Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer's Disease Progression

Total tau (t‐tau) and phosphorylated tau (p‐tau) protein elevations in cerebrospinal fluid (CFS) are well‐established hallmarks of Alzheimer’s disease (AD), while the associations of serum t‐tau and p‐tau levels with AD have been inconsistent across studies. To identify more accessible non‐invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age‐matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild‐AD group (n = 20) according to the Mini‐mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t‐tau, but not p‐tau, was significantly higher in the mild‐AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t‐tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild‐AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell‐derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood‐brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t‐tau and p‐tau (S202) were significantly higher in the mild‐AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ1–42) was lower in the mild‐AD group compared to MCI groups (p < 0.001). During the 4‐year follow‐up, NEX t‐tau and p‐tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t‐tau and p‐tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

Effects of a Dehydroevodiamine-Derivative on Synaptic Destabilization and Memory Impairment in the 5xFAD, Alzheimer's Disease Mouse Model

Carboxy-dehydroevodiamine·HCl (cx-DHED) is a derivative of DHED, which improves memory impairment. Carboxyl modification increases solubility in water, indicating that its bioavailability is higher than that of DHED. Cx-DHED is expected to have better therapeutic effects on Alzheimer's disease (AD) than DHED. In this study, we investigated the therapeutic effects of cx-DHED and the underlying mechanism in 5xFAD mice, transgenic (Tg) mouse model of AD model mice. In several behavioral tests, such as Y-maze, passive avoidance, and Morris water maze test, memory deficits improved significantly in cx-DHED-treated transgenic (Tg) mice compared with vehicle-treated Tg mice. We also found that AD-related pathologies, including amyloid plaque deposition and tau phosphorylation, were reduced after the treatment of Tg mice with cx-DHED. We determined the levels of synaptic proteins, such as GluN1, GluN2A, GluN2B, PSD-95 and Rabphilin3A, and Rab3A in the brains of mice of each group and found that GluN2A and PSD-95 were significantly increased in the brains of cx-DHED-treated Tg mice when compared with the brains of Tg-vehicle mice. These results suggest that cx-DHED has therapeutic effects on 5xFAD, AD model mice through the improvement of synaptic stabilization

An Examination of the Predictive Validity of Early Literacy Measures for Korean English Language Learners

The primary aim of this study was to examine the predictive validity of early literacy measures with Korean English language learners (ELLs) representing varying levels of English language proficiency. First-grade Korean ELLs (N = 102) were screened in the winter using measures of Phoneme Segmentation Fluency (PSF), Nonsense Word Fluency (NWF), and Word Identification Fluency (WIF). Spring reading criterion measures included Oral Reading Fluency (ORF) and the Woodcock Reading Mastery Tests (WRMT). Among the winter screening measures, WIF was found to be most correlated with end-of-the year reading outcomes for the larger sample, as well for students aggregated by language proficiency groups. While moderate to high correlations were also found for winter NWF with respect to spring outcomes, correlations were much smaller in magnitude for winter PSF. Results of hierarchical regression models, with PSF, NWF, and WIF entered respectively, also found that the addition of WIF resulted in a large and significant change in R2 with respect to both spring ORF and WRMT scores. Final models accounted for a total of 75.6% of the variance in spring ORF scores and 60.4% of the variance in WRMT scores. Furthermore, of the winter screening measures, only winter WIF was found to be significant at the p < 0.05 level in both of the final models. Finally, an examination of the diagnostic accuracy of PSF and NWF at-risk cutoffs established by the Dynamic Indicators of Basic Early Literacy Skills (DIBELS) yielded negative predictive values at or above 85% for all tests with respect to spring outcomes; however, positive predictive values were significantly lower, ranging from 17% to 47%. Although past studies have found that many of the same assessments tools that have been used with native English speakers can be used with ELLs, the results of this study indicate that there is a need for the continued development of decision rules and appropriate assessment tools that are sensitive to the unique cultural and linguistic backgrounds of ELLs

An Examination of the Predictive Validity of Early Literacy Measures for Korean English Language Learners

The primary aim of this study was to examine the predictive validity of early literacy measures with Korean English language learners (ELLs) representing varying levels of English language proficiency. First-grade Korean ELLs (N = 102) were screened in the winter using measures of Phoneme Segmentation Fluency (PSF), Nonsense Word Fluency (NWF), and Word Identification Fluency (WIF). Spring reading criterion measures included Oral Reading Fluency (ORF) and the Woodcock Reading Mastery Tests (WRMT). Among the winter screening measures, WIF was found to be most correlated with end-of-the year reading outcomes for the larger sample, as well for students aggregated by language proficiency groups. While moderate to high correlations were also found for winter NWF with respect to spring outcomes, correlations were much smaller in magnitude for winter PSF. Results of hierarchical regression models, with PSF, NWF, and WIF entered respectively, also found that the addition of WIF resulted in a large and significant change in R2 with respect to both spring ORF and WRMT scores. Final models accounted for a total of 75.6% of the variance in spring ORF scores and 60.4% of the variance in WRMT scores. Furthermore, of the winter screening measures, only winter WIF was found to be significant at the p < 0.05 level in both of the final models. Finally, an examination of the diagnostic accuracy of PSF and NWF at-risk cutoffs established by the Dynamic Indicators of Basic Early Literacy Skills (DIBELS) yielded negative predictive values at or above 85% for all tests with respect to spring outcomes; however, positive predictive values were significantly lower, ranging from 17% to 47%. Although past studies have found that many of the same assessments tools that have been used with native English speakers can be used with ELLs, the results of this study indicate that there is a need for the continued development of decision rules and appropriate assessment tools that are sensitive to the unique cultural and linguistic backgrounds of ELLs

Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer’s Disease Progression

Total tau (t-tau) and phosphorylated tau (p-tau) protein elevations in cerebrospinal fluid (CFS) are well-established hallmarks of Alzheimer’s disease (AD), while the associations of serum t-tau and p-tau levels with AD have been inconsistent across studies. To identify more accessible non-invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age-matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild-AD group (n = 20) according to the Mini-mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t-tau, but not p-tau, was significantly higher in the mild-AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t-tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild-AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell-derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood-brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t-tau and p-tau (S202) were significantly higher in the mild-AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ1–42) was lower in the mild-AD group compared to MCI groups (p < 0.001). During the 4-year follow-up, NEX t-tau and p-tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t-tau and p-tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression

Effect of methyl substitution on the diketopyrrolopyrrole-based semiconducting polymers for organic thin film transistors

Two semiconducting polymers, poly[2,5-bis(5-octylpentadecyl)-3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4( 2H,5H)-dione-selenophene] (PDPP-Se) and poly[3,6-bis(4-methylthiophen-2-yl)-2,5-bis(5-octylpentadecyl)pyrrolo[3,4-c] pyrrole-1,4(2H, 5H)-dione-selenophene] (PMDPP-Se) were designed and synthesized. These polymers contain diketopyrrolopyrrole (DPP) and methyl-substituted DPP (MDPP) units as the acceptor building blocks, and selenophene as a counter donor unit. The introduction of methyl groups on the thiophene units flanked by the DPP core substantially affected its optical, electrochemical, and charge-transporting properties. Experimental results revealed that the introduction of electron-donating methyl groups raised the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of PMDPP-Se. Interestingly, the PMDPP-Se showed better co-planarity with the adjacent aromatic groups compared to PDPP-Se. Furthermore, the methyl-substituted polymer showed a transition behavior in its thin film morphology and crystal orientation with an increase in the annealing temperature, which induced an M-shape dependence of the field-effect mobility on the annealing temperature. PMDPP-Se recorded a maximum hole mobility mu(h) = 1.31 cm(2) V-1 s(-1) at optimum phase, which is higher than that of PDPP-Se (mu(h) = 0.86 cm(2) V-1 s(-1)).11Nsciescopu

Baicalein prevents 6-hydroxydopamine-induced dopaminergic dysfunction and lipid peroxidation in mice

The effects of baicalein on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were evaluated. Intracerebroventricularly (i.c.v.) injection of 6-OHDA was done to young mice. Baicalein was administered intraperitoneally 30 min before and 90 min after i.c.v. injection. Animals received further injection of bacalein daily for 3 consecutive days. Rotarod performance was assessed, tyrosine hydroxylase (TH) Western blotting was performed, and dopamine (DA) levels and peroxidation were determined. High dose of baicalein effectively improved rotarod performance and prevented the reduction of striatal DA levels and TH contents in the striatum and subtantia nigra (SN). In addition, lipid peroxidation level was decreased by baicalein at 3 and 7 days after 6-OHDA injection. These results showed that baicalein effectively prevents the 6-OHDA-induced dopaminergic dysfunction through an antioxidative action

Electric current-induced precipitation hardening in advanced high-strength steel

Effect of electric current on precipitation hardening for advanced high-strength steel is investigated based on mechanical testing and microscopic observation. Complex-phase steel containing nano-sized Nb-bearing carbides was used. By comparing the flow stress between uniaxial tension with applied electric current (pulsed tension) and without electric current (nonpulsed tension) at various elevated temperatures, the influence of electric current on precipitation hardening was confirmed. A higher values of Vickers hardness and full-width-at-half-maximum were obtained in the pulsed tensile specimen compared to the identically heat treated specimen after the same deformation. Small angle neutron scattering analysis showed that the volume fraction and mean diameter of newly formed precipitates in the pulsed tensile specimen were higher and larger than those in the induction heat treated specimen, respectively. It clearly shows that additional precipitation hardening could be induced by the athermal effect of electric current, which is distinct from the thermal effect of Joule heating.N