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Proteolytic shedding of the prion protein:Uncovering“new”biological implications of a conserved cleavage event
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作者 Feizhi Song Valerija Kovac +4 位作者 Behnam Mohammadi Josephine E.Pippi Vladka Curin Serbec Markus Glatzel Hermann C.Altmeppen 《Neural Regeneration Research》 2026年第6期2329-2330,共2页
Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological... Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies). 展开更多
关键词 prion protein prp protein misfolding diseases prion protein neurodegenerative diseases read tools insights complex biological processes disease related roles physiological functions
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FROM MOLECULAR RESPONSE TO CELL RESPONSE-Approaching the complexity of biological systems
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作者 Wang Kui(The School of Pharmaceutical, Beijing Medical University) 《Bulletin of the Chinese Academy of Sciences》 2000年第1期17-25,共9页
I. THE COMPLEXITY OFBIOLOGICAL RESPONSESFor an organism, to be living or notdepends on its response to foreign matters.Facing the increasing amount and diversi-ty of chemicals, natural and synthetic, tounderstand the ... I. THE COMPLEXITY OFBIOLOGICAL RESPONSESFor an organism, to be living or notdepends on its response to foreign matters.Facing the increasing amount and diversi-ty of chemicals, natural and synthetic, tounderstand the principles of the biologicalresponses becomes extremely importantin pursuing the way of rational utiliza-tion and governing the foreign matters.However, most biological responses aretoo complex to explore their nature. Forinstance, the risk to human beings andorganisms related to the application ofrare earths in agriculture, forestation, fish-ery and husbandry has been argued 展开更多
关键词 FROM MOLECULAR RESPONSE TO CELL RESPONSE-Approaching the complexity of biological systems
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Paleoclimate Study of Mountain Ecosystems by Multiple Group Biological Analysis
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作者 Marina SKRYPNIKOVA Olga USPENSKAYA Olga KHOKHLOVA 《Journal of Mountain Science》 SCIE CSCD 2011年第1期24-36,共13页
Methodological problems of climatic reconstruction for different periods of Holocene are discussed on the basis of a multiple group biological analysis on peat-sapropel sediments. The possibility of biological analysi... Methodological problems of climatic reconstruction for different periods of Holocene are discussed on the basis of a multiple group biological analysis on peat-sapropel sediments. The possibility of biological analysis is exemplified by the paleoclimatic reconstruction for Carpathian and Altai Mountain ranges. For the "Skolevsky Beskidy" national park of Carpaty the paleoclimatic scenarios have been drown up aiming at the more precise definition of climatic conditions for the period of mass mountain slope terracing. The stability of terrace systems of various designs in the current climatic conditions has been assessed. It is shown that during periods of humid climate the terraces, whose designs have been focused on drainage, were built. In periods of dry and warm climate the terrace systems capable of accumulating water were built. Both these types of terrace systems are destroyed in nowadays. Only those terrace systems are stable which were adjusted by their builders to contrast variations of precipitation. For Western Altais the paleoclimatic scenario has been done to forecast the safety of the Bronze Age kurgans (burial earth mounds) with permafrost inside the construction. In the Altay region during the Holocene it has revealed two periods of sharp cooling, the peaks of which occurred in the intervals 4500- 4300 and 2500-2300 years pronounced climatic drying ago, and two periods of 4900-4700 and 130-70 years ago. Depletion of the algae composition in the layer corresponding to the last period of drying climate indicates a very sharp change in the parameters of moisture and turning the lake into a dry swamp. Periods of cold weather may have contributed to the formation of special ritual traditions of the Sakan tribes that require the frozen ground to bury the dead. The later climate fluctuations identified have not affected the safety of permafrost in burial mounds constructed in the V-III cc BC. 展开更多
关键词 Climatic reconstruction Complex group biological analysis of peat-sapropel sediments PALEOPEDOLOGY Soil evolution HOLOCENE
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Deciphering the blueprint of life:integrated protocols for single-cell multi-omics and functional genomics
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作者 Sha Hao Changya Chen 《Blood Science》 2026年第1期1-2,共2页
The rapid evolution of single-cell technologies has fundamentally transformed our ability to interrogate cellular heterogeneity and biological complexity with unprecedented resolution.Over the past few years,the field... The rapid evolution of single-cell technologies has fundamentally transformed our ability to interrogate cellular heterogeneity and biological complexity with unprecedented resolution.Over the past few years,the field has progressed beyond the creation of purely descriptive“cell atlases”toward a new frontier centered on functional validation and mechanistic dissection of regulatory landscapes.Among them,the launch and implementation of the Hematopoietic Ecosystem Multi-Omics Atlas of billions Blood Cells(HEMO ABC)Project is particularly significant.It aims to comprehensively and precisely characterize a vast number of blood cells,with the goal of constructing a massive database encompassing the characteristics and relationships of various cell types within the blood system.However,such an ambitious project faces numerous challenges.Data generated from different research platforms exhibit heterogeneity,making data integration a formidable task.Moreover,the absence of a unified and standardized technical system to ensure the quality and consistency of research.So this paradigm shift is particularly critical for the highly dynamic and complex hematopoietic ecosystem. 展开更多
关键词 mechanistic dissection regulatory landscapesamong multi omics hematopoietic ecosystem single cell technologies cellular heterogeneity functional genomics interrogate cellular heterogeneity biological complexity functional validation
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Multimorbidity and animal models
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作者 Xinpei Wang Yakun Ren +5 位作者 Xingjiu Yang Mengyuan Li Junxiu Liu Xiaoyan Du Wen Wang Ran Gao 《Animal Models and Experimental Medicine》 2025年第12期2196-2208,共13页
Multimorbidity—the co-occurrence of more than two chronic conditions in the same individual—is associated with premature death,diminished function,reduced quality of life,and increased societal burden.This complex s... Multimorbidity—the co-occurrence of more than two chronic conditions in the same individual—is associated with premature death,diminished function,reduced quality of life,and increased societal burden.This complex state involves dynamic interactions across multiple conditions,organ systems,and physiological pathways;yet research progress remains constrained by inadequate animal models that recapitulate human complexity.This review summarizes the predominant patterns of multimorbidity and evaluates current animal models spanning invertebrates,rodents,and large mammals.While no single model fully captures the multifaceted nature of human multimorbidity,we propose several strategic directions to address existing limitations:implementing a cross-species validation framework(from simple organisms to rodents to large mammals),standardizing protocols integrating multimodal risk factors,developing advanced non-animal models,and enhancing ethical oversight.Advancing multimorbidity models is crucial for decoding disease interactions and accelerating translation of research findings into improved patients outcomes. 展开更多
关键词 animal models biological complexity multimorbidity
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Facilitating single-cell chromatin accessibility research with a user-friendly database
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作者 Heyang HUA Sijie LI +1 位作者 Haitian LIANG Shengquan CHEN 《Frontiers of Computer Science》 2025年第11期163-164,共2页
1 Introduction Single-cell analyses have rapidly emerged as powerful tools for studying cellular heterogeneity,gene regulation,and complex biological processes[1].A key technology of singlecell analyses is single-cell... 1 Introduction Single-cell analyses have rapidly emerged as powerful tools for studying cellular heterogeneity,gene regulation,and complex biological processes[1].A key technology of singlecell analyses is single-cell chromatin accessibility sequencing(scCAS)which enables the analysis of chromatin accessibility at the resolution of individual cells[2],providing unprecedented insights into gene regulation,cellular differentiation,and disease mechanisms by profiling key regulatory regions such as transcription factor binding sites,enhancers,and promoters. 展开更多
关键词 ENHANCERS complex biological processes chromatin accessibility gene regulation single cell chromatin accessibility sequencing transcription factor binding sites promoters analysis chromatin accessibility
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Intelligent single-cell manipulation:LLMs-and object detection-enhanced active-matrix digital microfluidics
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作者 Zhiqiang Jia Chen Jiang +9 位作者 Jiahao Li Yacine Belgaid Mingfeng Ge Li Li Siyi Hu Xing Huang Tsung-Yi Ho Wenfei Dong Zhiwen Yu Hanbin Ma 《Microsystems & Nanoengineering》 2025年第4期97-111,共15页
Single-cell analysis is crucial for deciphering cellular heterogeneity and understanding complex biological systems.However,most existing single-cell sample manipulation(SCSM)systems suffer from various drawbacks such... Single-cell analysis is crucial for deciphering cellular heterogeneity and understanding complex biological systems.However,most existing single-cell sample manipulation(SCSM)systems suffer from various drawbacks such as high cost,low throughput,and heavy reliance on human interventions.Currently,large language models(LLMs)have been used in robotic platforms,but a limited number of studies have reported the application of LLMs in the field of lab-ona-chip automation.Consequently,we have developed an active-matrix digital microfluidic(AM-DMF)platform that realizes fully automated biological procedures for intelligent SCSM.By combining this with a fully programmable labon-a-chip system,we present a breakthrough for SCSM by combining LLMs and object detection technologies.With the proposed platform,the single-cell sample generation rate and identification precision reach up to 25%and 98%,respectively,which are much higher than the existing platforms in terms of SCSM efficiency and performance.Furthermore,a three-class detection method considering droplet edges is implemented to realize the automatic identification of cells and oil bubbles.This method achieves a 1.0%improvement in cell recognition accuracy according to the AP_(75)^(test)metric,while efficiently distinguishing obscured cells at droplet edges,where approximately 20%of all droplets contain cells at their edges.More importantly,as the first attempt,a ubiquitous tool for automatic SCSM workflow generation is developed based on the LLMs,thus advancing the development and progression of the field of single-cell analysis in the life sciences. 展开更多
关键词 deciphering cellular heterogeneity large language models understanding complex biological systemshowevermost language models llms intelligent single cell manipulation active matrix digital microfluidics single cell analysis object detection
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Three-color single-molecule localization microscopy in chromatin
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作者 Nicolas Acosta Ruyi Gong +7 位作者 Yuanzhe Su Jane Frederick Karla I.Medina Wing Shun Li Kiana Mohammadian Luay Almassalha Geng Wang Vadim Backman 《Light: Science & Applications》 2025年第5期1265-1277,共13页
Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets... Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin.Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales,from nanometers to micrometers.Single molecule localization microscopy(SMLM)methods,such as STORM,are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.Multi-label imaging of chromatin is necessary to unpack its structural complexity.However,these efforts are challenged by the high-density nuclear environment,which can affect antibody binding affinities,diffusivity and non-specific interactions.Optimizing buffer conditions,fluorophore stability,and antibody specificity is crucial for achieving effective antibody conjugates.Here,we demonstrate a sequential immunolabeling protocol that reliably enables three-color studies within the dense nuclear environment.This protocol couples multiplexed localization datasets with a robust analysis algorithm,which utilizes localizations from one target as seed points for distance,density and multi-label joint affinity measurements to explore complex organization of all three targets.Applying this multiplexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories,but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters.This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy. 展开更多
关键词 investigating complex biological targets hierarchical organization molecule localization microscopy smlm methodssuch three color single molecule localization microscopy visualize structures chromatin super resolution microscopy conventional optical microscopy structural compartments
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SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM 被引量:4
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作者 LIHong ZHOUZhiyuan DAIRongyang LUOBo ZHENGXiaoli YANGWenli HETao WUMinglu 《Journal of Systems Science & Complexity》 SCIE EI CSCD 2004年第3期349-368,共20页
In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to th... In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems. 展开更多
关键词 biological complexity self-adaptive system EMERGENCY computer simulation cellular signaling transduction
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Modeling the antigen recognition by B-cell and T-cell receptors through thermostatted kinetic theory methods
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作者 Carlo Bianca Louis Brezin 《International Journal of Biomathematics》 2017年第5期263-299,共37页
The activation and the resulting response of the immune system to antigens comprise different complex processes and cells. This paper aims at modeling the processes of recognition and learning of the immune system by ... The activation and the resulting response of the immune system to antigens comprise different complex processes and cells. This paper aims at modeling the processes of recognition and learning of the immune system by means of the thermostatted kinetic theory methods. Specifically, the thermostatted kinetic framework is firstly generalized for taking into account that in some processes of proliferation of the cells, the rate is also function of the degree of information exchanged amongst cells. In particular, within the new framework, a mathematical model is proposed for miming the recognition process of the immune system through the definition of interactions between the cytoto^ic and humoral components of the adaptive immune system via T- and B-cells. The model validation is obtained by performing a sensitivity analysis on the parameters which depicts the main emerging phenomena and the different phases of the recognition and learning of the immune system. 展开更多
关键词 Thermostatted kinetic theory integro-differential models learning and memory biological complexity immune system.
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From sequence to mechanobiology?Promises and challenges for AlphaFold 3 被引量:1
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作者 Francesco Zonta Sergio Pantano 《Mechanobiology in Medicine》 2024年第3期1-3,共3页
Interactions between macromolecules orchestrate many mechanobiology processes.However,progress in the field has often been hindered by the monetary and time costs of obtaining reliable experimental structures.In recen... Interactions between macromolecules orchestrate many mechanobiology processes.However,progress in the field has often been hindered by the monetary and time costs of obtaining reliable experimental structures.In recent years,deep-learning methods,such as AlphaFold,have democratized access to high-quality predictions of the structural properties of proteins and other macromolecules.The newest implementation,AlphaFold 3,significantly expands the applications of its predecessor,AlphaFold 2,by incorporating reliable models for small molecules and nucleic acids and enhancing the prediction of macromolecular complexes.While several limitations still exist,the continuous improvement of machine learning methods like AlphaFold is producing a significant revolution in the field.The possibility of easily accessing structural predictions of biomolecular complexes may create substantial impacts in mechanobiology.Indeed,structural studies are at the basis of several applications in the field,such as drug discovery for mechanosensing proteins,development of mechanotherapy,understanding the mechanotransduction mechanisms and the mechanistic basis of diseases,or designing biomaterials for tissue engineering. 展开更多
关键词 AlphaFold Protein folding biological complexes Structure predictions Drug design
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The Next Frontier:Micro/Nanorobots Operating Inside the Living Body
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作者 Ningbo Yu Jie Yang +3 位作者 Zicheng Ni Yuepeng Cai Beatriz Jurado-Sánchez Renfeng Dong 《SmartBot》 2026年第1期87-108,共22页
Biomedical micro/nanorobots(MNRs)have emerged as a cutting-edge research field,offering novel strategies for precise in vivo manipulation and targeted therapeutic delivery.By harnessing external energy sources,such as... Biomedical micro/nanorobots(MNRs)have emerged as a cutting-edge research field,offering novel strategies for precise in vivo manipulation and targeted therapeutic delivery.By harnessing external energy sources,such as chemical fuels,magnetic fields,light,acoustic waves,and biohybrid designs,these miniature intelligent systems achieve efficient autonomous navigation through complex biological environments while overcoming the physical limitations of conventional medical technologies.Current research focuses on material innovation,motion control,biocompatibility,and functional integration.These efforts have led to advances in disease treatment,barrier penetration,diagnostic imaging,wound healing,and minimally invasive procedures.However,clinical translation remains hindered by critical hurdles such as long-term biosafety,stable energy supply,high-resolution real-time tracking,and scalable manufacturing.This review systematically summarizes recent advancements in MNR research,with a particular emphasis on material-level innovations in both artificially synthesized and naturally derived systems.It provides an in-depth analysis of their unique capabilities in overcoming biological barriers and performing precise tasks in vivo.Furthermore,the review highlights pioneering diagnostic-therapeutic integration and outlines forward-looking strategies to accelerate clinical adoption.Specifically,we contend that future progress must converge advances in smart responsive materials,multiphysics cooperative actuation,and artificial intelligence-assisted guidance systems to overcome existing limitations in microscale in vivo operation.By offering a synthesized perspective and a clear roadmap,this review aims to steer next-generation MNR research toward practical applications in personalized medicine,regenerative therapies,and intelligent theranostics,thereby fostering a paradigm shift in biomedical technology. 展开更多
关键词 targeted therapeutic deliveryby overcoming physical limitations miniature intelligent systems conventional medical technologiescurrent biohybrid designsthese autonomous navigation complex biological environments precise vivo manipulation energy sourcessuch
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