Comparison of focal macular cone ERGs in complete-type congenital stationary night blindness and APB-treated monkeys

AbstractFocal macular cone electroretinograms (ERGs) and multifocal ERGs were recorded to study the macular function in patients with the complete-type of congenital stationary night blindness (cCSNB). The waveforms of the focal macular cone ERGs and the on- and off-responses of the multifocal ERGs in the cCSNB patients were similar to those recorded from monkey retinas treated with L-2 amino-4-phosphonobutyric acid (APB), suggesting that patients with cCSNB have a complete defect of the on-pathway even in the central retina. The results also demonstrated that there was a paradoxical positive response in the central retina of cCSNB patients, as compared to the negative full-field ERGs in the same subjects

Transposon Ac/Ds-induced chromosomal rearrangements at the rice OsRLG5 locus

Previous studies have shown that pairs of closely-linked Ac/Ds transposable elements can induce various chromosomal rearrangements in plant genomes. To study chromosomal rearrangements in rice, we isolated a line (OsRLG5-161) that contains two inversely-oriented Ds insertions in OsRLG5 (Oryza sativa Receptor like kinase Gene 5). Among approximately 300 plants regenerated from OsRLG5-161 heterozygous seeds, 107 contained rearrangements including deletions, duplications and inversions of various sizes. Most rearrangements were induced by previously identified alternative transposition mechanism. Furthermore, we also detected a new class of rearrangements that contain juxtaposed inversions and deletions on the same chromosome. We propose that these novel alleles were generated by a previously unreported type of alternative transposition reactions involving the 5′ and 3′ termini of two inversely-oriented Ds elements located on the same chromatid. Finally, 11% of rearrangements contained inversions resulting from homologous recombination between the two inverted Ds elements in OsRLG5-161. The high frequency inheritance and great variety of rearrangements obtained suggests that the rice regeneration system results in a burst of transposition activity and a relaxation of the controls which normally limit the transposition competence of individual Ds termini. Together, these results demonstrate a greatly enlarged potential of the Ac/Ds system for plant chromosome engineering

An Inflationary Scenario Taking into Account of Possible Dark Energy Effects in the Early Universe

We investigate the possible effect of cosmological-constant type dark energy during the inflation period of the early universe. This is accommodated by a new dispersion relation in de Sitter space. The modified inflation model of a minimally-coupled scalar field is still able to yield an observation-compatible scale-invariant primordial spectrum, simultaneously having potential to generate a spectrum with lower power at large scales. A qualitative match to the WMAP 7-year data is presented. We obtain an $\Omega_\Lambda$ of the same order of that in the $\Lambda$-CDM model. Possible relations between the de Sitter scenario and the Doubly Special Relativity(DSR) are also discussed.Comment: 17 pages, 3 figuire

Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke

Importance Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to −4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, −1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was −1.5%, which is larger than the −4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration ClinicalTrials.gov Identifier: NCT0366141

Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation

A functional genetic screen using loss-of-function and gain-of-function alleles was performed to identify modifiers of tau-induced neurotoxicity using the 2N/4R (full-length) isoform of wild-type human tau expressed in the fly retina. We previously reported eye pigment mutations, which create dysfunctional lysosomes, as potent modifiers; here, we report 37 additional genes identified from ∼1900 genes screened, including the kinases shaggy/GSK-3beta, par-1/MARK, CamKI and Mekk1. Tau acts synergistically with Mekk1 and p38 to down-regulate extracellular regulated kinase activity, with a corresponding decrease in AT8 immunoreactivity (pS202/T205), suggesting that tau can participate in signaling pathways to regulate its own kinases. Modifiers showed poor correlation with tau phosphorylation (using the AT8, 12E8 and AT270 epitopes); moreover, tested suppressors of wild-type tau were equally effective in suppressing toxicity of a phosphorylation-resistant S11A tau construct, demonstrating that changes in tau phosphorylation state are not required to suppress or enhance its toxicity. Genes related to autophagy, the cell cycle, RNA-associated proteins and chromatin-binding proteins constitute a large percentage of identified modifiers. Other functional categories identified include mitochondrial proteins, lipid trafficking, Golgi proteins, kinesins and dynein and the Hsp70/Hsp90-organizing protein (Hop). Network analysis uncovered several other genes highly associated with the functional modifiers, including genes related to the PI3K, Notch, BMP/TGF-β and Hedgehog pathways, and nuclear trafficking. Activity of GSK-3β is strongly upregulated due to TDP-43 expression, and reduced GSK-3β dosage is also a common suppressor of Aβ42 and TDP-43 toxicity. These findings suggest therapeutic targets other than mitigation of tau phosphorylation

Development of Amperometric Hydrogen Peroxide Sensor Based on Horseradish Peroxidase-Immobilized Poly(Thiophene-co-EpoxyThiophene)

A modified electrode for hydrogen peroxide (H2O2) sensing was prepared via thiophene (Th) with epoxy group. Thiophene (EpoxyTh) with epoxy group was synthesized by reaction of 3-bromothiophene and glycidyl methacrylate (GMA) in acetonitrile according to Heck Reaction. The electrocopolymerization of Th and EpoxyTh was performed on the surface of indium tin oxide (ITO) electrode by cycling the potential between -1.0 and +2.5 V in mixture of thiophene (Th) and EpoxyTh. Poly(Th-co- EpoxyTh) grown onto the ITO electrode was successfully confirmed by SEM, AFM, and water contact angle analysis, respectively. Finally, the HRP was immobilized on the surface of poly(Th-co-EpoxyTh) electrode by covalent binding. The amperometric response of the HRP-immobilized poly(Th-co-EpoxyTh) electrode for H2O2 was examined by cyclic voltammetry (CV). The HRP-immobilized poly(Th-co-EpoxyTh) electrode showed linearity from 0.1 to 30 mM H2O2, good reproducibility, and long life time

Mangiferin Alleviates Ovalbumin-Induced Allergic Rhinitis via Nrf2/HO-1/NF-κB Signaling Pathways

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR