Macromolecular condensation buffers intracellular water potential

Nature, Год журнала: 2023, Номер 623(7988), С. 842 - 852

Опубликована: Окт. 18, 2023

Abstract Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive folding macromolecular interactions 1 . Reciprocally, macromolecules restrict the movement of ‘structured’ molecules within their hydration layers, reducing available ‘free’ bulk therefore total thermodynamic potential energy water, or potential. Here, concentrated solutions such as cytosol, we found that modest changes in temperature greatly affect potential, are counteracted by opposing osmotic strength. This duality strength enables simple manipulations to prevent cell death after extreme cold heat shock. Physiologically, cells must sustain against fluctuating temperature, pressure strength, which impact seconds. Yet, established mechanisms homeostasis act over much slower timescales 2,3 ; postulated existence a rapid compensatory response. We find this is performed potential-driven assembly, particularly biomolecular condensation intrinsically disordered proteins. The formation dissolution condensates liberates captures free respectively, quickly counteracting thermal perturbations consequently robustly buffered cytoplasm. Our results indicate constitutes an intrinsic biophysical feedback response rapidly compensates for intracellular fluctuations. suggest preserving cytosol overlooked evolutionary driver (dis)order function.

Язык: Английский

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Lanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 15, 2024

Abstract Nanothermometers enable the detection of temperature changes at microscopic scale, which is crucial for elucidating biological mechanisms and guiding treatment strategies. However, monitoring micron-scale structures in vivo using luminescent nanothermometers remains challenging, primarily due to severe scattering effect tissue that compromises imaging resolution. Herein, a lanthanide luminescence nanothermometer with working wavelength beyond 1500 nm developed achieve high-resolution vivo. The energy transfer between ions (Er 3+ Yb ) H 2 O molecules, called environment quenching assisted downshifting process, utilized establish temperature-sensitive emissions 1550 980 nm. Using an optimized thin active shell doped ions, nanothermometer’s thermal sensitivity emission intensity are enhanced by modulating process. Consequently, minimally invasive cerebrovascular system mice resolution nearly 200 μm achieved nanothermometer. This work points method micron-level vivo, potentially giving insights into research sensing, disease diagnosis, development.

Язык: Английский

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Cytosolic Hsp90 Isoform-Specific Functions and Clinical Significance

Biomolecules, Год журнала: 2022, Номер 12(9), С. 1166 - 1166

Опубликована: Авг. 23, 2022

The heat shock protein 90 (Hsp90) is a molecular chaperone and key regulator of proteostasis under both physiological stress conditions. In mammals, there are two cytosolic Hsp90 isoforms: Hsp90α Hsp90β. These isoforms 85% identical encoded by different genes. Hsp90β constitutively expressed essential for early mouse development, while stress-inducible not necessary survivability. known to have largely overlapping functions interact with large fraction the proteome. To what extent isoform-specific at level has only relatively recently begun emerge. There studies indicating that one isoform more involved in functionality specific tissue or cell type. Moreover, many diseases, functionally altered cells appear be dependent on particular isoform. This leaves space designing therapeutic strategies an way, which may overcome unfavorable outcome pan-Hsp90 inhibition encountered previous clinical trials. For this succeed, must understood detail. review, we summarize available information mammalian connect it possible applications.

Язык: Английский

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Implication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 9, 2024

Abstract Neuronal differentiation—the development of neurons from neural stem cells—involves neurite outgrowth and is a key process during the regeneration functions. In addition to various chemical signaling mechanisms, it has been suggested that thermal stimuli induce neuronal differentiation. However, function physiological subcellular thermogenesis differentiation remains unknown. Here we create methods manipulate observe local intracellular temperature, investigate effects noninvasive temperature changes on using neuron-like PC12 cells. Using quantitative heating with an infrared laser, find increase in (especially nucleus) facilitates outgrowth. Intracellular thermometry reveals accompanied by associated transcription translation. Suppression inhibits Furthermore, spontaneous elevation involved primary mouse cortical neurons. These results offer model for understanding induced signaling.

Язык: Английский

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BioClocks UK: driving robust cycles of discovery to impact

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2025, Номер 380(1918)

Опубликована: Янв. 23, 2025

Chronobiology is a multidisciplinary field that extends across the tree of life, transcends all scales biological organization, and has huge translational potential. For UK to harness opportunities presented within applied chronobiology, we need build our network outwards reach stakeholders can directly benefit from discoveries. In this article, discuss importance rhythms health, society, economy environment, with particular focus on circadian rhythms. We subsequently introduce vision objectives BioClocks UK, newly formed research network, whose mission stimulate researcher interactions sustain discovery-impact cycles between chronobiologists, wider communities multiple industry sectors. This article part Theo Murphy meeting issue ‘Circadian in infection immunity’.

Язык: Английский

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PERspectives on circadian cell biology

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2025, Номер 380(1918)

Опубликована: Янв. 23, 2025

Daily rhythms in the activities of PERIOD proteins are critical to temporal regulation mammalian physiology. While molecular partners and genetic circuits that allow effect auto-repression regulate transcriptional programmes increasingly well understood, comprehension time-resolved mechanisms conduct this daily dance is incomplete. Here, we consider character controversies central clock protein with a focus on its intrinsically disordered nature. This article part Theo Murphy meeting issue ‘Circadian infection immunity’.

Язык: Английский

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Artificial intelligence-based prediction of oral mucositis in patients with head-and-neck cancer: A prospective observational study utilizing a thermographic approach

Cancer Research Statistics and Treatment, Год журнала: 2023, Номер 6(2), С. 181 - 190

Опубликована: Апрель 1, 2023

ABSTRACT JOURNAL/crsat/04.03/02201859-202306020-00003/figure1/v/2023-08-03T140821Z/r/image-tiff JOURNAL/crsat/04.03/02201859-202306020-00003/figure2/v/2023-08-03T140821Z/r/image-tiff Background: In patients with locally advanced head-and-neck squamous cell carcinoma (HNSCC), chemoradiotherapy improves outcomes. Radiotherapy commonly causes mucositis, which can significantly impede treatment and reduce the patient’s quality of life. Patients severe mucocutaneous toxicity will show significant changes in thermal intensity early on, when compared to identically treated counterparts without toxicity. Objective: We aimed assess accuracy automated computer-aided deep learning approach predicting occurrence oral mucositis HNSCC undergoing radiotherapy alone or concurrent chemotherapy. Materials Methods: This prospective observational study was conducted over four weeks September 2021 Department at Homi Bhabha Cancer Hospital, Sangrur (Punjab, India). enrolled who were planned for radical intent radiotherapy, Using an technique, we analyzed images taken a FLIR-E60 camera on same day that received Thermal binarily classified into two grades, is, Grade 0 (absence mucositis) I (asymptomatic mild symptoms mucositis). The dataset split training testing cohorts, ratio 0.8. Accuracy calculated as correct predicted instances total number dataset. categorized accuracy. Results: A 386 from 50 acquired. Of these, 308 (79.8%) used set 78 (20.2%) set. There 206 (53.4%) 180 (46.6%) I. difference profile images; P = 0.01. model achieved promising results 100% 82% led improvement false-negative rate proposed model, indicating improved performance. Conclusion: approach-based analysis be useful technique stage treatment, thus helping intensifying supportive care. has been tested diverse dataset, its performance terms validates model.

Язык: Английский

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Bright and Photostable TADF‐Emitting Zirconium(IV) Pyridinedipyrrolide Complexes: Efficient Dyes for Decay Time‐Based Temperature Sensing and Imaging

Advanced Optical Materials, Год журнала: 2023, Номер 11(9)

Опубликована: Фев. 19, 2023

Abstract Luminescence thermometry represents a technique of choice for measurements in small objects and imaging temperature distribution. However, most state‐of‐the‐art luminescent probes are limited spectral characteristics, brightness, photostability, sensitivity. Molecular thermometers the new generation utilizing air moisture‐stable zirconium(IV) pyridinedipyrrolide complexes can address all these limitations. The dyes emit pure thermally activated delayed fluorescence without any prompt show unique combination attractive features: a) visible light excitation emission orange/red region, b) high luminescence brightness (quantum yields ≈0.5 toluene 0.8–1.0 polystyrene matrix), c) excellent d) suitability two‐photon e) mono‐exponential decay on order tens to hundreds microseconds with strongly temperature‐dependent lifetimes (between −2.5 −2.9% K −1 at 25 °C). Immobilization gas‐blocking polymers sensing materials self‐referenced time read‐out that manufactured two common formats: planar optodes water‐dispersible nanoparticles. Positively charged nanoparticles demonstrated be suitable nanothermometry live cells multicellular spheroids. Negatively represent advanced analytical tools gradients samples volumes such as microfluidic devices.

Язык: Английский

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Probing organoid metabolism using fluorescence lifetime imaging microscopy (FLIM): The next frontier of drug discovery and disease understanding

Advanced Drug Delivery Reviews, Год журнала: 2023, Номер 201, С. 115081 - 115081

Опубликована: Авг. 28, 2023

Язык: Английский

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Stroke in the Time of Circadian Medicine

Circulation Research, Год журнала: 2024, Номер 134(6), С. 770 - 790

Опубликована: Март 14, 2024

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also important determinants clinical outcome. In this review, we provide a comprehensive overview interplay between chronobiology cerebrovascular disease. We discuss regulation pathophysiological mechanisms underlying onset or tolerance as well in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, inflammation/immunity. Furthermore, present evidence supporting link disrupted rhythms increased susceptibility to propose that biochemical physiological pathways brain increase damage after sleep attenuate treatment effectiveness during active phase. review underscores importance considering biology understanding pathology choice dementia speculates patient's chronotype may be an factor developing precision following

Язык: Английский

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