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1.
Genome Res ; 34(3): 454-468, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38627094

RESUMO

Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods for accurately phasing Oxford Nanopore Technologies (ONT) sequence data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse. We test using new variants of ONT PromethION sequencing, including those using proximity ligation, and show that newer, higher accuracy ONT reads substantially improve assembly quality.


Assuntos
Nanoporos , Humanos , Análise de Sequência de DNA/métodos , Sequenciamento por Nanoporos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Software , Genômica/métodos
2.
medRxiv ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38585974

RESUMO

Most current studies rely on short-read sequencing to detect somatic structural variation (SV) in cancer genomes. Long-read sequencing offers the advantage of better mappability and long-range phasing, which results in substantial improvements in germline SV detection. However, current long-read SV detection methods do not generalize well to the analysis of somatic SVs in tumor genomes with complex rearrangements, heterogeneity, and aneuploidy. Here, we present Severus: a method for the accurate detection of different types of somatic SVs using a phased breakpoint graph approach. To benchmark various short- and long-read SV detection methods, we sequenced five tumor/normal cell line pairs with Illumina, Nanopore, and PacBio sequencing platforms; on this benchmark Severus showed the highest F1 scores (harmonic mean of the precision and recall) as compared to long-read and short-read methods. We then applied Severus to three clinical cases of pediatric cancer, demonstrating concordance with known genetic findings as well as revealing clinically relevant cryptic rearrangements missed by standard genomic panels.

3.
bioRxiv ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38529488

RESUMO

The combination of ultra-long Oxford Nanopore (ONT) sequencing reads with long, accurate PacBio HiFi reads has enabled the completion of a human genome and spurred similar efforts to complete the genomes of many other species. However, this approach for complete, "telomere-to-telomere" genome assembly relies on multiple sequencing platforms, limiting its accessibility. ONT "Duplex" sequencing reads, where both strands of the DNA are read to improve quality, promise high per-base accuracy. To evaluate this new data type, we generated ONT Duplex data for three widely-studied genomes: human HG002, Solanum lycopersicum Heinz 1706 (tomato), and Zea mays B73 (maize). For the diploid, heterozygous HG002 genome, we also used "Pore-C" chromatin contact mapping to completely phase the haplotypes. We found the accuracy of Duplex data to be similar to HiFi sequencing, but with read lengths tens of kilobases longer, and the Pore-C data to be compatible with existing diploid assembly algorithms. This combination of read length and accuracy enables the construction of a high-quality initial assembly, which can then be further resolved using the ultra-long reads, and finally phased into chromosome-scale haplotypes with Pore-C. The resulting assemblies have a base accuracy exceeding 99.999% (Q50) and near-perfect continuity, with most chromosomes assembled as single contigs. We conclude that ONT sequencing is a viable alternative to HiFi sequencing for de novo genome assembly, and has the potential to provide a single-instrument solution for the reconstruction of complete genomes.

4.
Plants (Basel) ; 13(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38337952

RESUMO

The growing beekeeping industry in South Korea has led to the establishment of new honey plant complexes. However, studies on honey production from each species are limited. This study aimed to assess the honey production potential of various Brassica napus cultivars and two wildflower species. The nectar characteristics of B. napus varied significantly among the cultivars. Absolute sugar concentrations differed among the cultivars, but sugar composition ratios were similar. In contrast, the amino acid content remained relatively uniform regarding percentage values, irrespective of the absolute concentrations. Estimations of honey potential production per hectare (kg/ha) resulted in the following ranking among cultivars: 'JM7003' (107.1) > 'YS' (73.0) > 'JM7001' (63.7) > 'TL' (52.7) > 'TM' (42.4). The nectar volume of Pseudolysimachion rotundum var. subintegrum and Leonurus japonicus increased during the flowering stage. P. rotundum var. subintegrum was sucrose-rich and L. japonicus was sucrose-dominant. Both species predominantly contained phenylalanine, P. rotundum var. subintegrum had glutamine as the second most abundant amino acid, and L. japonicus had tyrosine. The honey production potential was 152.4 kg/ha for P. rotundum var. subintegrum and 151.3 kg/ha for L. japonicus. These findings provide a basis for identifying food resources for pollinators and selecting plant species to establish honey plant complexes.

5.
Am J Case Rep ; 25: e941221, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38234083

RESUMO

BACKGROUND Myositis is an inflammatory myopathy that can be caused by a variety of drugs, diseases, and toxins. The U.S. military uses chemoprophylaxis with intramuscular penicillin G to prevent group A streptococcal infection. We present a case of penicillin G-induced myositis, a rare cause of drug-induced myositis with limited discussion in the medical literature. CASE REPORT A 25-year-old man with no pertinent medical history presented to the Emergency Department with right hip and leg pain after receiving a single dose of intramuscular penicillin G as part of standard prophylaxis for group A streptococcal infection during basic military training. He reported pain and leg weakness that was exacerbated by physical exertion and weight bearing but had no systemic symptoms, such as fevers or chills. Initial radiographs of the hip were normal; however, subsequent magnetic resonance imaging of the hip revealed intramuscular edema and features consistent with myositis of the right proximal thigh and hip musculature. He was admitted for isolated right gluteal myositis, attributed to his preceding local penicillin injection. He recovered with symptomatic care over the following 2 weeks, with return to baseline function. CONCLUSIONS This case highlights a rare complication of intramuscular penicillin G as a cause of acute isolated myositis. It serves to inform physicians of this rare complication and to recommend the consideration of intramuscular penicillin G as a causative etiology in individuals presenting with myositis and recent penicillin G exposure.


Assuntos
Militares , Miosite , Infecções Estreptocócicas , Masculino , Humanos , Adulto , Penicilina G Benzatina/efeitos adversos , Quimioprevenção , Infecções Estreptocócicas/tratamento farmacológico , Dor , Injeções Intramusculares/efeitos adversos , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/tratamento farmacológico
6.
Adv Mater ; 36(14): e2309183, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38160321

RESUMO

Development of miniaturized thin-film lithium-ion batteries (TF-LIBs) using vacuum deposition techniques is crucial for low-scale applications, but addressing low energy density remains a challenge. In this work, structures analogous to SiOx-based thin-film electrodes are designed with close resemblance to traditional LIB slurry formulations including active material, conductive agent, and binder. The thin-film is produced using mid-frequency sputtering with a single hybrid target consisting of SiOx nanoparticles, carbon nanotubes, and polytetrafluoroethylene. The thin-film SiOx/PPFC (plasma-polymerized fluorocarbon) involves a combination of SiOx and conductive carbon within the PPFC matrix. This results in enhanced electronic conductivity and superior elasticity and hardness in comparison to a conventional pure SiOx-based thin-film. The electrochemical performance of the half-cell consisting of thin-film SiOx/PPFC demonstrates remarkable cycling stability, with a capacity retention of 74.8% up to the 1000th cycle at 0.5 C. In addition, a full cell using the LiNi0.6Co0.2Mn0.2O2 thin-film as the cathode material exhibits an exceptional initial capacity of ≈120 mAh g-1 at 0.1 C and cycle performance, marked by a capacity retention of 90.8% from the first cycle to the 500th cycle at a 1 C rate. This work will be a stepping stone for the AM/CB/B composite electrodes in TF-LIBs.

7.
Org Lett ; 25(50): 9008-9013, 2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-38084750

RESUMO

This study presents a Pd(II)-catalyzed method for the ß-C(sp3)-H arylation of N-Cbz- or N-Fmoc-protected N-methyl alanines, providing ready access to building blocks for N-methylated peptide synthesis. For this transformation, the native carboxylate was exploited as the directing group, attributing its success to the use of a monoprotected amino-pyridine ligand. Its synthetic utility was demonstrated by facile generation of nine analogues of the naturally occurring N-methylated cyclic peptide cycloaspeptide A.


Assuntos
Alanina , Paládio , Catálise , Ácidos Carboxílicos , Peptídeos
8.
ACS Appl Mater Interfaces ; 15(47): 54923-54932, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37916291

RESUMO

Polyimide is actively applied in various industrial fields because of its strong mechanical properties, owing to the interactions between the polymer chains. Fully aromatic imide structures exhibit high glass-transition temperatures due to the strong interactions between their chains, which hinder chain mobility. Therefore, preparing a material that exhibits self-healing at a low temperature of ≤100 °C and good mechanical properties is challenging. Thus, we prepared imides with four-component semiaromatic structures by adjusting the contents of 4,4'-(hexafluoroisopropylidene)diphthalic anhydride and 4,4'-(4,4'-isopropylidenediphenoxy)bis(phthalic anhydride) to yield four-component self-healable colorless polyimides (f-SH-CPIs) with novel structures, flexibilities, good mechanical properties, and low healing temperatures. The flexibilities and distances between the polymer chains, as the basis of the trade-off relationship between the mechanical properties and healing efficiency, were controlled. These materials may be used as substrates in wearable devices and multilayer insulation that may protect from space dust, cosmic rays, and satellite fragments.

9.
Front Psychol ; 14: 1264994, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965654

RESUMO

Objectives: This study examined whether older adults with hearing loss (HL) experience greater difficulties in auditory sentence comprehension compared to those with typical-hearing (TH) when the linguistic burdens of syntactic complexity were systematically manipulated by varying either the sentence type (active vs. passive) or sentence length (3- vs. 4-phrases). Methods: A total of 22 individuals with HL and 24 controls participated in the study, completing sentence comprehension test (SCT), standardized memory assessments, and pure-tone audiometry tests. Generalized linear mixed effects models were employed to compare the effects of sentence type and length on SCT accuracy, while Pearson correlation coefficients were conducted to explore the relationships between SCT accuracy and other factors. Additionally, stepwise regression analyses were employed to identify memory-related predictors of sentence comprehension ability. Results: Older adults with HL exhibited poorer performance on passive sentences than on active sentences compared to controls, while the sentence length was controlled. Greater difficulties on passive sentences were linked to working memory capacity, emerging as the most significant predictor for the comprehension of passive sentences among participants with HL. Conclusion: Our findings contribute to the understanding of the linguistic-cognitive deficits linked to age-related hearing loss by demonstrating its detrimental impact on the processing of passive sentences. Cognitively healthy adults with hearing difficulties may face challenges in comprehending syntactically more complex sentences that require higher computational demands, particularly in working memory allocation.

10.
Front Psychol ; 14: 1199682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022929

RESUMO

This study investigated the relative efficacy of interleaved versus blocked instruction and the role of executive function in governing learning from these instructional sequences. Eighth grade students learned about three rock concepts (igneous, sedimentary, metamorphic) and their attributes (origin, texture, composition). Consistent with prior studies and as predicted by current theoretical accounts, students who received interleaved instruction showed better memory (i.e., accuracy on true-false questions) when tested 2 weeks later, whereas those who received blocked instruction showed better memory when tested on the same day as instruction. Also consistent with prior studies and theoretical accounts, the blocked group showed greater transfer when tested after a retention interval, although this advantage was not significant. Critically, and as predicted, the shifting and inhibition executive function abilities were more predictive of learning from interleaved vs. blocked instruction. These findings lay the groundwork for future studies investigating the role of executive function in learning from different forms of instruction.

11.
ACS Appl Mater Interfaces ; 15(40): 47229-47237, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37782228

RESUMO

Neuromorphic computing, an innovative technology inspired by the human brain, has attracted increasing attention as a promising technology for the development of artificial intelligence systems. This study proposes synaptic transistors with a Li1-xAlxTi2-x(PO4)3 (LATP) layer to analyze the conductance modulation linearity, which is essential for weight mapping and updating during on-chip learning processes. The high ionic conductivity of the LATP electrolyte provides a large hysteresis window and enables linear weight update in synaptic devices. The results demonstrate that optimizing the LATP layer thickness improves the conductance modulation and linearity of synaptic transistors during potentiation and degradation. A 20 nm-thick LATP layer results in the most nonlinear depression (αd = -6.59), whereas a 100 nm-thick LATP layer results in the smallest nonlinearity (αd = -2.22). Additionally, a device with the optimal 100 nm-thick LATP layer exhibits the highest average recognition accuracy of 94.8% and the smallest fluctuation, indicating that the linearity characteristics of a device play a crucial role in weight update during learning and can significantly affect the recognition accuracy.

12.
Metabolism ; 148: 155693, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37741434

RESUMO

BACKGROUND & AIMS: Autophagy-related 14 (ATG14) is a key regulator of autophagy. ATG14 is also localized to lipid droplet; however, the function of ATG14 on lipid droplet remains unclear. In this study, we aimed to elucidate the role of ATG14 in lipid droplet homeostasis. METHODS: ATG14 loss-of-function and gain-of-function in lipid droplet metabolism were analyzed by fluorescence imaging in ATG14 knockdown or overexpression hepatocytes. Specific domains involved in the ATG14 targeting to lipid droplets were analyzed by deletion or site-specific mutagenesis. ATG14-interacting proteins were analyzed by co-immunoprecipitation. The effect of ATG14 on lipolysis was analyzed in human hepatocytes and mouse livers that were deficient in ATG14, comparative gene identification-58 (CGI-58), or both. RESULTS: Our data show that ATG14 is enriched on lipid droplets in hepatocytes. Mutagenesis analysis reveals that the Barkor/ATG14 autophagosome targeting sequence (BATS) domain of ATG14 is responsible for the ATG14 localization to lipid droplets. Co-immunoprecipitation analysis illustrates that ATG14 interacts with adipose triglyceride lipase (ATGL) and CGI-58. Moreover, ATG14 also enhances the interaction between ATGL and CGI-58. In vitro lipolysis analysis demonstrates that ATG14 deficiency remarkably decreases triglyceride hydrolysis. CONCLUSIONS: Our data suggest that ATG14 can directly enhance lipid droplet breakdown through interactions with ATGL and CGI-58.


Assuntos
Lipase , Gotículas Lipídicas , Camundongos , Animais , Humanos , Lipase/metabolismo , Gotículas Lipídicas/metabolismo , 1-Acilglicerol-3-Fosfato O-Aciltransferase/genética , 1-Acilglicerol-3-Fosfato O-Aciltransferase/metabolismo , Lipólise , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Homeostase , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo
13.
Sci Rep ; 13(1): 12710, 2023 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-37543713

RESUMO

While zero-phase lag synchronization between multiple brain regions has been widely observed, relatively recent reports indicate that systematic phase delays between cortical regions reflect the direction of communications between cortical regions. For example, it has been suggested that a non-zero phase delay of electroencephalography (EEG) signals at the gamma frequency band between the bilateral parietal areas may reflect the direction of communication between these areas. We hypothesized that the direction of communication between distant brain areas might be modulated by multi-site transcranial alternating current stimulation (tACS) with specific phase delays other than 0° and 180°. In this study, a new noninvasive brain stimulation (NIBS) method called multi-site multi-phase tACS (msmp-tACS) was proposed. The efficacy of the proposed method was tested in a case study using a visuospatial working memory (VWM) paradigm in which the optimal stimulation conditions including amplitudes and phases of multiple scalp electrodes were determined using finite element analysis adopting phasor representation. msmp-tACS was applied over the bilateral intraparietal sulci (IPS) and showed that 80 Hz tACS with the phase for the right IPS leading that for the left IPS by 90° (= 3.125 ms) partialized VWM performance toward the right visual hemifield. The three stimulation conditions were synchronized, RL, and LR, which refers to stimulation condition with no phase lag, stimulation phase of right IPS (rIPS) leading left IPS (lIPS) by 90° and the stimulation of lIPS leading rIPS by 90°, respectively. The lateralization of VWM significantly shifted towards right visual hemifield under the RL condition compared to the synchronized and LR conditions. The shift in VWM was the result of the stimulation affecting both left and right visual hemifield trials to certain degrees, rather than significantly increasing or decreasing VWM capacity of a specific visual hemifield. Altered brain dynamics caused by msmp-tACS partialized VWM performance, likely due to modulation of effective connectivity between the rIPS and lIPS. Our results suggest that msmp-tACS is a promising NBS method that can effectively modulate cortical networks that cannot be readily modulated with conventional multi-site stimulation methods.


Assuntos
Memória de Curto Prazo , Estimulação Transcraniana por Corrente Contínua , Estimulação Transcraniana por Corrente Contínua/métodos , Lobo Parietal/fisiologia , Eletroencefalografia , Cognição
14.
Behav Brain Funct ; 19(1): 13, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620941

RESUMO

BACKGROUND: Cross-frequency phase-amplitude coupling (PAC) of cortical oscillations is observed within and across cortical regions during higher-order cognitive processes. Particularly, the PAC of alpha and gamma waves in the occipital cortex is closely associated with visual perception. In theory, gamma oscillation is a neuronal representation of visual stimuli, which drives the duty cycle of visual perception together with alpha oscillation. Therefore, it is believed that the timing of entrainment in alpha-gamma PAC may play a critical role in the performance of visual perception. We hypothesized that transcranial alternating current stimulation (tACS) with gamma waves entrained at the troughs of alpha waves would enhance the dynamic visual acuity (DVA). METHOD: We attempted to modulate the performance of DVA by using tACS. The waveforms of the tACS were tailored to target PAC over the occipital cortex. The waveforms contained gamma (80 Hz) waves oscillating at either the peaks or troughs of alpha (10 Hz) waves. Participants performed computerized DVA task before, immediately after, and 10 min after each stimulation sessions. EEG and EOG were recorded during the DVA task to assess inter-trial phase coherence (ITPC), the alpha-gamma PAC at occipital site and the eye movements. RESULTS: tACS with gamma waves entrained at alpha troughs effectively enhanced DVA, while the tACS with gamma waves entrained at alpha peaks did not affect DVA performance. Importantly, analyses of EEG and EOG showed that the enhancement of DVA performance originated solely from the neuromodulatory effects, and was not related to the modulation of saccadic eye movements. Consequently, DVA, one of the higher-order cognitive abilities, was successfully modulated using tACS with a tailored waveform. CONCLUSIONS: Our experimental results demonstrated that DVA performances were enhanced when tACS with gamma bursts entrained on alpha wave troughs were applied over the occipital cortex. Our findings suggest that using tACS with tailored waveforms, modulation of complex neuronal features could effectively enhance higher-order cognitive abilities such as DVA, which has never been modulated with conventional noninvasive brain stimulation methods.


Assuntos
Procedimentos Cirúrgicos Refrativos , Estimulação Transcraniana por Corrente Contínua , Humanos , Acuidade Visual , Percepção Visual , Movimentos Oculares
15.
J Comput Chem ; 44(30): 2332-2346, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37585026

RESUMO

Conformational space annealing (CSA), a global optimization method, has been applied to various protein structure modeling tasks. In this paper, we applied CSA to the cryo-EM structure modeling task by combining the python subroutine of CSA (PyCSA) and the fast relax (FastRelax) protocol of PyRosetta. Refinement of initial structures generated from two methods, rigid fitting of predicted structures to the Cryo-EM map and de novo protein modeling by tracing the Cryo-EM map, was performed by CSA. In the refinement of the rigid-fitted structures, the final models showed that CSA can generate reliable atomic structures of proteins, even when large movements of protein domains were required. In the de novo modeling case, although the overall structural qualities of the final models were rather dependent on the initial models, the final models generated by CSA showed improved MolProbity scores and cross-correlation coefficients to the maps. These results suggest that CSA can accomplish flexible fitting and refinement together by sampling diverse conformations effectively and thus can be utilized for cryo-EM structure modeling.


Assuntos
Proteínas , Modelos Moleculares , Microscopia Crioeletrônica/métodos , Proteínas/química , Conformação Molecular , Domínios Proteicos , Conformação Proteica
16.
JAMA Netw Open ; 6(8): e2330024, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37603333

RESUMO

Importance: Evidence of the association between income fluctuation and risk of type 2 diabetes (T2D) is scarce. Objective: To investigate whether sustained low or high income and income changes are associated with incidence of T2D. Design, Setting, and Participants: In this population-based cohort study, more than 7.8 million adults without T2D aged 30 to 64 years from a nationally representative sample from the Korean Health Insurance Service database were enrolled in 2012 and followed up to 2019 (median follow-up, 6.3 years [IQR, 6.1-6.6 years]). Exposures: Twenty quantiles of monthly health insurance premiums determined income levels. Income quartiles were annually analyzed from 2008 to 2012. Beneficiaries of the Medical Aid Program were regarded as those with very low income. A decrease in income was indicated as a reduction of 25% or more in income compared with income in the previous year. Main Outcomes and Measures: The primary outcome was incident T2D based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes E11 to E14, 1 or more claims of antidiabetic medication, or a fasting glucose level of 126 mg/dL or higher. Multivariable Cox proportional hazards models were used to assess the association of low- or high-income status and income changes with incidence of T2D. Results: Of 7 821 227 participants (mean [SD] age, 46.4 [9.3] years; 54.9% men), 359 931 (4.6%) developed T2D at least 1 year after enrollment. Individuals who repeatedly experienced low and very low income for 5 years showed 22% (hazard ratio [HR], 1.22 [95% CI, 1.21-1.23]) and 57% (1.57 [95% CI, 1.53-1.62]) higher T2D risk compared with those who never experienced low and very low income, respectively. In contrast, individuals who were repeatedly in high-income quartiles showed lower T2D risk compared with those who never experienced high income (HR, 0.86 [95% CI, 0.85-0.86]). The number of income decreases was associated with elevated T2D risk (≥2 vs 0 income decreases: HR, 1.08 [95% CI, 1.06-1.11]; P < .001 for trend). When income quartile status was compared between 2008 and 2012, individuals who experienced an income increase had lowered T2D risk, while those who experienced an income decrease had elevated T2D risk in each income quartile group. Conclusions and Relevance: This cohort study found that individuals who experienced sustained low-income status or an income decrease had elevated T2D risk, while those who had sustained high-income status or an income increase had lowered T2D risk.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Estudos de Coortes , Renda , Pobreza , Fatores Socioeconômicos
17.
Front Pharmacol ; 14: 1172269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37261287

RESUMO

Introduction: The receptor for advanced glycation end products (RAGE) and its ligands, such as high-mobility group protein box 1 (HMGB1), play an important role in the accumulation of extracellular matrix in chronic kidney diseases with tubulointerstitial fibrosis. Blocking RAGE signaling with soluble RAGE (sRAGE) is a therapeutic candidate for renal fibrosis. Methods: NRK-52E cells were stimulated with or without HMGB1 and incubated with sRAGE in vitro. Sprague-Dawley rats were intraperitoneally treated with sRAGE after unilateral ureteral obstruction (UUO) operation in vivo. Results: HMBG1-stimulated NRK-52E cells showed increased fibronectin expression, type I collagen, α-smooth muscle actin, and connective tissue growth factor, which were attenuated by sRAGE. The mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of nuclear factor kappa B (NF-κB) were enhanced in NRK-52E cells exposed to HMBG1, and sRAGE treatment alleviated the activation of the MAPK and NF-κB pathways. In the UUO rat models, sRAGE significantly ameliorated the increased renal fibronectin, type I collagen, and α-smooth muscle actin expressions. Masson's trichrome staining confirmed the anti-fibrotic effect of sRAGE in the UUO rat model. RAGE also significantly attenuated the activation of the MAPK pathway and NF-κB, as well as the increased number of infiltrated macrophages within the tubulointerstitium in the kidney of the UUO rat models. Conclusion: These findings suggest that RAGE plays a pivotal role in the pathogenesis of renal fibrosis and that its inhibition by sRAGE may be a potential therapeutic approach for renal fibrosis.

18.
Nat Biotechnol ; 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349522

RESUMO

Progress in understanding brain-viscera interoceptive signaling is hindered by a dearth of implantable devices suitable for probing both brain and peripheral organ neurophysiology during behavior. Here we describe multifunctional neural interfaces that combine the scalability and mechanical versatility of thermally drawn polymer-based fibers with the sophistication of microelectronic chips for organs as diverse as the brain and the gut. Our approach uses meters-long continuous fibers that can integrate light sources, electrodes, thermal sensors and microfluidic channels in a miniature footprint. Paired with custom-fabricated control modules, the fibers wirelessly deliver light for optogenetics and transfer data for physiological recording. We validate this technology by modulating the mesolimbic reward pathway in the mouse brain. We then apply the fibers in the anatomically challenging intestinal lumen and demonstrate wireless control of sensory epithelial cells that guide feeding behaviors. Finally, we show that optogenetic stimulation of vagal afferents from the intestinal lumen is sufficient to evoke a reward phenotype in untethered mice.

19.
Cells ; 12(11)2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-37296621

RESUMO

K2P channels, also known as two-pore domain K+ channels, play a crucial role in maintaining the cell membrane potential and contributing to potassium homeostasis due to their leaky nature. The TREK, or tandem of pore domains in a weak inward rectifying K+ channel (TWIK)-related K+ channel, subfamily within the K2P family consists of mechanical channels regulated by various stimuli and binding proteins. Although TREK1 and TREK2 within the TREK subfamily share many similarities, ß-COP, which was previously known to bind to TREK1, exhibits a distinct binding pattern to other members of the TREK subfamily, including TREK2 and the TRAAK (TWIK-related acid-arachidonic activated K+ channel). In contrast to TREK1, ß-COP binds to the C-terminus of TREK2 and reduces its cell surface expression but does not bind to TRAAK. Furthermore, ß-COP cannot bind to TREK2 mutants with deletions or point mutations in the C-terminus and does not affect the surface expression of these TREK2 mutants. These results emphasize the unique role of ß-COP in regulating the surface expression of the TREK family.


Assuntos
Canais de Potássio de Domínios Poros em Tandem , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Proteína Coatomer/metabolismo
20.
Nanotechnology ; 34(32)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37146599

RESUMO

Ambipolar field-effect transistors (FETs) possessing both electron and hole carriers enable implementation of novel reconfigurable transistors, artificial synaptic transistors, and output polarity controllable (OPC) amplifiers. Here, we fabricated a two-dimensional (2D) material-based complementary ambipolar FET and investigated its electrical characteristics. Properties of ohmic-like contacts at source/drain sides were verified from output characteristics and temperature-dependent measurements. The symmetry of electron and hole currents can be easily achieved by optimization of the MoS2or WSe2channels, different from the conventional ambipolar FET with fundamental issues related to Schottky barriers. In addition, we demonstrated successful operation of a complementary inverter and OPC amplifier, using the fabricated complementary ambipolar FET based on 2D materials.

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