643 research outputs found

    Fatty acid composition of sprat (Sprattus sprattus) and herring (Clupea harengus) in the Baltic Sea as potential prey for salmon (Salmo salar)

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    Sprat (Sprattus sprattus) and small herring (Clupea harengus) are the dominant prey fish of Atlantic salmon (Salmo salar) in the Baltic Sea. If the fatty acid (FA) proportions of sprat and herring differ, the dietary history of ascending salmon could be determined from their FA profiles. Therefore, we investigated the FA composition of several age groups of whole sprat and small herring, caught from the three main feeding areas of salmon in autumn and spring. Oleic acid (18: 1n-9) was the most prevalent FA in sprat and characteristic of this species. In herring, palmitic acid (16: 0) was the most common FA, but herring lipid was characterized by n-6 polyunsaturated FAs, and moreover, by palmitoleic acid (16: 1n-7) and vaccenic acid (18: 1n-7). Due to the higher lipid content of sprat, the concentrations of all other FAs, excluding these, were higher in sprat than in herring. The concentration of docosahexaenoic acid (DHA, 22: 6n-3) increased with an increase in the lipid content and was consequently highest in the youngest specimens, being in young sprat almost double that of young herring, and 2.6 times higher in the sprat biomass than in that of herring. As a result of a decrease in the DHA concentration with age, the ratio thiamine/DHA increased with respect to age in both species, and was lower in sprat than in herring. It is concluded that an abundance of DHA in the diet of salmon most likely increases oxidative stress because of the susceptibility of DHA to peroxidation, and thus decreases thiamine resources of fasting, prespawning salmon. Because the FA composition of sprat and herring differs, and the relative abundancies of prey fish differ between the feeding areas of salmon, the feeding area of ascending salmon can most probably be derived by comparing their FA profiles.Peer reviewe

    Intrapopulation genotypic variation in leaf litter chemistry does not control microbial abundance and litter mass loss in silver birch, Betula pendula

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    Background and aims Differences among plant genotypes can influence ecosystem functioning such as the rate of litter decomposition. Little is known, however, of the strength of genotypic links between litter quality, microbial abundance and litter decomposition within plant populations, or the likelihood that these processes are driven by natural selection. Methods We used 19 Betula pendula genotypes randomly selected from a local population in south-eastern Finland to establish a long-term, 35-month litter decomposition trial on forest ground. We analysed the effect of litter quality (N, phenolics and triterpenoids) of senescent leaves and decomposed litter on microbial abundance and litter mass loss. Results We found that while litter quality and mass loss both had significant genotypic variation, the genotypic variation among silver birch trees in the quantity of bacterial and fungal DNA was marginal. In addition, although the quantity of bacterial DNA at individual tree level was negatively associated with most secondary metabolites of litter and positively with litter N, litter chemistry was not genotypically linked to litter mass loss. Conclusions Contrary to our expectations, these results suggest that natural selection may have limited influence on overall microbial DNA and litter decomposition rate in B. pendula populations by reworking the genetically controlled foliage chemistry of these populations.Peer reviewe

    Inverse electron demand Diels-Alder click chemistry for pretargeted PET imaging and radioimmunotherapy

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    This approach leverages the rapid, bio-orthogonal inverse electron demand Diels-Alder reaction between a radiolabeled tetrazine and a trans-cyclooctene-bearing antibody to enable pretargeted positron emission tomography imaging and endoradiotherapy in a murine model of cancer. Radiolabeled antibodies have shown promise as tools for both the nuclear imaging and endoradiotherapy of cancer, but the protracted circulation time of radioimmunoconjugates can lead to high radiation doses to healthy tissues. To circumvent this issue, we have developed an approach to positron emission tomography (PET) imaging and radioimmunotherapy (RIT) predicated on radiolabeling the antibody after it has reached its target within the body. This in vivo pretargeting strategy is based on the rapid and bio-orthogonal inverse electron demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). Pretargeted PET imaging and RIT using TCO-modified antibodies in conjunction with Tz-bearing radioligands produce high activity concentrations in target tissues as well as reduced radiation doses to healthy organs compared to directly labeled radioimmunoconjugates. Herein, we describe how to prepare a TCO-modified antibody (humanized A33-TCO) as well as how to synthesize two Tz-bearing radioligands: one labeled with the positron-emitting radiometal copper-64 ([Cu-64]Cu-SarAr-Tz) and one labeled with the beta-emitting radiolanthanide lutetium-177 ([Lu-177]Lu-DOTA-PEG(7)-Tz). We also provide a detailed description of pretargeted PET and pretargeted RIT experiments in a murine model of human colorectal carcinoma. Proper training in both radiation safety and the handling of laboratory mice is required for the successful execution of this protocol.Peer reviewe

    Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life

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    Background Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. Methods At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965–1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. Results In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500–3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all). Conclusions In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower, birth weight in males may contribute to less favourable cardiovascular autonomic regulation and potentially to an elevated cardiovascular risk in later life

    Real-time monitoring of human blood-brain barrier disruption

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    Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography ( DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 mu V followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for bloodbrain barrier disruption augmented drug delivery.Peer reviewe

    DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

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    Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

    Does Future Diabetes Risk Impair Current Quality of Life? A Cross-Sectional Study of Health-Related Quality of Life in Relation to the Finnish Diabetes Risk Score (FINDRISC)

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    Objectives Present study examines the relationship between the estimated risk of developing type 2 diabetes (T2D) and health-related quality of life (HRQoL). We quantify the association between Finnish Diabetes Risk Score (FINDRISC) and HRQoL, and examine the potential use of FINDRISC as tool to evaluate HRQoL indirectly. Methods We conducted a cross-sectional study comprising 707 Finnish people without a diagnosis of T2D between the ages of 51 and 75 years. The risk of developing T2D was assessed using the validated and widely used FINDRISC (range 0-26 points), and quality of life was measured using two preference-based HRQoL instruments (15D and SF-6D) and one health profile instrument (SF-36). Effects of the individual FINDRISC items and demographic and clinical characteristics, such as co-morbidities, on HRQoL were studied using multivariable Tobit regression models. Results Low HRQoL was significantly and directly associated with the estimated risk of developing T2D. An approximate 4-5 point change in FINDRISC score was observed to be associated with clinically noticeable changes in the preference-based instrument HRQoL index scores. The association between HRQoL and the risk of developing T2D was also observed for most dimensions of HRQoL in all applied HRQoL instruments. Overall, old age, lack of physical activity, obesity, and history of high blood glucose were the FINDRISC factors most prominently associated with lower HRQoL. Conclusions The findings may help the health care professionals to substantiate the possible improvement in glucose metabolism and HRQoL potentially achieved by lifestyle changes, and better convince people at high risk of T2D to take action towards healthier lifestyle habits. FINDRISC may also provide an accurate proxy for HRQoL, and thus by estimating the risk of T2D with the FINDRISC, information about patients' HRQoL may also be obtained indirectly, when it is not feasible to use HRQoL instruments.Peer reviewe

    Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition

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    Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta- coefficient -0.29, p = 0.001) and hippocampal volume (beta- coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p <0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15,95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.Peer reviewe
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