The genetic integrity of iPSCs is an important consideration for therapeutic application. In this study, we examine the accumulation of somatic mitochondrial genome (mtDNA) mutations in skin ...fibroblasts, blood, and iPSCs derived from young and elderly subjects (24–72 years). We found that pooled skin and blood mtDNA contained low heteroplasmic point mutations, but a panel of ten individual iPSC lines from each tissue or clonally expanded fibroblasts carried an elevated load of heteroplasmic or homoplasmic mutations, suggesting that somatic mutations randomly arise within individual cells but are not detectable in whole tissues. The frequency of mtDNA defects in iPSCs increased with age, and many mutations were non-synonymous or resided in RNA coding genes and thus can lead to respiratory defects. Our results highlight a need to monitor mtDNA mutations in iPSCs, especially those generated from older patients, and to examine the metabolic status of iPSCs destined for clinical applications.
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•Human iPSC clones derived from elderly adults show accumulation of mtDNA mutations•Fewer mtDNA mutations are present in ESCs and iPSCs derived from younger adults•Accumulated mtDNA mutations can impact metabolic function in iPSCs
Mitalipov, Huang, and colleagues show that human iPSCs derived from older adults carry more mitochondrial DNA mutations than those derived from younger individuals. Defects in metabolic function caused by mtDNA mutations suggest careful screening of hiPSC clones for mutational load before clinical application.
We investigated the protective effect and mechanisms of apigenin against cognitive impairments in a scopolamine-injected mouse model. Our results showed that intraperitoneal (i.p.) injection of ...scopolamine leads to learning and memory dysfunction, whereas the administration of apigenin (synthetic compound, 100 and 200 mg/kg/day) improved cognitive ability, which was confirmed by behavioral tests such as the T-maze test, novel objective recognition test, and Morris water maze test in mice. In addition, scopolamine-induced lipid peroxidation in the brain was attenuated by administration of apigenin. To further evaluate the protective mechanisms of apigenin on cognitive and memory function, Western blot analysis was carried out. Administration of apigenin decreased the B-cell lymphoma 2-associated X/B-cell lymphoma 2 (Bax/Bcl-2) ratio and suppressed caspase-3 and poly ADP ribose polymerase cleavage. Furthermore, apigenin down-regulated the β-site amyloid precursor protein-cleaving enzyme, along with presenilin 1 (PS1) and PS2 protein levels. Apigenin-administered mice showed lower protein levels of a receptor for advanced glycation end-products, whereas insulin-degrading enzyme, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) expression were promoted by treatment with apigenin. Therefore, this study demonstrated that apigenin is an active substance that can improve cognitive and memory functions by regulating apoptosis, amyloidogenesis, and BDNF/TrkB signaling pathways.
Researchers interested in a paper’s statement or aiming to acquire useful information from scientific papers rely heavily on references. Additionally, calculation accuracy is important for ensuring ...the technical soundness of scientific papers. However, inaccurate citations and calculations are common in scientific literature. A recently published paper in the Journal of Hazardous Materials reported a study on microplastics in groundwater and surface water from coastal south India (Tamil Nadu state) and the heavy metal adsorption capacities of different polymers. In this study, we identified critical calculation errors and incorrect reference citations.
Fourier phase retrieval is a classical problem of restoring a signal only from the measured magnitude of its Fourier transform. Although Fienup-type algorithms, which use prior knowledge in both ...spatial and Fourier domains, have been widely used in practice, they can often stall in local minima. Convex relaxation methods such as PhaseLift and PhaseCut may offer performance guarantees, but these algorithms are usually computationally expensive for practical use. To address this problem, here we propose a novel unsupervised feed-forward neural network for Fourier phase retrieval which generates high quality reconstruction immediately. Unlike the existing deep learning approaches that use a neural network as a regularization term or an end-to-end blackbox model for supervised training, our algorithm is a feed-forward neural network implementation of physics-driven constraints in an unsupervised learning framework. Specifically, our network is composed of two generators: one for the phase estimation using PhaseCut loss, followed by another generator for image reconstruction, all of which are trained simultaneously without matched data. The link to the classical Fienup-type algorithms and the recent symmetry-breaking learning approach is also revealed. Extensive experiments demonstrate that the proposed method outperforms all existing approaches in Fourier phase retrieval problems.
Osteoarthritis (OA) is a degenerative condition of the temporomandibular joint (TMJ) characterised by chronic inflammation and damage to joint structures. Because of the complexity of TMJ-OA, only ...symptomatic treatments are currently available. Recent reports have shown that many of stem cells can exert anti-inflammatory and tissue-regenerating effects. In this study, we investigated the potential cartilage-regenerating and anti-inflammatory effects of human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs) for the treatment of TMJ-OA. hUCM-MSC lines, isolated from different donors, which showed different activities in vitro. Using a selected cell line, we used different concentrations of hUCM-MSCs to assess therapeutic effects in a rabbit model of monosodium iodoacetate-induced TMJ-OA. Compared with the untreated control group, the potential regenerative result and anti-inflammatory effects of hUCM-MSCs were evident at all the tested concentrations in rabbits with induced TMJ-OA. The median dose of hUCM-MSCs showed the prominent cartilage protective effect and further cartilage regeneration potential. This effect occurred via upregulated expression of growth factors, extracellular matrix markers, and anti-inflammatory cytokines, and reduced expression of pro-inflammatory cytokines. The anti-inflammatory effect of hUCM-MSCs was comparable to that of dexamethasone (DEX). However, only hUCM-MSCs showed potential chondrogenesis effects in this study. In conclusion, our results indicate that hUCM-MSCs may be an effective treatment option for the treatment of TMJ-OA.
In this study, lactic acid bacteria were isolated from 21 top-selling probiotic products on Korean market and their antimicrobial resistance were analyzed. A total 152 strains were claimed to be ...contained in these products and 70 isolates belonging to three genera (
,
, and
) were obtained from these products. RAPD-PCR showed diversity among isolates of the same species except for two isolates of
from two different products. The agar dilution method and the broth dilution method produced different MICs for several antimicrobials. With the agar dilution method, five isolates (three isolates of
subsp.
, one isolate of
, one isolate of
) were susceptible to all nine antimicrobials and 15 isolates were multi-drug resistant. With the broth microdilution method, only two isolates (one isolate of
and one isolate of
) were susceptible while 16 isolates were multi-drug resistant. In this study, only two AMR genes were detected: 1)
(A) in one isolate of clindamycin-susceptible and lincomycin-resistant
; and 2)
(W) in one tetracycline-susceptible isolate of
B1-1 and two tetracycline-susceptible isolates and three tetracycline resistant isolates of
subsp.
. Transfer of these two genes via conjugation with a filter mating technique was not observed. These results suggest a need to monitor antimicrobial resistance in newly registered probiotics as well as probiotics with a long history of use.
Autophagy is markedly impaired in Alzheimer's disease (AD). Here we reveal unique autophagy dysregulation within neurons in five AD mouse models in vivo and identify its basis using a neuron-specific ...transgenic mRFP-eGFP-LC3 probe of autophagy and pH, multiplex confocal imaging and correlative light electron microscopy. Autolysosome acidification declines in neurons well before extracellular amyloid deposition, associated with markedly lowered vATPase activity and build-up of Aβ/APP-βCTF selectively within enlarged de-acidified autolysosomes. In more compromised yet still intact neurons, profuse Aβ-positive autophagic vacuoles (AVs) pack into large membrane blebs forming flower-like perikaryal rosettes. This unique pattern, termed PANTHOS (poisonous anthos (flower)), is also present in AD brains. Additional AVs coalesce into peri-nuclear networks of membrane tubules where fibrillar β-amyloid accumulates intraluminally. Lysosomal membrane permeabilization, cathepsin release and lysosomal cell death ensue, accompanied by microglial invasion. Quantitative analyses confirm that individual neurons exhibiting PANTHOS are the principal source of senile plaques in amyloid precursor protein AD models.
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