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Analyzing all biological evidence at a crime scene presents serious time, budget, and labor constraints. Therefore, selecting valid evidence is crucial for efficient screening. The ABO blood group is a marker that can serve as valid evidence for identifying investigative leads in criminal case. Conventional identification of ABO blood groups using serological methods has only been for blood and is difficult to apply to other body fluids. ABO genotyping was conducted by analyzing single nucleotide polymorphisms (SNP) representative of each blood group. However, this method is time-consuming, expensive, and requires sophisticated instruments. In this study, we developed rapid ABO genotyping method using loop-mediated isothermal amplification (LAMP) and multiplex real-time polymerase chain reaction (PCR). Three SNP sites in the ABO gene (nt 261, 526, and 803) were selected to classify the ABO genotypes. For the specificity test, we performed sequencing of 60 saliva samples to confirm that the genotyping. We conducted experiments to apply ABO genotyping using two amplification methods to mock forensic sample using cotton swab and filter paper. As a result, using LAMP, we successfully identified six ABO genotypes within 30 min at a constant temperature (65 â). Moreover, by using multiple real-time PCR, it was possible to detect not only the major group but also the subgroup of the ABO genotype (ex. cis-AB). The amplification results using the new methods were in concordance with the sequencing results. Therefore, these ABO genotyping methods are expected to select valid evidence successfully and efficiently at the crime scene.
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Técnicas de Genotipagem , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Genótipo , Técnicas de Genotipagem/métodos , Sistema ABO de Grupos Sanguíneos/genética , Sensibilidade e EspecificidadeRESUMO
This paper explored techniques for diagnosing breast cancer using deep learning based medical image recognition. X-ray (Mammography) images, ultrasound images, and histopathology images are used to improve the accuracy of the process by diagnosing breast cancer classification and by inferring their affected location. For this goal, the image recognition application strategies for the maximal diagnosis accuracy in each medical image data are investigated in terms of various image classification (VGGNet19, ResNet50, DenseNet121, EfficietNet v2), image segmentation (UNet, ResUNet++, DeepLab v3), and related loss functions (binary cross entropy, dice Loss, Tversky loss), and data augmentation. As a result of evaluations through the presented methods, when using filter-based data augmentation, ResNet50 showed the best performance in image classification, and UNet showed the best performance in both X-ray image and ultrasound image as image segmentation. When applying the proposed image recognition strategies for the maximal diagnosis accuracy in each medical image data, the accuracy can be improved by 33.3% in image segmentation in X-ray images, 29.9% in image segmentation in ultrasound images, and 22.8% in image classification in histopathology images.
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Aprendizado Profundo , Neoplasias , Mamografia , Entropia , Reconhecimento PsicológicoRESUMO
In a society centered on hyper-connectivity, information sharing is crucial, but it must be ensured that each piece of information is viewed only by legitimate users; for this purpose, the medium that connects information and users must be able to identify illegal users. In this paper, we propose a smartphone authentication system based on human gait, breaking away from the traditional authentication method of using the smartphone as the medium. After learning human gait features with a convolutional neural network deep learning model, it is mounted on a smartphone to determine whether the user is a legitimate user by walking for 1.8 s while carrying the smartphone. The accuracy, precision, recall, and F1-score were measured as evaluation indicators of the proposed model. These measures all achieved an average of at least 90%. The analysis results show that the proposed system has high reliability. Therefore, this study demonstrates the possibility of using human gait as a new user authentication method. In addition, compared to our previous studies, the gait data collection time for user authentication of the proposed model was reduced from 7 to 1.8 s. This reduction signifies an approximately four-fold performance enhancement through the implementation of filtering techniques and confirms that gait data collected over a short period of time can be used for user authentication.
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Aprendizado Profundo , Smartphone , Humanos , Reprodutibilidade dos Testes , Marcha , CaminhadaRESUMO
The COVID-19 pandemic and related restrictions can impact mental health. To quantify the mental health burden of COVID-19 pandemic, we conducted a systematic review and meta-analysis, searching World Health Organization COVID-19/PsycInfo/PubMed databases (09/29/2020), including observational studies reporting on mental health outcomes in any population affected by COVID-19. Primary outcomes were the prevalence of anxiety, depression, stress, sleep problems, posttraumatic symptoms. Sensitivity analyses were conducted on severe mental health problems, in high-quality studies, and in representative samples. Subgroup analyses were conducted stratified by age, sex, country income level, and COVID-19 infection status. One-hundred-seventy-three studies from February to July 2020 were included (n = 502,261, median sample = 948, age = 34.4 years, females = 63%). Ninety-one percent were cross-sectional studies, and 18.5%/57.2% were of high/moderate quality. The highest prevalence emerged for posttraumatic symptoms in COVID-19 infected people (94%), followed by behavioral problems in those with prior mental disorders (77%), fear in healthcare workers (71%), anxiety in caregivers/family members of people with COVID-19 (42%), general health/social contact/passive coping style in the general population (38%), depression in those with prior somatic disorders (37%), and fear in other-than-healthcare workers (29%). Females and people with COVID-19 infection had higher rates of almost all outcomes; college students/young adults of anxiety, depression, sleep problems, suicidal ideation; adults of fear and posttraumatic symptoms. Anxiety, depression, and posttraumatic symptoms were more prevalent in low-/middle-income countries, sleep problems in high-income countries. The COVID-19 pandemic adversely impacts mental health in a unique manner across population subgroups. Our results inform tailored preventive strategies and interventions to mitigate current, future, and transgenerational adverse mental health of the COVID-19 pandemic.
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COVID-19 , Pandemias , Adulto , COVID-19/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Saúde Mental , Prevalência , SARS-CoV-2 , Adulto JovemRESUMO
We have developed blue- and yellow-emitting two-photon probes (BGolgi-blue and PGolgi-yellow) from 6-(benzo[ d]oxazol-2-yl)-2-naphthalylamine and 2,5-bis(benzo[ d]oxazol-2-yl)pyrazine derivatives as the fluorophores and trans-Golgi-network peptide (SDYQRL) as the Golgi-apparatus-targeting moiety. HeLa cells labeled with BGolgi-blue and PGolgi-yellow emitted two-photon-excited fluorescence at 462 and 560 nm, respectively, with effective two-photon-action cross-section values of 1860 and 1600 × 10-50 cm4·s/photon, respectively. The probes can detect the Golgi apparatus in live cells and deep inside live tissue via two-photon microscopy at widely separated wavelength regions with high selectivity and minimal pH interference, and they are photostable and have low cytotoxicity.
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Benzoxazóis/química , Corantes Fluorescentes/química , Complexo de Golgi/metabolismo , Oligopeptídeos/química , Animais , Apoptose/fisiologia , Benzoxazóis/síntese química , Benzoxazóis/efeitos da radiação , Benzoxazóis/toxicidade , Estabilidade de Medicamentos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Microscopia de Fluorescência/métodos , Oligopeptídeos/síntese química , Oligopeptídeos/efeitos da radiação , Oligopeptídeos/toxicidade , Fótons , Ratos Sprague-DawleyRESUMO
We developed Pyr1-infliximab: a two-photon probe for TNF-α. Pyr1-infliximab showed absorption maxima at 280 and 438 nm and an emission maximum at 610 nm in an aqueous buffer and effective two-photon action cross-section values of (520-2830) × 10-50 cm4s/photon in RAW 264.7 cells. After this probe was labeled, it was possible to detect Pyr1-infliximab-transmembrane TNF-α complexes in a live cell and to determine the relative proportion of these complexes in human colon tissues. This proportion among healthy, possibly inflamed, and inflamed tissues of patients with ulcerative colitis was found to be 1.0/4.5/10. This probe may find useful applications for selective detection of transmembrane TNF-α in a live cell or tissue, for quantification of inflammation in human colon tissue or of antidrug antibodies in patients who stop responding to anti-TNF therapy, and for monitoring of the response to this therapy.
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Colo/metabolismo , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Carbazóis/química , Sobrevivência Celular/efeitos dos fármacos , Colo/patologia , Corantes Fluorescentes/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Infliximab/química , Infliximab/imunologia , Camundongos , Fotólise , Células RAW 264.7 , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologiaRESUMO
We have developed two-photon (TP) pH-sensitive probes (BH-2 and BHEt-1) that exhibit absorption and emission maxima at 370 and 466 nm, and TP absorption cross-section values of 51 and 61 GM (1 GM = 10-50cm4s/photon), respectively, at 750 nm and pH 3.0 in a universal buffer (0.1 M citric acid, 0.1 M KH2PO4, 0.1 M Na2B4O7, 0.1 M Tris, 0.1 M KCl)/1,4-dioxane (7/3) solution. The TPM images of CCD-18co (a normal colon cell line) and HCT116 cells (a colon cancer cell line) labeled with BH-2 were too dim to be distinguished. When the same cells were labeled with BHEt-1, however, the TPM image of the HCT116 cells was much brighter than that of CCD-18co cells, and the relative proportion of the acidic vesicles (Pacid) of the former was 5-fold larger than that of latter. BHEt-1 could also differentiate HepG2 cells (a human liver cancer cell line) from LX-2 cells (a human hepatic stellate cell line) with a 6-fold larger Pacid value. Human colon cancer tissues labeled with BHEt-1 showed similar results, demonstrating much brighter TPM images and 6-fold larger Pacid values compared to normal tissue. These results suggest the potential utility of BHEt-1 for detecting colon cancer in human tissues using TPM.
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Neoplasias do Colo/diagnóstico por imagem , Corantes Fluorescentes/química , Fótons , Linhagem Celular , Corantes Fluorescentes/síntese química , Células HCT116 , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Microscopia de Fluorescência por Excitação Multifotônica , Estrutura MolecularRESUMO
We have developed a two-photon fluorescent tracer (Pyr-affibody) that shows high selectivity for human epidermal growth factor receptor-2 (HER-2). Pyr-affibody showed absorption and emission maxima at 439 and 574 nm, respectively, with a two-photon absorption cross-section value of 40 × 10-50 cm4s/photon (GM) at 750 nm in aqueous buffer solution. The effective two-photon action cross-section value measured in HeLa cells was 600 GM at 730 nm, a value sufficient to obtain bright two-photon microscopy (TPM) images. Using Pyr-affibody, it was possible to detect HER-2 overexpressing cells and breast cancers at a depth of 90-130 µm in live mouse tissue by TPM.
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Benzofuranos/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Corantes Fluorescentes/farmacologia , Pirazinas/farmacologia , Receptor ErbB-2/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Animais , Benzofuranos/síntese química , Benzofuranos/efeitos da radiação , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Humanos , Luz , Camundongos Endogâmicos BALB C , Pirazinas/síntese química , Pirazinas/efeitos da radiação , Proteínas Recombinantes de Fusão/síntese química , Proteínas Recombinantes de Fusão/efeitos da radiaçãoRESUMO
Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don't alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.
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While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Camundongos Transgênicos , Doença de Parkinson , SARS-CoV-2 , Animais , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/virologia , Humanos , COVID-19/patologia , COVID-19/virologia , Doença de Parkinson/patologia , Doença de Parkinson/virologia , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Microglia/patologia , Microglia/metabolismo , Microglia/virologia , Células-Tronco Embrionárias Humanas/metabolismo , Astrócitos/patologia , Astrócitos/virologia , Astrócitos/metabolismo , Encéfalo/patologia , Encéfalo/virologiaRESUMO
Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD. [BMB Reports 2023; 56(3): 178-183].
Assuntos
Doença de Huntington , Camundongos , Animais , Desacetilase 6 de Histona/metabolismo , Doença de Huntington/tratamento farmacológico , Camundongos Transgênicos , Neurônios/metabolismo , Modelos Animais de DoençasRESUMO
The YrdA protein shows high sequence similarity to γ-class carbonic anhydrase (γ-CA) proteins and is classified as part of the γ-CA protein family. However, its function has not been fully elucidated as it lacks several of the conserved residues that are considered to be necessary for γ-CA catalysis. Interestingly, a homologue of γ-CA from Methanosarcina thermophila and a ß-carboxysomal γ-CA from a ß-cyanobacterium have shown that these catalytic residues are not always conserved in γ-CAs. The crystal structure of YrdA from Escherichia coli (ecYrdA) is reported here in two crystallographic forms. The overall structure of ecYrdA is also similar to those of the γ-CAs. One loop around the putative catalytic site shows a number of alternative conformations. A His residue (His70) on this loop coordinates with, or is reoriented from, the catalytic Zn(2+) ion; this is similar to the conformations mediated by an Asp residue on the catalytic loops of ß-CA proteins. One Trp residue (Trp171) also adopts two alternative conformations that may be related to the spatial positions of the catalytic loop. Even though significant CA activity could not be detected using purified ecYrdA, these structural features have potential functional implications for γ-CA-related proteins.
Assuntos
Anidrases Carbônicas/química , Proteínas de Escherichia coli/química , Sítio Alostérico , Sequência de Aminoácidos , Domínio Catalítico , Escherichia coli/enzimologia , Histidina/química , Íons , Ferro/química , Dados de Sequência Molecular , Mutação , Ligação Proteica , Conformação Proteica , Homologia de Sequência de Aminoácidos , Triptofano/química , Zinco/químicaRESUMO
Micropatterning is considered a promising strategy for improving the performance of electrochemical devices. However, micropatterning on ceramic is limited by its mechanically fragile properties. This paper reports a novel imprinting-assisted transfer technique to fabricate an interlayer structure in a protonic ceramic electrochemical cell with a micropatterned electrolyte. A dense proton-conducting electrolyte, BaCe0.7Zr0.1Y0.1Yb0.1O3-δ, is micropatterned in a chevron shape with the highest aspect ratio of patterns in electrode-supported cells to the best of our knowledge, increasing surface areas of both electrode sides more than 40%. The distribution of relaxation time analysis reveals that the chevron-patterned electrolyte layer significantly increases the electrode contact areas and active electrochemical reaction sites at the vicinity of the interfaces, contributing to enhanced performances of both the fuel cell and electrolysis operations. The patterned cell demonstrates improved fuel cell performance (>45%) and enhances electrolysis cell performance (30%) at 500 °C. This novel micropatterning technique is promising for the facile production of layered electrochemical cells, further opening a new route for the performance enhancement of ceramic-based electrochemical cells.
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Developing a method for fabricating high-efficient and low-cost fuel cells is imperative for commercializing polymer electrolyte membrane (PEM) fuel cells (FCs). This study introduces a mechanical and chemical modification technique using the oxygen plasma irradiation process for hydrocarbon-based (HC) PEM. The oxygen functional groups were introduced on the HC-PEM surface through the plasma process in the controlled area, and microsized structures were formed. The modified membrane was incorporated with plasma-treated electrodes, improving the adhesive force between the HC-PEM and the electrode. The decal transfer was enabled at low temperatures and pressures, and the interfacial resistance in the membrane-electrode assembly (MEA) was reduced. Furthermore, the micropillar structured electrode configuration significantly reduced the oxygen transport resistance in the MEA. Various diagnostic techniques were conducted to find out the effects of the membrane surface modification, interface adhesion, and mass transport, such as physical characterizations, mechanical stress tests, and diverse electrochemical measurements.
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Huntington's disease (HD) is a severe inherited neurological disorder caused by a CAG repeat expansion in the huntingtin gene (HTT), leading to the accumulation of mutant huntingtin with polyglutamine repeats. Despite its severity, there is no cure for this debilitating disease. HTT lowering strategies, including antisense oligonucleotides (ASO) showed promising results very recently. Attempts to develop stem cell-based therapeutics have shown efficacy in preclinical HD models. Using an HD patient's autologous cells, which have genetic defects, may hamper therapeutic efficacy due to mutant HTT. Pretreating these cells to reduce mutant HTT expression and transcription may improve the transplanted cells' therapeutic efficacy. To investigate this, we targeted the SUPT4H1 gene that selectively supports the transcription of long trinucleotide repeats. Transplanting SUPT4H1-edited HD-induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) into the YAC128 HD transgenic mouse model improved motor function compared to unedited HD iPSC-NPCs. Immunohistochemical analysis revealed reduced mutant HTT expression without compensating wild-type HTT expression. Further, SUPT4H1 editing increased neuronal and decreased reactive astrocyte differentiation in HD iPSC-NPCs compared to the unedited HD iPSC-NPCs. This suggests that ex vivo editing of SUPT4H1 can reduce mutant HTT expression and provide a therapeutic gene editing strategy for autologous stem cell transplantation in HD.
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Among four types of bacterial restriction enzymes that cleave a foreign DNA depending on its methylation status, type I enzymes composed of three subunits are interesting because of their unique DNA cleavage and translocation mechanisms performed by the restriction subunit (HsdR). The elucidated N-terminal fragment structure of a putative HsdR subunit from Vibrio vulnificus YJ016 reveals three globular domains. The nucleolytic core within an N-terminal nuclease domain (NTD) is composed of one basic and three acidic residues, which include a metal-binding site. An ATP hydrolase (ATPase) site at the interface of two RecA-like domains (RDs) is located close to the probable DNA-binding site for translocation, which is far from the NTD nucleolytic core. Comparison of relative domain arrangements with other functionally related ATP and/or DNA complex structures suggests a possible translocation and restriction mechanism of the HsdR subunit. Furthermore, careful analysis of its sequence and structure implies that a linker helix connecting two RDs and an extended region within the nuclease domain may play a central role in switching the DNA translocation into the restriction activity.
Assuntos
Desoxirribonucleases de Sítio Específico do Tipo I/química , Vibrio vulnificus/enzimologia , Adenosina Trifosfatases/química , Sequência de Aminoácidos , DNA/metabolismo , Clivagem do DNA , Desoxirribonucleases de Sítio Específico do Tipo I/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Subunidades Proteicas/metabolismoRESUMO
OBJECTIVES: To investigate whether human HLA-homozygous induced pluripotent stem cell (iPSC)-derived neural precursor cells (iPSC-NPCs) can provide functional benefits in Huntington's disease (HD), we transplanted them into the YAC128 transgenic HD mouse model. MATERIALS AND METHODS: CHAi001-A, an HLA-homozygous iPSC line (A*33:03-B*44:03-DRB1*13:02), was differentiated into neural precursor cells, and then, they were transplanted into 6 months-old YAC128 mice. Various behavioural and histological analyses were performed for five months after transplantation. RESULTS: Motor and cognitive functions were significantly improved in transplanted animals. Cells transplanted in the striatum showed multipotential differentiation. Five months after transplantation, the donor cells had differentiated into neurons, oligodendrocytes and astrocytes. Transplantation restored DARPP-32 expression, synaptophysin density, myelin basic protein expression in the corpus callosum and astrocyte function. CONCLUSION: Altogether, these results strongly suggest that iPSC-NPCs transplantation induces neuroprotection and functional recovery in a mouse model of HD and should be taken forward for clinical trials in HD patients.
Assuntos
Diferenciação Celular , Doença de Huntington/patologia , Células-Tronco Neurais/transplante , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Comportamento Animal , Linhagem Celular , Corpo Caloso/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Humanos , Doença de Huntington/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Proteína Básica da Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Monoéster Fosfórico Hidrolases/metabolismoRESUMO
The development of a novel approach to achieve high-performance and durable fuel cells is imperative for the further commercialization of proton-exchange (or polymer electrolyte) membrane fuel cells (PEMFCs). In this work, multifunctional dendritic Nafion/CeO2 structures were introduced onto the cathode side of the interface between a membrane and a catalyst layer through electrospray deposition. The dendritic structures enlarged the interfacial contact area between the membrane and the catalyst layer and formed microscale voids between the catalyst layer and gas diffusion medium. This improved the PEMFC performance through the effective utilization of the catalyst and enhanced mass transport of the reactant. Especially, under low-humidity conditions, the hygroscopic effect of CeO2 nanoparticles also boosted the power density of PEMFCs. In addition to the beneficial effects on the efficiency of the PEMFC, the incorporation of CeO2, widely known as a radical scavenger, effectively mitigated the free-radical attack on the outer surface of the membrane, where chemical degradation is initiated by radicals formed during PEMFC operation. These multifunctional effects of the dendritic Nafion/CeO2 structures on PEMFC performance and durability were investigated using various in situ and ex situ measurement techniques.
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We report blue- and green-emitting two-photon probes derived from naphthalene and fluorene derivatives (as fluorophores) and an endoplasmic reticulum (ER) retrieval peptide (KDEL; as an ER-targeting moiety) that can detect the ER in a live cell by both one-photon and two-photon microscopy (TPM) and in a live tissue by TPM.
Assuntos
Retículo Endoplasmático/química , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica , Fótons , Fluorenos/química , Células HeLa , Humanos , Estrutura Molecular , Naftalenos/química , Imagem Óptica , Peptídeos/químicaRESUMO
OBJECTIVES: Huntington's disease (HD) is a devastating neurodegenerative disease caused by polyglutamine (polyQ) expansion in the huntingtin (HTT) gene. Mutant huntingtin (mHTT) is the main cause of HD and is associated with impaired mitochondrial dynamics, ubiquitin-proteasome system and autophagy, as well as tauopathy. In this study, we aimed to establish a new neural stem cell line for HD studies. MATERIALS AND METHODS: YAC128 mice are a yeast artificial chromosome (YAC)-based transgenic mouse model of HD. These mice express a full-length human mutant HTT gene with 128 CAG repeats and exhibit various pathophysiological features of HD. In this study, we isolated a new neural stem cell line from the forebrains of YAC128 mouse embryos (E12.5) and analysed its characteristics using cellular and biochemical methods. RESULTS: Compared to wild-type (WT) NSCs, the YAC128 NSC line exhibited greater proliferation and migration capacity. In addition to mHTT expression, increased intracellular Ca2+ levels and dysfunctional mitochondrial membrane potential were observed in the YAC128 NSCs. YAC128 NSCs had defects in mitochondrial dynamics, including a deficit in mitochondrial axonal transport and unbalanced fusion and fission processes. YAC128 NSCs also displayed decreased voltage response variability and Na+ current amplitude. Additionally, the ubiquitin-proteasome and autophagy systems were impaired in the YAC128 NSCs. CONCLUSIONS: We have established a new neural stem line from YAC128 transgenic mice, which may serve as a useful resource for studying HD pathogenesis and drug screening.