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Youth experiencing suicidal thoughts and/or behaviors (STBs) frequently present to emergency departments for acute psychiatric care. These settings offer a transitory yet pivotal opportunity to assess, intervene on, and plan continued care for STBs. This study examined a clinically relevant, understudied aspect of psychological functioning among youth experiencing STBs in the emergency department: episodic future thinking, or the ability to imagine discrete autobiographical future events. A sample of 167 youths (10-17 years) presenting to a pediatric psychiatric emergency department for STBs completed a performance-based measure of episodic future thinking assessing richness in detail and subjective characteristics of imagined future events. STB recurrence was assessed 6 months later. Immediately following a suicide-related crisis, youth demonstrated mixed abilities to imagine their future: they generated some concrete future event details but did not subjectively perceive these events as being very detailed or likely to occur. Older adolescents (i.e., 15-17) generated more episodic details than pre-/younger adolescents (i.e., 10-14), particularly those pertaining to actions or sensory perceptions. There was no evidence linking less detailed episodic future thinking and greater likelihood of STBs following the emergency department visit; instead, hopelessness was a more robust risk factor. Findings underscore the importance and clinical utility of better understanding the psychological state of youth during or immediately following a suicide-related crisis. In particular, assessing youths' future thinking abilities in the emergency department may directly inform approaches to acute care delivery.
Assuntos
Ideação Suicida , Suicídio , Criança , Humanos , Adolescente , Fatores de Risco , Serviço Hospitalar de Emergência , PsicoterapiaRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients. Out of 417 articles screened, 47 studies were selected for analysis. Among exosomal protein biomarkers, α-synuclein, tau, Amyloid ß 1-42, and C-X-C motif chemokine ligand 12 (CXCL12) were identified as significant markers for PD. Concerning miRNA biomarkers, miRNA-24, miR-23b-3p, miR-195-3p, miR-29c, and mir-331-5p are promising across studies. α-synuclein exhibited increased levels in PD patients compared to control groups in twenty-one studies, while a decrease was observed in three studies. Our meta-analysis revealed a significant difference in total exosomal α-synuclein levels between PD patients and healthy controls (standardized mean difference [SMD] = 1.369, 95% confidence interval [CI] = 0.893 to 1.846, p < 0.001), although these results are limited by data availability. Furthermore, α-synuclein levels significantly differ between PD patients and healthy controls (SMD = 1.471, 95% CI = 0.941 to 2.002, p < 0.001). In conclusion, certain exosomal proteins and multiple miRNAs could serve as potential biomarkers for diagnosis, prognosis prediction, and assessment of disease progression in PD.
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Biomarcadores , Exossomos , MicroRNAs , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/sangue , Doença de Parkinson/genética , Exossomos/metabolismo , Exossomos/genética , Biomarcadores/sangue , MicroRNAs/sangue , MicroRNAs/genética , alfa-Sinucleína/sangue , Peptídeos beta-Amiloides/sangueRESUMO
Nonsense-mediated mRNA decay (NMD), an mRNA quality control process, is thought to function in plant immunity. A subset of fully spliced (FS) transcripts of Arabidopsis (Arabidopsis thaliana) resistance (R) genes are upregulated during bacterial infection. Here, we report that 81.2% and 65.1% of FS natural TIR-NBS-LRR (TNL) and CC-NBS-LRR transcripts, respectively, retain characteristics of NMD regulation, as their transcript levels could be controlled posttranscriptionally. Both bacterial infection and the perception of bacteria by pattern recognition receptors initiated the destruction of core NMD factors UP-FRAMESHIFT1 (UPF1), UPF2, and UPF3 in Arabidopsis within 30 min of inoculation via the independent ubiquitination of UPF1 and UPF3 and their degradation via the 26S proteasome pathway. The induction of UPF1 and UPF3 ubiquitination was delayed in mitogen-activated protein kinase3 (mpk3) and mpk6, but not in salicylic acid-signaling mutants, during the early immune response. Finally, previously uncharacterized TNL-type R transcripts accumulated in upf mutants and conferred disease resistance to infection with a virulent Pseudomonas strain in plants. Our findings demonstrate that NMD is one of the main regulatory processes through which PRRs fine-tune R transcript levels to reduce fitness costs and achieve effective immunity.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Degradação do RNAm Mediada por Códon sem Sentido/genética , Moléculas com Motivos Associados a Patógenos/metabolismo , Imunidade Vegetal , Proteólise , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Autoimunidade/genética , Regulação da Expressão Gênica de Plantas , Sistema de Sinalização das MAP Quinases , Mutação/genética , Pseudomonas/patogenicidade , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , UbiquitinaçãoRESUMO
PURPOSE: To evaluate the efficacy of COMORAL a new multi-channeled oral irrigation (MCOI) unit with pulsating water jet, in plaque score reduction and gingivitis. METHODS: This was a single-blinded clinical randomized controlled trial (NCT05031260). Forty-two healthy subjects between 18 to 35 years old were initially recruited, and the control group (n = 20) and the intervention group (n = 17) were randomly assigned. Both groups were asked to brush their teeth one or two times a day without any supplementary oral hygiene products while the intervention group used COMORAL 3 times a day, 5 days a week. Clinical indices including gingival index (GI), plaque index (PI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR), and clinical attachment loss (CAL) were obtained at the baseline (D0), day 14 (D14), and day 28 (D28). Saliva was collected to examine the presence of periodontal pathogens. The repeated measures analysis of variance or generalized estimating equation was used to compare the interaction between groups and time points. The independent t-test or Mann-Whitney test were used for intergroup differences at each time point. RESULTS: At V0, PI, GI, BOP, and PD scores showed no differences between the two groups. At V1 and V2, these scores showed significant difference between two groups (P < 0.05) such that the intervention group showed gradual decreases while the control group showed no change. There were no differences in GR, CAL, and periodontal pathogens between the two groups. COMORAL showed improvement in reducing gingival inflammation and dental plaque formation adjuvant to routine toothbrushing in healthy adults. CLINICAL SIGNIFICANCE: The results of this study can be useful to clinicians when selecting oral hygiene devices that can help improve patients' routine oral hygiene practice and their overall oral health.
Assuntos
Placa Dentária , Gengivite , Adulto , Humanos , Adolescente , Adulto Jovem , Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Higiene Bucal , Escovação Dentária , Método Simples-Cego , Índice de Placa DentáriaRESUMO
Major depressive disorder (MDD) is a highly prevalent psychiatric condition affecting an estimated 280 million individuals globally. Despite the occurrence of suicidal behaviors across various psychiatric conditions, MDD is distinctly associated with the highest risk of suicide attempts and death within this population. In this study, we focused on MDD to identify potential inflammatory biomarkers associated with suicidal risk, given the relationship between depressive states and suicidal ideation. Articles published before June 2023 were searched in PubMed, Embase, Web of Science, and the Cochrane Library to identify all relevant studies reporting blood inflammatory biomarkers in patients with MDD with suicide-related behaviors. Of 571 articles, 24 were included in this study. Overall, 43 significant biomarkers associated with MDD and suicide-related behaviors were identified. Our study provided compelling evidence of significant alterations in peripheral inflammatory factors in MDD patients with suicide-related behaviors, demonstrating the potential roles of interleukin (IL)-1ß, IL-6, C-reactive protein, C-C motif chemokine ligand 2, and tumor necrosis factor-α as biomarkers. These findings underscore the intricate relationship between the inflammatory processes of these biomarkers and their interactions in MDD with suicidal risk.
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We recently developed a multiplex diagnostic kit, QPLEX™ Alz plus assay kit, which captures amyloid-ß1-40, galectin-3 binding protein, angiotensin-converting enzyme, and periostin simultaneously using microliters of peripheral blood and utilizes an optimized algorithm for screening Alzheimer's disease (AD) by correlating with cerebral amyloid deposition. Owing to the demand for early AD detection, we investigate the potential of our kit for the early clinical diagnosis of AD. A total of 1395 participants were recruited, and their blood samples were analyzed with the QPLEX™ kit. The average of QPLEX™ algorithm values in each group increased gradually in the order of the clinical progression continuum of AD: cognitively normal (0.382 ± 0.150), subjective cognitive decline (0.452 ± 0.130), mild cognitive impairment (0.484 ± 0.129), and AD (0.513 ± 0.136). The algorithm values between each group showed statistically significant differences among groups divided by Mini-Mental State Examination and Clinical Dementia Rating. The QPLEX™ algorithm values could be used to distinguish the clinical continuum of AD or cognitive function. Because blood-based diagnosis is more accessible, convenient, and cost- and time-effective than cerebral spinal fluid or positron emission tomography imaging-based diagnosis, the QPLEX™ kit can potentially be used for health checkups and the early clinical diagnosis of AD.
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Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Humanos , Doença de Alzheimer/metabolismo , Testes Neuropsicológicos , Disfunção Cognitiva/complicações , Cognição , Transtornos Cognitivos/etiologia , Tomografia por Emissão de Pósitrons , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Progressão da DoençaRESUMO
Suicide screening is critical in pediatric emergency departments (EDs). Behavioral measures of suicide risk may complement self-report measures. The current study examines suicide-specific behavioral measures and tests their potential short-term within-person effects among respondents, ability to discriminate future suicide attempt from suicidal ideation, and translation into interpretable categorical composite scores. The sample included 167 youth (10-17 years), presenting for suicide-related reasons to a pediatric psychiatric ED. During their ED visit, participants completed the Death/Life Implicit Association Test (IAT) and the Suicide Stroop Task. Recurrent suicidal thoughts and attempts were assessed within 6 months of the ED visit via medical records and email surveys. Youth displayed a decrease in the levels of distress and self-injurious desires (negative mood, desire to hurt themselves, and desire to die) after completing the behavioral tasks. The Death/Life IAT prospectively differentiated with 68% accuracy between youth who attempted suicide after their ED visit and those who had suicidal ideation but no attempt, p = 0.04, OR = 5.65, although this effect became marginally significant after controlling for self-report and demographic covariates. Neither the Suicide Stroop Task, nor the categorical composite scores predicted suicide attempts, ps = 0.08-0.87, ORs = 0.96-3.95. Behavioral measures of suicide risk administered in the ED do not appear to increase distress or self-injurious desires. They may be able to distinguish those who go on to attempt suicide (vs. consider suicide) within six months after discharge.
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A nuclear serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) is a critical regulator of development and DNA damage response. HIPK2 can induce apoptosis under cellular stress conditions and thus its protein level is maintained low by constant proteasomal degradation. In the present study, we present evidence that TNF receptor-associated factor 2 (TRAF2) regulates the protein stability of HIPK2. Overexpression of TRAF2 decreased while its knockdown increased the HIPK2 protein level. The TRAF2-mediated decrease in HIPK2 protein expression was blocked by proteasomal inhibitor. In addition, TRAF2 decreased the protein half-life of HIPK2. We found that HIPK2 and TRAF2 co-immunoprecipitated. Interestingly, the co-immunoprecipitation was reduced while HIPK2 protein level increased following TNFα treatment, suggesting TNFα induced dissociation of TRAF2 from HIPK2 to accumulate HIPK2. Inhibition of HIPK2 partially suppressed TNFα-induced cell death, indicating that the accumulated HIPK2 may contribute to the TNFα-induced cell death. Our results suggest that TRAF2 can regulate proapoptotic function of HIPK2 by promoting proteasomal degradation.
Assuntos
Proteínas Serina-Treonina Quinases , Fator de Necrose Tumoral alfa , Apoptose , Proteínas Serina-Treonina Quinases/genética , Estabilidade Proteica , Fator 2 Associado a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Recently, we reported that auditory fear conditioning leads to the presynaptic potentiation at lateral amygdala to basal amygdala (LA-BA) synapses that shares the mechanism with high-frequency stimulation (HFS)-induced long-term potentiation (LTP) ex vivo. In the present study, we further examined the molecular mechanisms underlying the HFS-induced presynaptic LTP. We found that a presynaptic elevation of Ca2+ was required for the LTP induction. Interestingly, the blockade of presynaptic but not postsynaptic HCN channels with ZD7288 completely abolished LTP induction. While ZD7288 did not alter basal synaptic transmission, the blocker fully reversed previously established LTP, indicating that HCN channels are also required for the maintenance of LTP. Indeed, HCN3 and HCN4 channels were preferentially localized in the presynaptic boutons of LA afferents. Furthermore, an inhibition of either GABAB receptors or GIRK channels eliminated the inhibitory effect of HCN blockade on the LTP induction. Collectively, we suggest that activation of presynaptic HCN channels may counteract membrane hyperpolarization during tetanic stimulation, and thereby contributes to the presynaptic LTP at LA-BA synapses.
Assuntos
Complexo Nuclear Basolateral da Amígdala , Potenciação de Longa Duração , Sinapses , Transmissão Sináptica , Terminações Pré-SinápticasRESUMO
Guanine nucleotide binding protein (G protein) gamma 8 (Gng8) is a subunit of G proteins and expressed in the medial habenula (MHb) and interpeduncular nucleus (IPN). Recent studies have demonstrated that Gng8 is involved in brain development; however, the roles of Gng8 on cognitive function have not yet been addressed. In the present study, we investigated the expression of Gng8 in the brain and found that Gng8 was predominantly expressed in the MHb-IPN circuit of the mouse brain. We generated Gng8 knockout (KO) mice by CRISPR/Cas9 system in order to assess the role of Gng8 on cognitive function. Gng8 KO mice exhibited deficiency in learning and memory in passive avoidance and Morris water maze tests. In addition, Gng8 KO mice significantly reduced long-term potentiation (LTP) in the hippocampus compared to that of wild-type (WT) mice. Furthermore, we observed that levels of acetylcholine (ACh) and choline acetyltransferase (ChAT) in the MHb and IPN of Gng8 KO mice were significantly decreased, compared to WT mice. The administration of nAChR α4ß2 agonist A85380 rescued memory impairment in the Gng8 KO mice, suggesting that Gng8 regulates cognitive function via modulation of cholinergic activity. Taken together, Gng8 is a potential therapeutic target for memory-related diseases and/or neurodevelopmental diseases.
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Habenula , Acetilcolina , Animais , Aprendizagem , Aprendizagem em Labirinto , Camundongos , Camundongos Knockout , Agonistas NicotínicosRESUMO
DYRK1A, one of the dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), plays an important role in various biological processes by regulating downstream targets via kinase-dependent and independent mechanisms. Here, we report a novel role of DYRK1A in maintaining tumor growth and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC) cells. Deletion of DYRK1A from OSCC cells abrogated their in vivo tumorigenicity and self-renewal capacity, the key features of cancer stem-like cells (CSCs; also referred to as tumor-initiating cells). The DYRK1A deletion also induced the suppression of CSC populations and properties, such as migration ability and chemoresistance. Conversely, ectopic expression of DYRK1A in OSCC cells augmented their CSC phenotype. Among five DYRK members (DYRK1A, 1B, 2, 3, and 4), DYRK1A is the most dominantly expressed kinase, and its expression is upregulated in OSCC compared to normal oral epithelial cells. More importantly, DYRK1A was highly enriched in various CSC-enriched OSCC populations compared to their corresponding non-CSC populations, indicating its pivotal role in cancer progression and stemness. Further, our study revealed that fibroblast growth factor 2 (FGF2) is a key regulator in the DYRK1A-mediated CSC regulation. Functional studies demonstrated that the loss of DYRK1A inhibits CSC phenotype via reduction of FGF2. Overexpression of DYRK1A promotes CSC phenotype via upregulation of FGF2. Our study delineates a novel mechanism of cancer stemness regulation by DYRK1A-FGF2 axis in OSCC. Thus, inhibition of DYRK1A would lead to a potential novel therapeutic option for targeting CSCs in OSCC.
Assuntos
Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Orofaríngeas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Humanos , Camundongos , Camundongos Nus , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases DyrkRESUMO
OBJECTIVES: Using two intensive longitudinal data sets with different timescales (90 minutes, daily), we examined emotion network density, a metric of emotional inflexibility, as a predictor of clinical-level anxiety and depression. DESIGN: Mobile-based intensive longitudinal assessments. METHODS: 119 participants (61 anxious and depressed, 58 healthy controls) completed ecological momentary assessment (EMA) to rate a variety of negative (NE) and positive emotions (PE) 9 times per day for 8 days using a mobile phone application. 169 participants (97 anxious and depressed and 72 healthy controls) completed an online daily diary on their NE and PE for 50 days. Multilevel vector autoregressive models were run to compute NE and PE network densities in each data set. RESULTS: In the EMA data set, both NE and PE network densities significantly predicted participants' diagnostic status above and beyond demographics and the mean and standard deviation of NE and PE. Greater NE network density and lower PE network density were associated with anxiety and depression diagnoses. In the daily diary data set, NE and PE network densities did not significantly predict the diagnostic status. CONCLUSIONS: Greater inflexibility of NE and lower inflexibility of PE, indexed by emotion network density, are potential clinical markers of anxiety and depressive disorders when assessed at intra-daily levels as opposed to daily levels. Considering emotion network density, as well as the mean level and variability of emotions in daily life, may contribute to diagnostic prediction of anxiety and depressive disorders. PRACTITIONER POINTS: Emotion network density, or the degree to which prior emotions predict and influence current emotions, indicates an inflexible or change-resistant emotion system. Emotional inflexibility or change resistance over a few hours, but not daily, may characterize anxiety and depressive disorders. Inflexible negative emotion systems are associated with anxiety and depressive disorders, whereas inflexible positive emotion systems may indicate psychological health. Considering emotional inflexibility within days may provide additional information beyond demographics and mean level and variability of emotions in daily life for detecting anxiety and depressive disorders.
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Depressão , Avaliação Momentânea Ecológica , Ansiedade , Biomarcadores , Emoções , HumanosRESUMO
Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.
Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , HumanosRESUMO
Alcohol consumption is associated with an increased risk of several cancers, including oral/oropharyngeal squamous cell carcinoma (OSCC). Alcohol also enhances the progression and aggressiveness of existing cancers; however, its underlying molecular mechanism remains elusive. Especially, the local carcinogenic effects of alcohol on OSCC in closest contact with ingestion of alcohol are poorly understood. We demonstrated that chronic ethanol exposure to OSCC increased cancer stem cell (CSC) populations and their stemness features, including self-renewal capacity, expression of stem cell markers, ALDH activity, and migration ability. The ethanol exposure also led to a significant increase in aerobic glycolysis. Moreover, increased aerobic glycolytic activity was required to support the stemness phenotype of ethanol-exposed OSCC, suggesting a molecular coupling between cancer stemness and metabolic reprogramming. We further demonstrated that chronic ethanol exposure activated NFAT (nuclear factor of activated T cells) signaling in OSCC. Functional studies revealed that pharmacological and genetic inhibition of NFAT suppressed CSC phenotype and aerobic glycolysis in ethanol-exposed OSCC. Collectively, chronic ethanol exposure promotes cancer stemness and aerobic glycolysis via activation of NFAT signaling. Our study provides a novel insight into the roles of cancer stemness and metabolic reprogramming in the molecular mechanism of alcohol-mediated carcinogenesis.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Etanol/metabolismo , Etanol/toxicidade , Regulação Neoplásica da Expressão Gênica , Glicólise , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/patologia , Células-Tronco Neoplásicas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
The lateral amygdala (LA) is a main sensory input site from the cortical and thalamic regions. In turn, LA glutamatergic pyramidal neurons strongly project to the basal amygdala (BA). Although it is well known that auditory fear conditioning involves synaptic potentiation in the LA, it is not clear whether the LA-BA synaptic transmission is modified upon auditory fear conditioning. Here we found that high-frequency stimulation ex vivo resulted in long-term potentiation (LTP) with a concomitant enhancement of neurotransmitter release at LA-BA synapses. Auditory fear conditioning also led to the presynaptic facilitation at LA-BA synapses. Meanwhile, AMPA/NMDA current ratio was not changed upon fear conditioning, excluding the involvement of postsynaptic mechanism. Notably, fear conditioning occluded electrically induced ex vivo LTP in the LA-BA pathway, indicating that the conditioning and electrically induced LTP share common mechanisms. Our findings suggest that the presynaptic potentiation of LA-BA synapses may be involved in fear conditioning.
Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Neurotransmissores/metabolismo , Sinapses/fisiologia , Estimulação Acústica , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/citologia , Complexo Nuclear Basolateral da Amígdala/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Neurônios/citologia , Neurônios/metabolismo , Neurônios/fisiologia , Ratos Sprague-Dawley , Receptores de AMPA/metabolismo , Receptores de AMPA/fisiologia , Sinapses/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
In this work, we develop a Ag@Al2O3@Ag plasmonic core-shell-satellite (PCSS) to achieve highly sensitive and reproducible surface-enhanced Raman spectroscopy (SERS) detection of probe molecules. To fabricate PCSS nanostructures, we employ a simple hierarchical dewetting process of Ag films coupled with an atomic layer deposition (ALD) method for the Al2O3 shell. Compared to bare Ag nanoparticles, several advantages of fabricating PCSS nanostructures are discovered, including high surface roughness, high density of nanogaps between Ag core and Ag satellites, and nanogaps between adjacent Ag satellites. Finite-difference time-domain (FDTD) simulations of the PCSS nanostructure confirm an enhancement in the electromagnetic field intensity (hotspots) in the nanogap between the Ag core and the satellite generated by the Al2O3 shell, due to the strong core-satellite plasmonic coupling. The as-prepared PCSS-based SERS substrate demonstrates an enhancement factor (EF) of 1.7 × 107 and relative standard deviation (RSD) of ~7%, endowing our SERS platform with highly sensitive and reproducible detection of R6G molecules. We think that this method provides a simple approach for the fabrication of PCSS by a solid-state technique and a basis for developing a highly SERS-active substrate for practical applications.
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Óxido de Alumínio/química , Nanopartículas Metálicas/química , Prata/química , Análise Espectral RamanRESUMO
PARP-1 is a multifunctional enzyme that regulates DNA repair, chromatin remodeling, inflammation and cell survival. Our previous study revealed that PARP-1 is required for maintaining normal level of neural stem cell proliferation. In the present study, we present evidence indicating that PARP-1 regulates neural stem cell proliferation by upregulating the expression of platelet-derived growth factor receptor α (PDGFRα). PARP-1 knockout neural stem cells exhibited striking downregulation of PDGFRα expression. We found that PARP-1 promotes the transcription of PDGFRα independently of its enzymatic activity. Overexpression of PDGFRα in the PARP-1 knockout neural stem cells reversed the proliferation defect of the knockout cells. Conversely, knockdown or blocking antibody of PDGFRα suppressed the proliferation of neural stem cells. In addition, blockade of PDGFRα increased cell death rate. Consistent with the downregulation of PDGFRα in the absence of PARP-1, PDGF-AA promoted proliferation of wild-type neural stem cells but not that of PARP-1 knockout cells. These results suggest that PARP-1 can control the neural stem cell proliferation by regulating the expression of PDGFRα.
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Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo/genética , Ligantes , Camundongos , Camundongos Endogâmicos C57BLRESUMO
To evaluate the seasonal water circulation of Tonle Sap Lake and its tributary rivers in Cambodia, the spatial distribution patterns of major and trace elements in surface water were investigated. Based on the similarity of the dissolved elemental concentrations, the water samples were mainly divided into the three groups: samples with relatively high percentages of Ca, Mo, and Sb (Subcluster B1); samples with high Si, Al, and Fe (B2); and samples with high Na, K, and Mg (B3). During the rainy season, the elemental composition of lake water (B1) appeared to be greatly influenced by the intrusion of water from the Mekong River (B1) through the Tonle Sap River (B1). During the dry season, the type of lake water shifted to B3, suggesting that the lake water stored during the rainy season was replaced by inflow from other tributaries and groundwater in its vicinity. Thus, the seasonal changes in the elemental composition of the lake water were largely controlled by surface water and groundwater circulation. The dissolved As concentration was higher in the lake water and during the dry season than that in the river water and during the rainy season, indicating the discharge of As from the lake's bottom sediment during the dry season. Although the redox cycling of Fe and Mn appeared to be less important due to the shallow water depth in the lake, there are potential risks of As poisoning induced by the formation of an anoxic water mass and increment in the concentration of phosphorus if eutrophication continues to progress.
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Oligoelementos , Poluentes Químicos da Água/análise , Camboja , Monitoramento Ambiental , Lagos , Rios , ÁguaRESUMO
The ventral subiculum (vSub), a representative output structure of the hippocampus, serves as a main limbic region in mediating the brain's response to stress. There are three subtypes of subicular pyramidal neurons based on their firing patterns: regular-spiking (RS), weak-bursting (WB) and strong-bursting (SB) neurons, located differently along proximal-distal axis. Here, we found that chronic social defeat stress (CSDS) in mice increased the population of SB neurons but decreased RS neurons in the proximal vSub. Specific blockers of T-type calcium channels inhibited the burst firings with a concomitant reduction of afterdepolarization, suggesting that T-type calcium channels underlie the burst-spiking activity. Consistently, CSDS increased both T-type calcium currents and expression of Cav3.1 proteins, a subtype of T-type calcium channels, in the proximal vSub. Therefore, we conclude that CSDS-induced enhancement of Cav3.1 expression increased bursting neuronal population in the vSub, which may contribute to stress-related behaviors.
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Potenciais de Ação/fisiologia , Canais de Cálcio Tipo T/metabolismo , Hipocampo/fisiopatologia , Neurônios/fisiologia , Comportamento Social , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Doença Crônica , Hipocampo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacosRESUMO
The ventral subiculum (vSub) is the major output structure of the hippocampus and serves as a main limbic region in mediating the brain's response to stress. Previously, we reported that there are three subtypes of vSub neurons based on their firing patterns: regular-spiking (RS), weak-bursting (WB) and strong-bursting (SB) neurons and chronic social defeat stress (CSDS) increased SB neurons especially in the proximal vSub. Here, we found that neurons in the proximal vSub projected to the nucleus accumbens (NAc). CSDS significantly increased SB neurons but decreased RS neurons among the NAc-projecting vSub neuronal population. Interestingly, these changes were only apparent in mice susceptible to CSDS, but not in CSDS-resilient ones. Given that ventral hippocampal inputs to the NAc regulate susceptibility to CSDS, the bursting activity of NAc-projecting vSub neurons might be functionally relevant to behavioral susceptibility to CSDS.