76 research outputs found
Proteins associated with core biomarkers in early Alzheimer`s disease: A pilot study of levels in cerebrospinal fluid, serum or plasma
No full textBackground:The cerebrospinal fluid (CSF) biomarkers amyloid-beta 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) are considered to reflect core pathological features of Alzheimer’s disease (AD), and have consistently been reported to have high diagnostic accuracy for discriminating patients with AD from healthy elderly controls. Yet there are limitations to their use, and little is known about alternative proteins in CSF, as well as in blood. The failure of Aβ immunotherapy has forced AD research to examine additional factors, particularly in the early stages of disease. The APOE ε4 allele is the major genetic risk factor for sporadic AD, and data suggest that ApoE may alter Aβ clearance and/or metabolism during the disease process. Another apolipoprotein associated with Aβ metabolism is clusterin (ApoJ), suggested to prevent aggregation and also be involved in clearance of Aβ. Moreover, angiotensin-converting enzyme (ACE) is a protease known to mediate cleavage of Aβ in vitro, and there is some indication that the ACE gene may be a risk factor for AD, depending on the insertion/deletion (I/D) genotype. Neurofilament-light (NF-L), like tau, is a neuronal cytoskeletal protein. In this pilot study, levels of ApoE, clusterin, ACE and NF-L in CSF and/or blood have been investigated in patients with early AD and healthy elderly individuals, and comparisons made with ACE and APOE ε4-allele genotype.
Aims: To assess whether levels of these proteins altered significantly in early AD compared to levels in elderly control individuals healthy for their age, whether additional information could be obtained from comparisons with ACE and APOE polymorphisms, and to assess their potential diagnostic value as early-stage biomarkers for AD compared to Aβ and tau protein.
Methods: Commercial ELISA kits were used to analyze and compare the levels of Aβ42, Aβ40, T-tau, P-tau, ApoE, clusterin, ACE and NF-L in CSF and/or plasma or serum samples from 20 patients with early AD and 20 age-matched individuals healthy for their age. Real-time polymerase chain reaction was performed on genomic DNA purified from samples of whole-blood from all participants to determine the ACE I/D polymorphism. Comparison was also made regarding APOE ε4-allele status.
Results: Despite the low number of samples, a high diagnostic accuracy in the discrimination between patients with early AD and elderly control individuals was obtained with concentrations of Aβ42 and tau in CSF. No significant differences were found between patients with early AD and controls regarding levels of ApoE in serum, clusterin in CSF or plasma, or ACE in CSF or serum. There was no pathological relationship regarding ACE genotype and allele distribution. The APOE ε4-allele was associated with lower levels of serum ApoE, irrespective of diagnosis. CSF NF-L levels were significantly higher in patients compared to controls.
Conclusion: No disease-specific alterations were found in relation to ApoE, clusterin or ACE. Although NF-L in CSF showed a fairly good potential to distinguish the patients with early AD from elderly individuals healthy for their age, the diagnostic accuracy was below that of Aβ and tau protein, and it did not seem to provide improved discrimination as a biomarker. Thus, none of these proteins are likely candidates as biomarkers for early AD
Proteins associated with core biomarkers in early Alzheimer`s disease : A pilot study of levels in cerebrospinal fluid, serum or plasma
No full textBackground:The cerebrospinal fluid (CSF) biomarkers amyloid-beta 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) are considered to reflect core pathological features of Alzheimer’s disease (AD), and have consistently been reported to have high diagnostic accuracy for discriminating patients with AD from healthy elderly controls. Yet there are limitations to their use, and little is known about alternative proteins in CSF, as well as in blood. The failure of Aβ immunotherapy has forced AD research to examine additional factors, particularly in the early stages of disease. The APOE ε4 allele is the major genetic risk factor for sporadic AD, and data suggest that ApoE may alter Aβ clearance and/or metabolism during the disease process. Another apolipoprotein associated with Aβ metabolism is clusterin (ApoJ), suggested to prevent aggregation and also be involved in clearance of Aβ. Moreover, angiotensin-converting enzyme (ACE) is a protease known to mediate cleavage of Aβ in vitro, and there is some indication that the ACE gene may be a risk factor for AD, depending on the insertion/deletion (I/D) genotype. Neurofilament-light (NF-L), like tau, is a neuronal cytoskeletal protein. In this pilot study, levels of ApoE, clusterin, ACE and NF-L in CSF and/or blood have been investigated in patients with early AD and healthy elderly individuals, and comparisons made with ACE and APOE ε4-allele genotype. Aims: To assess whether levels of these proteins altered significantly in early AD compared to levels in elderly control individuals healthy for their age, whether additional information could be obtained from comparisons with ACE and APOE polymorphisms, and to assess their potential diagnostic value as early-stage biomarkers for AD compared to Aβ and tau protein. Methods: Commercial ELISA kits were used to analyze and compare the levels of Aβ42, Aβ40, T-tau, P-tau, ApoE, clusterin, ACE and NF-L in CSF and/or plasma or serum samples from 20 patients with early AD and 20 age-matched individuals healthy for their age. Real-time polymerase chain reaction was performed on genomic DNA purified from samples of whole-blood from all participants to determine the ACE I/D polymorphism. Comparison was also made regarding APOE ε4-allele status. Results: Despite the low number of samples, a high diagnostic accuracy in the discrimination between patients with early AD and elderly control individuals was obtained with concentrations of Aβ42 and tau in CSF. No significant differences were found between patients with early AD and controls regarding levels of ApoE in serum, clusterin in CSF or plasma, or ACE in CSF or serum. There was no pathological relationship regarding ACE genotype and allele distribution. The APOE ε4-allele was associated with lower levels of serum ApoE, irrespective of diagnosis. CSF NF-L levels were significantly higher in patients compared to controls. Conclusion: No disease-specific alterations were found in relation to ApoE, clusterin or ACE. Although NF-L in CSF showed a fairly good potential to distinguish the patients with early AD from elderly individuals healthy for their age, the diagnostic accuracy was below that of Aβ and tau protein, and it did not seem to provide improved discrimination as a biomarker. Thus, none of these proteins are likely candidates as biomarkers for early AD
STATE SELECTED PHOTODISSOCIATION IN BY ALL-OPTICAL TRIPLE RESONANCE SPECTROSCOPY
No full text[1] P. D. Kleiber, J. X. Wang, K. M. Sando, V. Zafiropulos and W. C. Stwalley, J. Chem. Phys., 95, 4168 (1991). [2] J. X. Wang. H. Wang, P. D. Kleiber, A. M. Lyyra and W. C. Stwalley, J. Phys. Chem. 95, 8040 (1991). [3] R. L. Dubs and P. S. Julienne, J. Chem. Phys. 95, 4177 (1991).Author Institution: University of Iowa; Physics Department, Temple UniversityFinal state analysis of the products of molecular photodissociation gives information about the dynamical evolution of the system from short to long range including information about nonadiabatic interaction between potential energy curves and the transition through different angular momentum coupling regions [1]. Applying the all-optical triple resonance (AOTR) technique, specific individual rovibrational levels in are selectively photodissociated [2]. Polarization of the resulting atomic fluorescence is measured and analyzed by multichannel quantum defect-half collision theory [3]
Gait Variability and Kinematic Alterations in People with Diabetes Mellitus and Peripheral Neuropathy
No full textBackground: People with diabetes and peripheral neuropathy have been reported to show alterations in lower limb joint function compared to healthy non-diabetic people. Specifically the maximum angular movement available at certain joints can be reduced during static, non-weight bearing tasks. Limited joint range of motion has the potential to compromise balance and stability thereby increasing the risk of falling. It is unclear whether a reduction in the extent of movement available at the joints is reflected by a reduction in the amount of angular movement actually utilised during a functional task such as stair negotiation. The aim of this study was to determine if people with diabetes show reduced dynamic range of motion at the ankle, knee and hip joints during stair ascent and descent in comparison to controls. Falls risk during stair negotiation was calculated by measuring the degree of variability in dynamic joint range of motion. Methods: Data were generated from three groups: subjects with diabetes and peripheral neuropathy (DPN), diabetes without peripheral neuropathy (DM), and healthy controls (Ctl). The study was conducted in a gait laboratory using motion capture and related 3D software for analysis. Joint range of motion for the ankle, knee, and hip were captured during level walking, stair ascent, and descent. A seven step, bespoke staircase was fabricated for this purpose. Analysis of Variance (ANOVA) and Newman-Keuls tests were used to analyse the data. Results: Significantly reduced ankle range of motion, in the sagittal plane, was observed in the DPN group during stair ascent when compared to the controls. For stair descent, the DPN group demonstrated a significant increase in knee and hip ROM in the frontal plane, and also hip ROM in the transverse plane. No significant differences between the groups were identified for joint variability. Conclusions: People with DPN demonstrate alterations in dynamic range of motion at the lower limb joints during stair ascent and descent. The degree of angular movement utilised for both stair tasks was decreased at the ankle joint and this has the potential to undermine balance and stability. In contrast, angular movement at the knee and hip joints was increased in the frontal and transverse planes. This may compensate for impaired balance and stability by increasing the base of support to maintain balance and assist in foot clearance and placement. The specific combination of increased angular movement at the knee and hip may represent a compensatory stair gait strategy in response to reduced angular movement at the ankle joint
Digital ethical Bildung as a proactive educational approach against cyberbullying, with Aristotle, Løgstrup and Barad as sources for a philosophical framework
No full textThis article discusses three different theoretical approaches to deal with cyberbullying in education in ethics. The first approach is Tom Harrison’s fostering of “cyber-phronesis”, based on Aristotelian virtue ethics. The second one is K. E. Løgstrup’s ontological ethics which focuses on self-evident ethical demands emerging when people get entangled with each other. The third is Karen Barad’s agential realism, which also focuses on entanglements but includes more than humans in what matters as entangled agents. This opens for the inclusion of cyberspace in both technical, material and social manners as ethical agents. The author finds all three approaches viable and believes that they can be combined. Digital ethical Bildung (close to ‘cyber-phronesis’) of children is important in order to refrain from bullying others and to sustain bullying. Face-to-face entanglements is a better environment to become ethically addressed than online in order to enhance one’s phronesis. Considering non-human ethical agents is viable in order to be aware of and enhance one’s digital ethical Bildung further
Buscando mi tonal: a queer Chicano's search for self in academic literature
No full textIncludes bibliographical references (pages 172-190)This thesis attempts to challenge notions about queer Chicanos, contextualize their lives within Chicano/ Latino communities (and in the broader communities in which we exist) and dispute stereotypical, and harmful ideas about queer Chicanos, our families, and lives. It does this by conducting content analysis on Mesoamerican and Chicano Studies literature and presenting and highlighting work by Queer Chicanas/os and contributing the author???s auto-historia as a counter-narrative. A second goal of this thesis to examine and contribute to the academic discussion related to queer/ gay Chicano men by using a relational theory focused on sex and desire as proposed by Yvonne Yarbro-Bejarano, (2010) and borrow and expand on the concepts of mestizaje and nepantlism as presented by Gloria Anzaldua (1987) in Borderlands/ La Frontera. The image of a lost and diseased queer Chicano/ Latinos is countered in this thesis by the idea of Queer Chicano in the process of healing and finding a home in their families and cultures
Probing renal pH using hyperpolarized [1-13C]alaninamide
No full textHyperpolarized molecular probes can be effectively used as pH markers. To date, the only two probes reported in vivo as extracellular pH sensors are 13C-bicarbonate, and [1,5-13C2]zymonic acid. Alaninamide is a derivative of alanine which is found to be sensitive to variations of pH in the physiological range. The aim of the present study was to assess the feasibility of using alaninamide as a pH probe in vivo. The alaninamide titration curve was determined by performing 13C NMR measurements at 9.4 T, 37° on a set of 500 mM Ala-NH2∙HCl samples of varying pH referenced to 13C urea. [1-13C]Alaninamide was polarized at 1 K in a 7 T polarizer, then rapidly dissolved in a buffered solution and injected IV into a Sprague Dawley rat (n=6) located in a 9.4 T animal scanner. 13C FIDs were acquired with 30° BIR4 pulses using a single loop 1H / quadrature 13C surface coil placed over the left kidney. The pH was perturbed by injecting acetazolamide IV (10 mg/kg) one hour prior to infusion. The alaninamide titration curve shows a 13C1 chemical shift change of ≈ 8.4 ppm, and a pKa of 7.9. The pH sensitivity of 13C1 results in three distinct alaninamide spectral peaks, corresponding to three different extracellular pH compartments within the kidney (pH = 7.46, pH = 7.22, pH = 6.58) that can be tentatively assigned to the cortex/blood, medulla and calyx/ureter. With acetazolamide treatment, the pH in the first compartment follows the change in pH of the blood, while the pH in the third compartment does not reflect the urine pH and shifts during the brief experiment. No change is observed in the pH value of the second compartment.LIFMET2018, University of Southampton, A. Radaelli, R. Hata, S. Sando, O. Bonny, A. Comment R. Gruetter, H. A. I. Yoshihara. Oral presentation, last author Alice Radaeli T13, P7
Representations of the First Places of Learning on the Paintings of the Medieval Serbian Monasteries
No full textThe iconography created during the 800-year-long Serbian history depicts the times filled with important historical and cultural events. The frescoes reflect the development of diverse trends in our educational system. The walls of various monasteries depict the lives of the saints and the real events occurring during their life time. Everyday objects used in the medieval Serbia, such as furniture, writing materials, medical instruments, decorations, the attire of the kings, patrons, monks, etc., illustrate the culture of the day.
The aim of the paper is to explore the originality, pedagogical propedeutics, and the beginnings of Serbian education, which was manifested, didactically speaking, in the apparent teaching – this fact is evident in the frescoes and icons of the monasteries and temples. The frescoes, icons and biblical scenes are works of art, but their function is primarily sacral, as well as instructive. The image of a saint on the wall precisely reflected the environment of the saint's life and the message (motto) of his life. The messages conveyed in the frescoes primarily point to the works and wonders of Christ, emphasise the importance of mercy to the other, good deeds that had to be practised, and piety (piety in a sense of living according to God’s rules).
The method used in the paper is the biblical-iconographic approach, and the author also relied on the instructive elements represented in the lives of the saints and demonstrated in the personalities of the saints interpreted in an interdisciplinary way: from the artistic, technical-decorative, ecclesiastical-aesthetical, and historical perspectives
Cerebrospinal Fluid Aβ43 Is Reduced in Early-Onset Compared to Late-Onset Alzheimer’s Disease, But Has Similar Diagnostic Accuracy to Aβ42
No full textBackground: Amyloid beta 1–43 (Aβ43) may be a useful additional biomarker for diagnosing Alzheimer’s disease (AD). We have investigated cerebrospinal fluid (CSF) levels of Aβ43 in patients with early-onset AD in contrast to levels in late-onset AD. For comparison, in addition to the ‘core’ biomarkers, several other analytes were also determined [YKL-40, neurofilament light (NF-L), glial fibrillary acidic protein (GFAP), and progranulin].
Material and Methods: Cerebrospinal fluid samples were obtained from patients with early-onset AD (age ≤ 62, n = 66), late-onset AD (age ≥ 68, n = 25), and groups of cognitively intact individuals (age ≤ 62, n = 41, age ≥ 68, n = 39). Core CSF AD biomarkers [amyloid beta 1–42 (Aβ42), total tau, phosphorylated tau] were analyzed, as well as levels of Aβ43 and other analytes, using commercially available enzyme-linked immunosorbent assays.
Results: Cerebrospinal fluid Aβ43 was significantly reduced in early-onset AD compared to late-onset AD (14.8 ± 7.3 vs. 21.8 ± 9.4 pg/ml, respectively), whereas the levels of Aβ42 in the two AD groups were not significantly different (474.9 ± 142.0 vs. 539.6 ± 159.9 pg/ml, respectively). Aβ43 and all core biomarkers were significantly altered in patients with AD compared to corresponding controls. NF-L was significantly increased in early-onset AD compared to younger controls, an effect not found between the older groups. Relationships between the Aβ peptides and tau proteins, YKL-40, NF-L, GFAP and progranulin were also investigated without finding marked associations. However, age-associated increases in levels of tau proteins, YKL-40, NF-L and GFAP were found with respect to age in healthy controls. Results for these other analytes were similar to previously published data. Aβ43 did not improve diagnostic accuracy in either AD group compared to Aβ42. Discussion: Cerebrospinal fluid Aβ43, but not Aβ42 levels, varied significantly with age in patients with AD. If CSF levels of Aβ peptides reflect amyloid deposition in brain, the possibility arises that there is a difference between Aβ43 and Aβ42 deposition in younger compared to older brain. However, the level of Aβ43 in CSF shows no improvement over Aβ42 regarding diagnostic accuracy.publishedVersion© 2017 Lauridsen, Sando, Møller, Berge, Pomary, Grøntvedt, Salvesen, Bråthen and White. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer's disease, mild cognitive impairment, or healthy controls: a two year follow-up study
No full textBackground
α-Synuclein has been proposed as a potential biomarker for Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, results from α-synuclein measurements in cerebrospinal fluid (CSF) have been inconclusive, and to our knowledge, longitudinal studies of changes prior to the AD diagnosis have not been investigated.
Methods
Levels of α-synuclein at baseline and after one and two years were measured in CSF, by enzyme-linked immunosorbent assay. Twenty-six patients with early AD (AD-AD), 48 patients with aMCI, subdivided as 23 that developed AD during follow-up (MCI-AD), and 25 that did not (MCI-MCI), and 25 healthy control individuals, were included. One-way ANOVA was applied to compare mean α-synuclein baseline values between all four study groups, and a linear mixed model was used to compare mean change over time between the three patient groups. Linear associations between α-synuclein and amyloid-β 1–42 (Aβ42), amyloid-β 1–40 (Aβ40), total tau and phosphorylated tau were also examined.
Results
A large variation in individual α-synuclein CSF levels was observed, particularly in the MCI-AD group. No significant differences were found in mean α-synuclein levels between all the study groups at baseline. When using a linear mixed model, no significant differences were found at follow-up for estimated mean changes between the patient groups. MCI-AD patients with short duration of symptoms prior to inclusion in the study (≤2 years) had considerably higher mean CSF α-synuclein levels compared to patients with a longer symptom duration (802.2 vs. 442.8 pg/mL, p = 0.01). No such difference was seen in the MCI-MCI or AD-AD groups. Significant linear associations (p < 0.0005) between α-synuclein and Aβ40, total tau and phosphorylated tau were found.
Conclusion
The observed difference in mean CSF α-synuclein level according to duration of symptoms in the MCI-AD group, may be an indication of changes related to disease progression. However, the lack of significant differences between groups, as well as the large individual variation in CSF levels of α-synuclein in the present study, suggest that α-synuclein is not a useful biomarker for AD.© 2016 The Author(s).Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
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