- Research Article
9
- 10.1016/j.chembiol.2024.12.003
Calcineurin: An essential regulator of sleep revealed by biochemical, chemical biological, and genetic approaches.
- Jan 01, 2025
- Cell chemical biology
- Jianjun Yu + 12 more +12
Publications from 2021 to 2026
Showing 10 of 42 papers
Calcineurin: An essential regulator of sleep revealed by biochemical, chemical biological, and genetic approaches.
2′‐Fucosyllactose Alleviates Hair Loss in Testosterone‐Induced Androgenic Alopecia Mice
2′‐Fucosyllactose (2′‐FL) is a component of human milk oligosaccharides and has undergone extensive investigation for potential health benefits. However, its potential to prevent androgenic alopecia (AGA) has not been reported. In this study, we investigated the protective effect of 2′‐FL on hair damage in a testosterone‐induced AGA mouse model. The administration of 2′‐FL significantly reduced hair loss and increased both hair length and thickness in an AGA mouse model. Mechanistically, administration of 2′‐FL increased hair follicle size and growth factor expression associated with hair growth. 2′‐FL enhanced β‐catenin signaling by activating AKT and ERK. In addition, 2′‐FL suppressed apoptosis signaling and inflammatory cytokines in the dorsal skin of AGA mice. These results underscore the potential of 2′‐FL as a therapeutic agent for AGA.
Read moreDisasters Such as Rockfalls During the Noto Peninsula Earthquake
Development of serum lipoprotein (a) detection using latex enhanced immunoturbidimetry
Abstract Background Lipoprotein (a) (Lp (a)) is indeed a significant factor in cardiovascular health, as it is a product of low-density lipoprotein cholesterol-like particles that bind to apolipoprotein (a). Elevated levels of Lp (a) have been linked to an increased risk of cardiovascular diseases (CVD), hastening disease progression and raising CVD mortality rates. However, the absence of standardized measurement methods for Lp (a) contributes to diagnostic uncertainties. Method A quantitative measurement method for serum Lp (a) was developed using fully automated latex-enhanced particle immunoturbidimetry technology represents a significant advancement in diagnostic capabilities. The key parameters such as repeatability, stability, linearity, and method comparison were evaluated to ensure the accuracy of the assay. Result The Lp (a) in samples was recognized by carboxylated latex particles covalently coated with anti-Lp (a) antibodies. The content of Lp (a) was quantified by measuring the changes in turbidity generated by agglutination at 600 nm. With precision CV% within the batch of 1.10% and inter-batch precision CV% of 1.79%, it demonstrates reliable performance using Randox biochemical quality control samples. The detection limit of 7 mg/L and a high correlation coefficient (R2 = 0.9946) at concentrations of 0-1500 mg/L further validate its effectiveness. Conclusion The quantitative determination method of serum Lp (a) based on latex-enhanced immunoturbidimetric analysis indeed provides rapid results, high accuracy, and automation, making it suitable for routine clinical testing. This method relies on the interaction between Lp (a) and latex particles, allowing for efficient measurement in serum samples.
Read moreLoss modelling from first principles
Abstract A common statistical modelling paradigm used in actuarial pricing is (a) assuming that the possible loss model can be chosen from a dictionary of standard models; (b) selecting the model that provides the best trade-off between goodness of fit and complexity. Machine learning provides a rigorous framework for this selection/validation process. An alternative modelling paradigm, common in the sciences, is to prove the adequacy of a statistical model from first principles: for example, Planck’s distribution, which describes the spectral distribution of blackbody radiation empirically, was explained by Einstein by assuming that radiation is made of quantised harmonic oscillators (photons). In this working party we have been exploring the extent to which loss models, too, can be derived from first principles. Traditionally, the Poisson, negative binomial, and binomial distributions are used as loss count models because they are familiar and easy to work with. We show how reasoning from first principles naturally leads to non-stationary Poisson processes, Lévy processes, and multivariate Bernoulli processes depending on the context. For modelling severities, we build on previous research that shows how graph theory can be used to model property-like losses. We show how the methodology can be extended to deal with business interruption/supply chain risks by considering networks with higher-order dependencies. For liability business, we show the theoretical and practical limitations of traditional models such as the lognormal distribution. We explore the question of where the ubiquitous power-law behaviour comes from, finding a natural explanation in random growth models. We also address the derivation of severity curves in territories where compensation tables are used. This research is foundational in nature, but its results may prove useful to practitioners by guiding model selection and elucidating the relationship between the features of a risk and the model’s parameters.
Read moreProteínas de choque térmico e perfil proteico em Saccharomyces cerevisiae
As leveduras são essenciais em processos biotecnológicos como a produção de bioetanol. Contudo, estes microrganismos enfrentam desafios no ambiente industrial devido a fatores de estresse que podem afetar seu metabolismo. Estas leveduras possuem mecanismos de resposta complexos, incluindo a produção de compostos para autoproteção e a ativação de proteínas de choque térmico (HSPs) para manter a sua integridade celular. Neste sentido, este estudo visa averiguar algumas das proteínas de choque térmico abordando suas características estruturais e molecular, bem como analisar o perfil proteico de linhagens de Saccharomyces cerevisiae industriais sob a ação do estresse térmico. Para tanto, foi realizado um levantamento bibliográfico pertinente ao tema. Concomitante, foi realizado um pré-inoculo em meio liquido de YPD 2% e adicionados 0,10 gramas das leveduras Fleischmann®, Pedra-2, Catanduva-1 e Barra Grande-BG, e incubados a 30 °C por 10 horas a 250 rpm. A biomassa obtida foi inoculada no meio fermentativo em Erlenmeyers de 125 mL, contendo 50 mL de caldo de cana estéril na concentração de 22 ºBrix e pH 5,0, mantidos em incubação a 30ºC e 40ºC a 250rpm. Em diferentes tempos alíquotas de 1000 µL foram coletadas, adicionadas a eppendorfs e centrifugadas. Em seguida, foram adicionados 500µL do tampão TRIS HCl (pH 7) e perolas de vidro para a realização da lise celular. Alíquotas de 100µL das amostras lisadas foram adicionadas a 1000µL de água destilada e 2500µL do reagente Bradford e lidas com espectrofotômetro a 595nm. Os resultados mostraram que as proteínas se agrupam em categorias específicas, como as proteínas de choque térmico (HSPs), incluindo HSP40, HSP60, HSP70 e HSP90, e atuam em diversos compartimentos celulares. Foi observado que a variação de temperatura causou um impacto no perfil proteico das linhagens de S. cerevisiae industriais. As leveduras responderam de maneira distinta ao estresse térmico, apresentando produção máxima de proteínas após 24 horas de fermentação, exceto para a levedura Fleischmann, que apresentou menor acumulo de proteínas em 16 horas. A temperatura de 40ºC e o tempo prolongado de fermentação resultou em um perfil proteico reduzido. Esses resultados sugerem que a temperatura e o tempo prolongado de fermentação afetam os mecanismos de resposta molecular e o perfil proteico das leveduras.
Read moreSequencing Analysis of COI Genes Isolated from Vietnam’s Endemic Insect Species (Insecta: Plecoptera) for DNA Barcoding Database
The Insecta are the most diverse group of animals on the planet. The diversity of Plecoptera aquatic insect order is used as an environmental and ecological indicator. The study of endemic species is important for confirming the national biodiversity and contributing to the determination of national sovereignty. Despite Vietnam being a biodiversity hotspot, the number of known insect species remains limited. As a result, DNA barcoding has been used as a cutting-edge technique to efficiently and rapidly classify biological species. The Cytochrome c oxidase subunit I (COI) gene is widely regarded as a standard barcode for animal classification. In this study, we amplified and sequenced a portion of the COI gene fragment with a molecular weight of 710 bp for eight insect species belonging to the order Plecoptera, endemic to Vietnam. When compared to the previously published sequences of other Plecoptera species, the results of COI gene sequence analysis showed a high divergence of at least 9.9%. Molecular analysis of the studied species accurately demonstrated their endemism and morphological similarities. This study contributes to the development of a DNA barcoding database for endemic insects in Vietnam.
Read moreIncreasing the sensitivity, recovery, and integrality of spatially resolved proteomics by LCM-MTA
Abstract Conventional proteomic approaches neglect tissue heterogeneity and spatial localization information. Laser capture microdissection (LCM) can isolate specific cell populations or histological areas from heterogeneous tissue specimens while preserving spatial localization information. Formalin-fixed paraffin-embedded (FFPE) is currently a standardized method for long-term stable preservation of clinical tissue specimens. However, spatially resolved proteomics (SRP) studies of FFPE tissues by combined LCM and mass spectrometry (MS)-based proteomics face challenges, such as formalin-induced protein crosslinking limits protein extraction and digestion, protein loss during sample preparation, and the detectability of MS for trace tissues. Therefore, it is necessary to specifically develop SRP sample preparation methods and MS methods suitable for trace FFPE tissues. Here, we provide an SRP method suitable for trace FFPE tissues produced by LCM, termed LCM-Magnetic Trace Analysis (LCM-MTA), which can significantly increase the sensitivity, recovery, and integrality of SRP. The starting material has been reduced to about 15 cells, which resolution is comparable to existing spatially resolved transcriptome (SRT). We also apply our LCM-MTA into SRP studies on clinical colorectal cancer (CRC) tissues and accurately distinguish the functional differences of different cell types. In conclusion, LCM-MTA is a convenient, universal, and scalable method for SRP of trace FFPE tissues, which can be widely used in clinical and non-clinical research fields.
Read moreImproved yield of recombinant human IFN-α2b from mammalian cells using heterologous signal peptide approach
Dehydroamino acid chemical biology: an example of functional group interconversion on proteins
In nature, dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues are byproducts of protein aging, intermediates in the biosynthesis of lanthipeptides and products of bacterial phospholyases that inactivate host kinase immune responses. Recent chemical biology studies have demonstrated the possibility of mapping dehydroamino acids in complex proteomes in an unbiased manner that could further our understanding of the role of Dha and Dhb in biology and disease more broadly. From a synthetic perspective, chemical mutagenesis through site-selective formation of the unsaturated residue and subsequent addition chemistry has yielded homogeneous proteins bearing a variety of post-translational modifications (PTMs) which have assisted fundamental biological research. This Opinion discusses these recent advances and presents new opportunities for protein engineering and drug discovery.
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