| 1. |
- Björkgren, Ida, et al.
(författare)
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Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane.
- 2015
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 29:2, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- During epididymal sperm maturation, the lipid content of the sperm membrane is modified, which facilitates sperm motility and fertility. However, little is known about the mechanisms regulating the maturation process. By generating a conditional knockout (cKO) of Dicer1 in the proximal part of the mouse epididymis, we studied the role of RNA interference in epididymal functions. The Dicer1 cKO epididymis displayed an altered lipid homeostasis associated with a 0.6-fold reduction in the expression of the gene elongation of very long chain fatty acids-like 2, an enzyme needed for production of long-chain polyunsaturated fatty acids (PUFAs). Furthermore, the expression of several factors involved in cholesterol synthesis was up-regulated. Accordingly, the Dicer1 cKO sperm membrane showed a 0.7-fold decrease in long-chain PUFAs, whereas the amount of cholesterol in acrosome-reacted sperm displayed a 1.7-fold increase. The increased cholesterol:PUFA ratio of the sperm membrane caused breakage of the neck and acrosome region and immotility of sperm. Dicer1 cKO mice sperm also displayed reduced ability to bind to and fertilize the oocyte in vitro. This study thus shows that Dicer1 is critical for lipid synthesis in the epididymis, which directly affects sperm membrane integrity and male fertility.-Björkgren, I., Gylling, H., Turunen, H., Huhtaniemi, I., Strauss, L., Poutanen, M., Sipilä, P. Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane.
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| 2. |
- Hautala, Lauri, et al.
(författare)
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Probing RbBr solvation in freestanding sub-2 nm water clusters
- 2017
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 19:36, s. 25158-25167
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Tidskriftsartikel (refereegranskat)abstract
- Concentration dependent solvation of RbBr in freestanding sub-2 nm water clusters was studied using core level photoelectron spectroscopy with synchrotron radiation. Spectral features recorded from dilute to saturated clusters indicate that either solvent shared or contact ion pairs are present in increasing amount when the concentration exceeds 2 mol kg-1. For comparison, spectra from anhydrous RbBr clusters are also presented.
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| 3. |
- Le Joncour, Vadim, et al.
(författare)
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Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization.
- 2019
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- The current clinical care of glioblastomas leaves behind invasive, radio- and chemo-resistant cells. We recently identified mammary-derived growth inhibitor (MDGI/FABP3) as a biomarker for invasive gliomas. Here, we demonstrate a novel function for MDGI in the maintenance of lysosomal membrane integrity, thus rendering invasive glioma cells unexpectedly vulnerable to lysosomal membrane destabilization. MDGI silencing impaired trafficking of polyunsaturated fatty acids into cells resulting in significant alterations in the lipid composition of lysosomal membranes, and subsequent death of the patient-derived glioma cells via lysosomal membrane permeabilization (LMP). In a preclinical model, treatment of glioma-bearing mice with an antihistaminergic LMP-inducing drug efficiently eradicated invasive glioma cells and secondary tumours within the brain. This unexpected fragility of the aggressive infiltrating cells to LMP provides new opportunities for clinical interventions, such as re-positioning of an established antihistamine drug, to eradicate the inoperable, invasive, and chemo-resistant glioma cells from sustaining disease progression and recurrence.
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| 4. |
- Li, He, et al.
(författare)
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Stability and activity of Dictyoglomus thermophilum GH11 xylanase and its disulphide mutant at high pressure and temperature
- 2015
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Ingår i: Enzyme and microbial technology. - : Elsevier. - 0141-0229 .- 1879-0909. ; 70, s. 66-71
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Tidskriftsartikel (refereegranskat)abstract
- The functional properties of extremophilic Dictyoglomus thermophilum xylanase (XYNB) and the N-terminal disulphide-bridge mutant (XYNB-DS) were studied at high pressure and temperature. The enzymes were quite stable even at the pressure of 500 MPa at 80 °C. The half-life of inactivation in these conditions was over 30 h. The inactivation at 80 °C in atmospheric pressure was only 3-times slower. The increase of pressure up to 500 MPa at 80 °C decreased only slightly the enzyme's stability, whereas in 500 MPa the increase of temperature from 22 to 80 °C decreased significantly more the enzyme's stability. While the high temperature (80–100 °C) decreased the enzyme reaction with short xylooligosaccharides (xylotetraose and xylotriose), the high pressure (100–300 MPa) had an opposite effect. The temperature of 100 °C strongly increased the Km but did not affect the kcat to the same extent, thus indicating that the interaction of the substrate with the active site suffers before the catalytic reaction begins to decrease as the temperature rises. Circular dichroism spectroscopy showed the high structural stability of XYNB and XYNB-DS at 93 °C.
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| 5. |
- Li, He, et al.
(författare)
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Thermostabilization of extremophilic Dictyoglomus thermophilum GH11 xylanase by an N-terminal disulfide bridge and the effect of ionic liquid [emim] OAc on the enzymatic performance
- 2013
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Ingår i: Enzyme and microbial technology. - : Elsevier. - 0141-0229 .- 1879-0909. ; 53:6-7, s. 414-419
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, an extremophilic GH11 xylanase was stabilized by an engineered N-terminal disulphide bridge. The effect of the stabilization was then tested against high temperatures and in the presence of a biomass-dissolving ionic liquid, 1-ethyl-3-methylimidazolium acetate ([emim]OAc). The N-terminal disulfide bridge increased the half-life of a GH11 xylanase (XYNB) from the hyperthermophilic bacterium Dictyoglomus thermophilum by 10-fold at 100 °C. The apparent temperature optimum increased only by ∼5 °C, which is less than the corresponding increase in mesophilic (∼15 °C) and moderately thermophilic (∼10 °C) xylanases. The performance of the enzyme was increased significantly at 100–110 °C. The increasing concentration of [emim]OAc almost linearly increased the inactivation level of the enzyme activity and 25% [emim]OAc inactivated the enzyme almost fully. On the contrary, the apparent temperature optimum did not decrease to a similar extent, and the degree of denaturation of the enzyme was also much lower according to the residual activity assays. Also, 5% [emim]OAc largely counteracted the benefit obtained by the stabilizing disulfide bridge in the temperature-dependent activity assays, but not in the stability assays. Km was increased in the presence of [emim]OAc, indicating that [emim]OAc interfered the substrate–enzyme interactions. These results indicate that the effect of [emim]OAc is targeted more to the functioning of the enzyme than the basic stability of the hyperthermophilic GH11 xylanase.
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| 6. |
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| 7. |
- Tamminen, Inari S., et al.
(författare)
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Increased Heterogeneity of Bone Matrix Mineralization in Pediatric Patients Prone to Fractures: A Biopsy Study
- 2014
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 29:5, s. 1110-1117
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic osteoporosis (IOP) in children is characterized by fragility fractures and/or low bone mineral density in otherwise healthy individuals. The aim of the present work was to measure bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) in children with suspected IOP. Entire cross-sectional areas of transiliac bone biopsy samples from children (n=24, 17 boys; aged 6.7-16.6 years) with a history of fractures (n=14 with at least one vertebral fracture) were analyzed for cancellous (Cn) and cortical (Ct) BMDD. Outcomes were compared with normal reference BMDD data and correlated with the patients' clinical characteristics and bone histomorphometry findings. The subjects had similar average degree but significantly higher heterogeneity of mineralization in both Cn and Ct bone (Cn.CaWidth +23%, Ct.CaWidth +15%, p<0.001 and p=0.002, respectively), together with higher percentages of low mineralized cancellous (Cn.CaLow +35%, p<0.001) and highly mineralized cortical bone areas (Ct.CaHigh +82%, p=0.032). Ct.CaWidth and Ct.CaLow were positively correlated with mineralizing surface per bone surface (MS/BS; a primary histomorphometric determinant of bone formation) and with serum bone turnover markers (all p<0.05). The correlations of the mineralization heterogeneity with histomorphometric and serum bone turnover indices suggest that an enhanced variation in bone turnover/formation contributes to the increased heterogeneity of mineralization. However, it remains unclear whether the latter is cause for, or the response to the increased bone fragility in these children with suspected IOP. (c) 2014 American Society for Bone and Mineral Research.
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| 8. |
- Turunen, Heikki T, et al.
(författare)
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Members of the murine Pate family are predominantly expressed in the epididymis in a segment-specific fashion and regulated by androgens and other testicular factors.
- 2011
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Ingår i: Reproductive biology and endocrinology : RB&E. - : Springer Science and Business Media LLC. - 1477-7827. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Spermatozoa leaving the testis are not able to fertilize the egg in vivo. They must undergo further maturation in the epididymis. Proteins secreted to the epididymal lumen by the epithelial cells interact with the spermatozoa and enable these maturational changes, and are responsible for proper storage conditions before ejaculation. The present study was carried out in order to characterize the expression of a novel Pate (prostate and testis expression) gene family, coding for secreted cysteine-rich proteins, in the epididymis.
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| 9. |
- Turunen, Mikael J., et al.
(författare)
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Composition and microarchitecture of human trabecular bone change with age and differ between anatomical locations
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 54:1, s. 118-125
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Tidskriftsartikel (refereegranskat)abstract
- The microarchitecture of trabecular bone adapts to its mechanical loading environment according to Wolff's law and alters with age. Trabecular bone is a metabolically active tissue, thus, its molecular composition and microarchitecture may vary between anatomical locations as a result of the local mechanical loading environment. No comprehensive comparison of composition and microarchitecture of trabecular bone in different anatomical locations has been conducted. Therefore, the objective of this study was to compare the molecular composition and microarchitecture, evaluated with Fourier transform infrared (FTIR) microspectroscopy and micro-computed tomography (mu CT), respectively, in the femoral neck, greater trochanter and calcaneus of human cadavers. Specimens were harvested from 20 male human cadavers (aged 17-82 years) with no known metabolic bone diseases. Significant differences were found in composition and microarchitecture of trabecular bone between the anatomical locations. Compositional differences were primarily observed between the calcaneus and the proximal femur sites. Mineralization was higher in the greater trochanter than in the calcaneus (+2%, p<0.05) and crystallinity was lowest in the calcaneus (-24%, p<0.05 as compared to the femoral neck). Variation in the composition of trabecular bone within different parts of the proximal femur was only minor. Collagen maturity was significantly lower in greater trochanter than in femoral neck (-8%, p<0.01) and calcaneus (-5%, p<0.05). The greater trochanter possessed a less dense trabecular bone microarchitecture compared to femoral neck or calcaneus. Age related changes were mainly found in the greater trochanter. Significant correlations were found between the composition and microarchitecture of trabecular bone in the greater trochanter and calcaneus, indicating that both composition and microarchitecture alter similarly. This study provides new information about composition and microarchitecture of trabecular bone in different anatomical locations and their alterations with age with respect to the anatomical loading environments. (C) 2013 Elsevier Inc. All rights reserved.
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