissue samples from the inferior temporal cortex of 74 AD patients and eight subjects without neurofibrillary pathology. In iNPH samples with detectable A beta plaques, gamma-secretase activity was significantly increased (similar to 1.6-fold) when compared to iNPH samples without A beta plaques (p=0.009). In the AD samples, statistically significant differences in the gamma-secretase activity were not observed with respect to disease severity (mild, moderate and severe AD according to neurofibrillary pathology). Conversely, beta-secretase activity was unaltered in iNPH samples with or without A beta plaques, while it was significantly increased in relation to disease severity in the AD patients. These results show for the first time increased gamma-secretase but not b-secretase activity in the biopsy samples from the frontal cortex of iNPH patients with AD-like A beta pathology. Conversely, the opposite was observed in these secretase activities in AD patients with respect to neurofibrillary pathology. Despite the resemblances in the A beta pathology, iNPH and AD patients appear to have marked differences in the cellular mechanisms responsible for the production of A beta.
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| 5. |
- Natunen, Teemu, et al.
(författare)
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Effects of NR1H3 Genetic Variation on the Expression of Liver X Receptor alpha and the Progression of Alzheimer's Disease
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80700-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) has been postulated to involve defects in the clearance of amyloid-beta (A beta). Activation of liver X receptor alpha (LXR alpha) increases the expression of apolipoprotein E (ApoE) as well as cholesterol transporters ABCA1 and ABCG1, leading to augmented clearance of A beta. We have previously shown that the C allele of rs7120118 in the NR1H3 gene encoding LXR alpha reduces the risk of AD. Here, we wanted to assess whether the rs7120118 variation affects the progression of AD and modulates the expression of NR1H3 and its downstream targets APOE, ABCA1 and ABCG1. We utilized tissue samples from the inferior temporal cortex of 87 subjects, which were subdivided according to Braak staging into mild, moderate and severe AD groups on the basis of AD-related neurofibrillary pathology. APOE epsilon 4 allele increased soluble A beta 42 levels in the tissue samples in a dose-dependent manner, but did not affect the expression status of APOE. In contrast, the CC genotype of rs7120118 was underrepresented in the severe group, although this result did not reach statistical significance. Also, patients with the CC genotype of rs7120118 showed significantly decreased soluble A beta 42 levels as compared to the patients with TT genotype. Although the severity of AD did not affect NR1H3 expression, the mRNA levels of NR1H3 among the patients with CT genotype of rs7120118 were significantly increased as compared to the patients with TT genotype. These results suggest that genetic variation in NR1H3 modulates the expression of LXR alpha and the levels of soluble A beta 42.
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| 6. |
- Pikkarainen, Maria, et al.
(författare)
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Hyperphosphorylated tau in the occipital cortex in aged nondemented subjects
- 2009
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 68:6, s. 653-660
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Tidskriftsartikel (refereegranskat)abstract
- To determine the extent of neurodegeneration of the visual association cortex, we assessed hyperphosphorylated tau-immunoreactive (HPtau-IR) neurofibrillary tangles in Brodmann Areas 18/19 in nondemented and demented subjects. At least occasional HPtau-IR neurofibrillary tangles were seen in 24% of 59 nondemented subjects with ages at death ranging from 42 to 87 years. The incidence increased to 41% in the 32 nondemented subjects who had HPtau-IR pathology in the hippocampal region. Demented subjects with Braak Stages 0 to III and corticobasal degeneration, frontotemporal lobar degeneration with TAR DNA binding protein 43, vascular cognitive impairment, or dementia with Lewy bodies also had HPtau-IR pathology in Brodmann Areas 18/19. These results support the concept that the occipital association area may have enhanced vulnerability to neurodegeneration. Neuropathologic assessment of these areas is, therefore, recommended, particularly in subjects suspected or known to have had mild cognitive impairment. Occasional HPtau-IR lesions were also seen in the medial temporal gyrus. Thus, the question as to whether scattered HPtau-IR lesions in either temporal or occipital cortex indicate a neurodegenerative disease remains unresolved. Further systematic clinicopathologic studies are needed for an understanding of regional susceptibility to neurodegeneration and the significance of scattered HPtau-IR brain lesions.
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