Systems Biology

Members of the DIP and Dpr adhesion protein families use cis inhibition to shape neural development in Drosophila

Mon, 2025-03-03 06:00

PLoS Biol. 2025 Mar 3;23(3):e3003030. doi: 10.1371/journal.pbio.3003030. Online ahead of print.

ABSTRACT

In Drosophila, two interacting adhesion protein families, Defective proboscis responses (Dprs) and Dpr interacting proteins (DIPs), coordinate the assembly of neural networks. While intercellular DIP::Dpr interactions have been well characterized, DIPs and Dprs are often co-expressed within the same cells, raising the question as to whether they also interact in cis. We show, in cultured cells and in vivo, that DIP-α and DIP-δ can interact in cis with their ligands, Dpr6/10 and Dpr12, respectively. When co-expressed in cis with their cognate partners, these Dprs regulate the extent of trans binding, presumably through competitive cis interactions. We demonstrate the neurodevelopmental effects of cis inhibition in fly motor neurons and in the mushroom body. We further show that a long disordered region of DIP-α at the C-terminus is required for cis but not trans interactions, likely because it alleviates geometric constraints on cis binding. Thus, the balance between cis and trans interactions plays a role in controlling neural development.

PMID:40029885 | DOI:10.1371/journal.pbio.3003030

Categories: Literature Watch

A Systems Biology Approach of Quantifying Signal Transduction to B-Cell Proliferation and Differentiation

Mon, 2025-03-03 06:00

Methods Mol Biol. 2025;2909:165-178. doi: 10.1007/978-1-0716-4442-3_12.

ABSTRACT

Combining mathematical modeling with experiments enables quantitative understanding of cell signaling, transcriptional regulation, and cell fate decisions. Here, we provide a systems biology approach to link signal transduction with B cells fate decisions, to enable quantitative prediction of B-cell proliferation, and differentiation. We describe methodology to run simulations that reveal how signal transduction regulates gene expression and predicts cell fate decision. We describe how to quantitively validate modeling predictions with wet-lab experiments.

PMID:40029522 | DOI:10.1007/978-1-0716-4442-3_12

Categories: Literature Watch

Taxonomic description of <em>Micromonospora reichwaldensis</em> sp. nov. and its biosynthetic and plant growth-promoting potential

Mon, 2025-03-03 06:00

Microbiol Spectr. 2025 Mar 3:e0212924. doi: 10.1128/spectrum.02129-24. Online ahead of print.

ABSTRACT

Micromonospora strains proved to be a model organism for drug discovery and plant growth promotion (PGP). Strain DSM 115977 T was subjected to polyphasic taxonomic analysis and genome mining for biosynthetic gene clusters and PGP-associated genes in order to determine its taxonomic rank and assess its biosynthetic potential. The strain was found to form a novel species within the evolutionary radiation of the genus Micromonospora. The strain contained glucose, mannose, xylose, and ribose as whole-cell sugars and the isomer DL-diaminopimelic acid in its peptidoglycan. Strain DSM 115977T had iso-C15:0, iso-C16:0, C17:1cis 9, C17:0, iso-C17:0, and 10-methyl-C17:0 as fatty acid profile (>5%) and MK10-H4 and MK10-H6 as the predominant menaquinones (>10%). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, glycophospholipids, phosphoaminolipid, unidentified lipids, and phospholipids. The genome of the strain had a size of 7.0 Mbp with a DNA G + C content of 73.4%. It formed a well-supported sub-clade with its close phylogenomic neighbor, Micromonospora echinofusca DSM 43913T (98.7%). Digital DNA-DNA hybridization and average nucleotide identity derived from sequence comparisons between the strain and its close phylogenomic neighbors were below the thresholds of 70 and 95-96% for prokaryotic species demarcation, respectively. Based on these findings, strain DSM 115977T (Asg4T = KCTC 59188T) merits to be considered as the type strain of a new species for which the name Micromonospora reichwaldensis sp. nov. is proposed. Genome mining for biosynthetic gene clusters encoding specialized secondary metabolites highlighted its ability to produce potentially novel therapeutic compounds. The strain is rich in plant growth-promoting genes whose predicted products directly and indirectly affect the development and immune system of the plant.

IMPORTANCE: In view of the significant pharmaceutical, biotechnological, and ecological potentials of micromonosporae, it is particularly interesting to enhance the genetic diversity of this genus by focusing on the isolation of novel strain from underexplored habitats, with the promise that novel bacteria will lead to new chemical entities. In this report, modern polyphasic taxonomic study confirmed the assignment of strain DSM 115977T to a novel species for which the name Micromonospora reichwaldensis sp. nov. is proposed. The strain harbors in its genomic sequence several biosynthetic gene clusters for secondary metabolites and genes associated with plant growth-promoting features. The results of this study provide a very useful basis for launching more in-depth research into agriculture and/or drug discovery.

PMID:40029309 | DOI:10.1128/spectrum.02129-24

Categories: Literature Watch

Arabidopsis research in 2030: Translating the computable plant

Mon, 2025-03-03 06:00

Plant J. 2025 Mar;121(5):e70047. doi: 10.1111/tpj.70047.

ABSTRACT

Plants are essential for human survival. Over the past three decades, work with the reference plant Arabidopsis thaliana has significantly advanced plant biology research. One key event was the sequencing of its genome 25 years ago, which fostered many subsequent research technologies and datasets. Arabidopsis has been instrumental in elucidating plant-specific aspects of biology, developing research tools, and translating findings to crop improvement. It not only serves as a model for understanding plant biology and but also biology in other fields, with discoveries in Arabidopsis also having led to applications in human health, including insights into immunity, protein degradation, and circadian rhythms. Arabidopsis research has also fostered the development of tools useful for the wider biological research community, such as optogenetic systems and auxin-based degrons. This 4th Multinational Arabidopsis Steering Committee Roadmap outlines future directions, with emphasis on computational approaches, research support, translation to crops, conference accessibility, coordinated research efforts, climate change mitigation, sustainable production, and fundamental research. Arabidopsis will remain a nexus for discovery, innovation, and application, driving advances in both plant and human biology to the year 2030, and beyond.

PMID:40028766 | DOI:10.1111/tpj.70047

Categories: Literature Watch

A guide to selecting high-performing antibodies for CSNK1A1 (UniProt ID: P48729) for use in western blot, immunoprecipitation, and immunofluorescence

Mon, 2025-03-03 06:00

F1000Res. 2024 Sep 13;13:1055. doi: 10.12688/f1000research.155928.1. eCollection 2024.

ABSTRACT

CSNK1A1 is a key regulator of various signalling pathways, including the Wnt/β-catenin pathway. Playing a central role in cellular function and disease pathology, CSNK1A1 has emerged as an attractive protein target for therapeutic development. In this study we characterize ten CSNK1A1 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. This study is part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While the use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

PMID:40028451 | PMC:PMC11868743 | DOI:10.12688/f1000research.155928.1

Categories: Literature Watch

All-cause mortality according to COVID-19 vaccination status: An analysis of the UK office for National statistics public data

Mon, 2025-03-03 06:00

F1000Res. 2025 Feb 20;13:886. doi: 10.12688/f1000research.154058.2. eCollection 2024.

ABSTRACT

BACKGROUND: The mass vaccination campaign against COVID-19 has been commonly considered the best response to the global COVID-19 pandemic crisis. However, assessment of its real-world effect can be performed by analysis of all-cause mortality by vaccination status. The UK is perhaps the only country which has made publicly available all-cause mortality data by vaccination status.

METHODS: Data from April 2021 to May 2023 published by the UK Office for National Statistics (ONS) were retrospectively analyzed by age groups and vaccination status; the standardized mortality ratio (SMR) for all-cause and non-COVID-19 mortality was calculated against the corresponding unvaccinated groups.

RESULTS: We found that across all age groups, all-cause mortality SMRs increased from a certain date, dependent on the age group. Across all age groups, all-cause mortality SMRs were initially much lower than 1. However, due to their increase, by a certain date for the 18-39, 80-89 and 90+ age groups they exceeded the reference value. For the other age groups, the date at which the SMR would reach 1 can be predicted, provided the trend is maintained. Non-COVID-19 SMRs' trends were very similar. Their initial values much lower than 1 are suggestive of significant biases in the ONS dataset, leading to underestimate the risks for the vaccinated people, as it is implausible that COVID-19 vaccines protect against non-COVID-19 deaths.

CONCLUSIONS: The increase over time in all-cause death SMRs in vaccinated people compared to unvaccinated, and their excess from the reference values for certain age groups, should be carefully considered to understand the underlying factors. Furthermore, since the initial values of the SMRs are much lower than 1, we assume the presence of significant biases in the ONS dataset, leading to understimate the risks for the vaccinated people, as it is implausible that COVID-19 vaccines protect against non-COVID-19 deaths. It would be desirable for other major countries to systematically collect all-cause mortality by vaccination status and, in the meantime, a pending indepth investigations, much greater caution should be exercised in promoting mass vaccination campaigns.

PMID:40028449 | PMC:PMC11868741 | DOI:10.12688/f1000research.154058.2

Categories: Literature Watch

A design principle for neuronal firing with up-down oscillation through Na<sup>+</sup> dynamics

Mon, 2025-03-03 06:00

iScience. 2025 Jan 27;28(2):111904. doi: 10.1016/j.isci.2025.111904. eCollection 2025 Feb 21.

ABSTRACT

Nonrapid eye movement sleep is characterized by high-amplitude and low-frequency electroencephalography signals. These signals are thought to be produced by the synchronized activity of cortical neurons, demonstrating the alternating bursting (up) and resting (down) states. Here, such an activity is referred to as up-down oscillation (UDO). Previously, we discussed the importance of the Ca2+-dependent hyperpolarization pathway in the generation of UDO by simulating neuronal activity based on the Hodgkin-Huxley-type model. We herein focus on intracellular Na+ dynamics. The Na+-centered model indicates that the activation of voltage-gated Na+ channels leads to intracellular Na+ accumulation, which in turn activates Na+-dependent K+ (KNa) channels or Na+/K+ ATPases, resulting in the down state. Activation kinetics of voltage-gated Na+ channels are important in shaping the UDO firing. Therefore, our model demonstrates that voltage-gated Na+ and KNa channels or Na+/K+ ATPases are candidate pathways for UDO induction.

PMID:40028276 | PMC:PMC11869597 | DOI:10.1016/j.isci.2025.111904

Categories: Literature Watch

Long-Chain Cyclic Arylguanidines as Multifunctional Serotonin Receptor Ligands with Antiproliferative Activity

Mon, 2025-03-03 06:00

ACS Omega. 2025 Feb 11;10(7):6446-6469. doi: 10.1021/acsomega.4c06456. eCollection 2025 Feb 25.

ABSTRACT

Recent investigations have shown serotonin's stimulatory effect on several types of cancers and carcinoid tumors. Nowadays there has been a significant increase in interest in 5-HT7 and 5-HT5A receptors in the context of cancer treatment. The possible role of 5-HT6R in the pathogenesis and progression of glioma remains an interesting and relatively unexplored issue. We developed a new group of long-chain 2-aminoquinazoline sulfonamides as new multifunctional serotonin receptor ligands, focused on 5-HT6R. The chosen group was further evaluated for antiproliferative effects on 1321N1 astrocytoma cells, along with U87MG, U-251, and LN-229 glioblastoma cell lines. Certain compounds were subjected to in vitro absorption, distribution, metabolism, excretion, and toxicity (ADMET) testing, for assessing factors such as lipophilicity, plasma protein binding, phospholipid affinity, potential for drug-drug interactions (DDI), membrane permeability (PAMPA), metabolic stability, and hepatotoxicity. Additionally, in vivo testing was performed using the Danio rerio model. The developed group includes the selective 5-HT6R antagonist PP 15, dual ligand for 5-HT1AR/5-HT6R PP 13, and dual ligand for 5-HT5AR/5-HT6R PP 10. The use of multifunctional ligands was associated with high anticancer activity both against selected glioma cell lines and other cancers (IC50 < 25 μM).

PMID:40028084 | PMC:PMC11866022 | DOI:10.1021/acsomega.4c06456

Categories: Literature Watch

EGDB: A comprehensive multi-omics database for energy grasses and the epigenomic atlas of pearl millet

Mon, 2025-03-03 06:00

Imeta. 2024 Dec 28;4(1):e263. doi: 10.1002/imt2.263. eCollection 2025 Feb.

ABSTRACT

Given the key role of energy grasses in biomass energy, electricity, biofuels, and carbon sequestration, the Energy Grass Omics Database (EGDB) integrates germplasm data with genomics, transcriptomics, epigenomics, and phenomics data to support functional genomic research on diverse energy grass species. EGDB also currently supplies the largest epigenetic data set of energy grasses: a high-resolution chromatin modification, chromatin accessibility, and gene expression landscape of pearl millet to provide insights into regulatory traits essential for sustainable energy production.

PMID:40027491 | PMC:PMC11865331 | DOI:10.1002/imt2.263

Categories: Literature Watch

Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics

Mon, 2025-03-03 06:00

Imeta. 2025 Feb 21;4(1):e70000. doi: 10.1002/imt2.70000. eCollection 2025 Feb.

ABSTRACT

Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.

PMID:40027485 | PMC:PMC11865347 | DOI:10.1002/imt2.70000

Categories: Literature Watch

Proteomic Analysis of the Effects of Shenzhu Tiaopi Granules on Model Rats with Type 2 Diabetes Mellitus

Mon, 2025-03-03 06:00

Diabetes Metab Syndr Obes. 2025 Feb 25;18:583-599. doi: 10.2147/DMSO.S493036. eCollection 2025.

ABSTRACT

BACKGROUND: Shenzhu Tiaopi granule (STG) has antidiabetic functions. Data-independent acquisition proteomic technology is an integral part of systems biology. Herein, proteomics was used to analyse the effects of STG on type 2 diabetes mellitus (T2DM) and the mechanism by which STG normalizes glucose metabolism.

METHODS: Goto-Kakizaki (GK) T2DM model (Mod) rats, aged 15-16 weeks and with a fasting blood glucose (FBG) level of ≥11.1 mmol/L, were treated with metformin or STG for 12 weeks. Wistar rats aged 15-16 weeks were included in the control (Con) group. Body weight, FBG, total cholesterol (TC), total triglyceride (TG) levels and low-density lipoprotein (LDL-C) levels were measured, and pathological observation, Western blot analysis and data-independent acquisition proteomics of the liver were performed.

RESULTS: Significant differences in FBG, TC, TG, LDL-C (p < 0.01) and pathological liver morphology were observed between the Mod group and Con group, whereas both metformin and STG normalized the glucose and lipid metabolism indicators (p < 0.05 or p < 0.01). In total, 5856 proteins were identified via proteomic analysis, 97 of which were significantly differentially expressed in the liver and affected fatty acid metabolism, unsaturated fatty acid biosynthesis, the peroxisome proliferator-activated receptor (PPAR) signalling pathway, pyruvate metabolism, and terpenoid backbone biosynthesis. Screening identified 10 target proteins, including perilipin-2 (Plin2), pyruvate dehydrogenase kinase 4, farnesyl diphosphate synthase (Fdps) and farnesyl-diphosphate farnesyltransferase 1. Among these proteins, the key proteins were Plin2 and Fdps, which were found to be associated with the PPAR signalling pathway and terpenoid backbone biosynthesis via relationship networks. Plin2 and Fdps are closely related to hyperglycaemia. STG can downregulate Plin2 and upregulate Fdps (p < 0.01).

CONCLUSION: STG ameliorated hyperglycaemia by significantly altering the expression of different proteins, especially Fdps and Plin2, in the livers of GK rats. These findings may reveal the potential of traditional Chinese medicine for treating T2DM.

PMID:40026899 | PMC:PMC11871873 | DOI:10.2147/DMSO.S493036

Categories: Literature Watch

Mechanical strain focusing at topological defect sites in regenerating Hydra

Mon, 2025-03-03 06:00

Development. 2025 Feb 15;152(4):DEV204514. doi: 10.1242/dev.204514. Epub 2025 Mar 3.

ABSTRACT

The formation of a new head during Hydra regeneration involves the establishment of a head organizer that functions as a signaling center and contains an aster-shaped topological defect in the organization of the supracellular actomyosin fibers. Here, we show that the future head region in regenerating tissue fragments undergoes multiple instances of extensive stretching and rupture events from the onset of regeneration. These recurring localized tissue deformations arise due to transient contractions of the supracellular ectodermal actomyosin fibers that focus mechanical strain at defect sites. We further show that stabilization of aster-shaped defects is disrupted by perturbations of the Wnt signaling pathway. We propose a closed-loop feedback mechanism promoting head organizer formation, and develop a biophysical model of regenerating Hydra tissues that incorporates a morphogen source activated by mechanical strain and an alignment interaction directing fibers along morphogen gradients. We suggest that this positive-feedback loop leads to mechanical strain focusing at defect sites, enhancing local morphogen production and promoting robust organizer formation.

PMID:40026208 | DOI:10.1242/dev.204514

Categories: Literature Watch

Custom-Primed Rolling Circle Amplicons for Highly Accurate Nanopore Sequencing

Mon, 2025-03-03 06:00

Small Methods. 2025 Mar 3:e2401416. doi: 10.1002/smtd.202401416. Online ahead of print.

ABSTRACT

Tandem repeats of a certain DNA sequence can be generated using rolling circle amplification (RCA), where a circular template is continuously amplified by a polymerase with strand displacement activity. In leveraging the linear repetition of the target sequence, enhanced accuracy is achievable by consensus calling in nanopore sequencing. However, traditional multiply-primed RCA produces branched products with limited length, which may not be optimal for nanopore sequencing. In this study, an enhanced RCA protocol is introduced using sequence-specific primers to produce longer and less branched amplicons. Taking advantage of the RCA amplicons of tandem repeats, custom-primed rolling circle amplification sequencing (CPRSeq) is developed, a highly accurate nanopore sequencing pipeline. Utilizing CPRSeq, this successfully sequence standard samples of tumor-associated single nucleotide variants at low mutation frequency and accomplished the whole-genome sequencing and assembly of E. coli.

PMID:40025906 | DOI:10.1002/smtd.202401416

Categories: Literature Watch

GNINA 1.3: the next increment in molecular docking with deep learning

Sun, 2025-03-02 06:00

J Cheminform. 2025 Mar 2;17(1):28. doi: 10.1186/s13321-025-00973-x.

ABSTRACT

Computer-aided drug design has the potential to significantly reduce the astronomical costs of drug development, and molecular docking plays a prominent role in this process. Molecular docking is an in silico technique that predicts the bound 3D conformations of two molecules, a necessary step for other structure-based methods. Here, we describe version 1.3 of the open-source molecular docking software GNINA. This release updates the underlying deep learning framework to PyTorch, resulting in more computationally efficient docking and paving the way for seamless integration of other deep learning methods into the docking pipeline. We retrained our CNN scoring functions on the updated CrossDocked2020 v1.3 dataset and introduce knowledge-distilled CNN scoring functions to facilitate high-throughput virtual screening with GNINA. Furthermore, we add functionality for covalent docking, where an atom of the ligand is covalently bound to an atom of the receptor. This update expands the scope of docking with GNINA and further positions GNINA as a user-friendly, open-source molecular docking framework. GNINA is available at https://github.com/gnina/gnina .Scientific contributions: GNINA 1.3 is an open source a molecular docking tool with enhanced support for covalent docking and updated deep learning models for more effective docking and screening.

PMID:40025560 | DOI:10.1186/s13321-025-00973-x

Categories: Literature Watch

Rootrainertrons: a novel root phenotyping method used to identify genotypic variation in lettuce rooting

Sun, 2025-03-02 06:00

Plant Methods. 2025 Mar 2;21(1):29. doi: 10.1186/s13007-025-01348-x.

ABSTRACT

BACKGROUND: There is much interest in how roots can be manipulated to improve crop performance in a changing climate, yet root research is made difficult by the challenges of visualising the root system accurately, particularly when grown in natural environments such as soil. Scientists often resort to use of agar- or paper-based assays, which provide unnatural growing media, with the roots often exposed to light. Alternatives include rhizotrons or x-ray computed tomography, which require specialist and expensive pieces of equipment, not accessible to those in developing countries most affected by climate change. Another option is excavation of roots, however, this is time-consuming and near impossible to achieve without some degree of root damage. Therefore, new, affordable but reliable alternatives for root phenotyping are necessary.

RESULTS: This study reports a novel, low cost, Rootrainer-based system for root phenotyping. Rootrainers were tilted at an angle, in a rhizotron-like set-up. This encouraged root growth on the bottom plane of the Rootrainers, and since Rootrainers open (in a book-like fashion), root growth can be easily observed. This new technique was successfully used to uncover significant genotypic variance in rooting traits for a selection of lettuce (L. sativa) varieties across multiple timepoints.

CONCLUSION: This novel Rootrainertron method has many advantages over existing methods of phenotyping seedling roots. Rootrainers are cheap, and readily available from garden centres, unlike rhizotrons which are expensive and only available from specialist suppliers. Rootrainers allow the roots to grow in substrate medium, providing a significant advantage over agar and paper assays.This approach offers an affordable and relevant root phenotyping option and makes root phenotyping more accessible and applicable for researchers.

PMID:40025547 | DOI:10.1186/s13007-025-01348-x

Categories: Literature Watch

Blockade of the vaspin-AP-1 axis inhibits arthritis development

Sun, 2025-03-02 06:00

Exp Mol Med. 2025 Mar 3. doi: 10.1038/s12276-025-01418-z. Online ahead of print.

ABSTRACT

The trapping of pathogenic ligands can potentially be used to prevent signal transduction mediated by catabolic factor expression in osteoarthritis (OA). Although vaspin is known to function as a pathogenic ligand and represents a novel adipokine, little is known about its function and the impact of its nebulization-based administration in OA. Here we provide a report on the function of vaspin in articular chondrocytes and OA model mice. RNA sequencing analysis and ingenuity pathway analysis demonstrated that vaspin upregulation in chondrocytes triggers OA development-related signaling. Vaspin is upregulated in the injured cartilage of patients with OA and DMM (Destabilization of the Medial Meniscus) mice, and its overexpression induces catabolic factor expression in vitro under OA-mimicked conditions. Col2a1-vaspin Tg (Transgenic) animals showed extensive cartilage degradation, whereas vaspin-/- (knockout) mice exhibited decreased OA development. Furthermore, in silico and biochemical analyses showed that vaspin activates the p38 and JNK signaling pathways to regulate AP-1-driven catabolic factor production and cartilage breakdown. Finally, we identified and characterized a vaspin-targeting nanobody, vas nanobody, and showed that intraarticularly injected vas nanobody could effectively block the vaspin-AP-1 axis to treat OA in DMM mice. Together, our results suggest that blockade of the vaspin-AP-1 axis could be an effective therapeutic approach for preventing OA development.

PMID:40025171 | DOI:10.1038/s12276-025-01418-z

Categories: Literature Watch

A high throughput, high content screen for non-toxic small molecules that reduce levels of the nuclear lamina protein, Lamin B1

Sun, 2025-03-02 06:00

Sci Rep. 2025 Mar 1;15(1):7314. doi: 10.1038/s41598-025-91546-3.

ABSTRACT

Lamin B1 (LMNB1) is an intermediate filament protein that is an integral component of the nuclear lamina, a structure that is critical for nuclear organization and function. Mutations involving the lamin B1 gene cause the adult-onset demyelinating disorder, Autosomal Dominant Leukodystrophy (ADLD) which is charactered by increased lamin B1 expression. Increased LMNB1 expression is also associated with poorer outcomes in multiple cancer subtypes. Reducing LMNB1 is thus an attractive therapeutic pathway for ADLD and potentially other diseases. Here we present the results of a high throughput / high content screen (HTS/HCS) to identify small molecules that reduce LMNB1 levels. Approximately 97,000 molecules were screened using an inducible mouse fibroblast model of LMNB1 overexpression that we have previously generated. Two small molecules, Pubchem CID 662896 and CID 5308648, were identified that reduced LMNB1 in a dose dependent manner without causing cellular toxicity and corrected nuclear abnormalities associated with LMNB1 overexpression, a hallmark of ADLD. CID 662896 also reduced LMNB1 levels in ADLD patient fibroblast samples, exhibited favorable "drug-like" physicochemical properties and crossed the blood brain barrier in mouse studies. While CID 662896 may be a promising candidate for ADLD therapy, further investigations are required to determine its mechanism of action and ability to target disease relevant cell types.

PMID:40025114 | DOI:10.1038/s41598-025-91546-3

Categories: Literature Watch

Integrating DNA metabarcoding and morphological analysis improves marine zooplankton biodiversity assessment

Sun, 2025-03-02 06:00

Sci Rep. 2025 Mar 1;15(1):7283. doi: 10.1038/s41598-025-89684-9.

ABSTRACT

Marine copepod communities play crucial roles in ocean ecosystems. However, their accurate assessment remains challenging due to taxonomic complexities. This study combines morphological and DNA metabarcoding approaches to evaluate copepod diversity and community structure in the northern East China Sea. Zooplankton samples were collected from 10 stations along a coastal-offshore gradient in August 2019. Morphological analysis identified 34 species from 25 genera, while DNA metabarcoding detected 31 species from 20 genera. Both methods revealed distinct coastal and offshore assemblages, with Paracalanus parvus s.l. as the dominant species across all stations. A significant positive correlation was found between morphology-based individual counts and metabarcoding sequence reads (Spearman's Rho = 0.58, p < 0.001), improving at the genus level (Rho = 0.70, p < 0.001). Redundancy analysis revealed that salinity, temperature, and phytoplankton density significantly influenced copepod distribution. Although both approaches captured similar broad-scale patterns, they provided complementary insights into community structure. Morphological identification was more effective for detecting Cyclopoida diversity, whereas DNA metabarcoding had greater sensitivity for specific Calanoid species. This study underscores the value of integrating traditional and molecular methods for marine biodiversity assessment, especially in the context of global environmental changes.

PMID:40025088 | DOI:10.1038/s41598-025-89684-9

Categories: Literature Watch

Exploring biotechnology for plastic recycling, degradation and upcycling for a sustainable future

Sun, 2025-03-02 06:00

Biotechnol Adv. 2025 Feb 28:108544. doi: 10.1016/j.biotechadv.2025.108544. Online ahead of print.

ABSTRACT

The persistent demand for plastic commodities, inadequate recycling infrastructure, and pervasive environmental contamination due to plastic waste present a formidable global challenge. Recycling, degradation and upcycling are the three most important ways to solve the problem of plastic pollution. Sequential enzymatic and microbial degradation of mechanically and chemically pre-treated plastic waste can be orchestrated, followed by microbial conversion into value-added chemicals and polymers through mixed culture systems. Furthermore, plastics-degrading enzymes can be optimized through protein engineering to enhance their specific binding capacities, stability, and catalytic efficiency across a broad spectrum of polymer substrates under challenging high salinity and temperature conditions. Also, the production and formulation of enzyme mixtures can be fine-tuned to suit specific waste compositions, facilitating their effective deployment both in vitro, in vivo and in combination with chemical technologies. Here, we emphasized the comprehensive strategy leveraging microbial processes to transform mixed plastics of fossil-derived polymers such as PP, PE, PU, PET, and PS, most notably polyesters, in conjunction with potential biodegradable alternatives such as PLA and PHA. Any residual material resistant to enzymatic degradation can be reintroduced into the process loop following appropriate physicochemical treatment.

PMID:40024585 | DOI:10.1016/j.biotechadv.2025.108544

Categories: Literature Watch

PRAME expression in melanoma is negatively regulated by TET2-mediated DNA hydroxymethylation

Sun, 2025-03-02 06:00

Lab Invest. 2025 Feb 28:104123. doi: 10.1016/j.labinv.2025.104123. Online ahead of print.

ABSTRACT

Preferentially Expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared to nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis.

PMID:40024557 | DOI:10.1016/j.labinv.2025.104123

Categories: Literature Watch

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