318 research outputs found

    The impact and applications of ChatGPT: a systematic review of literature reviews

    Full text link
    The conversational artificial-intelligence (AI) technology ChatGPT has become one of the most widely used natural language processing tools. With thousands of published papers demonstrating its applications across various industries and fields, ChatGPT has sparked significant interest in the research community. Reviews of primary data have also begun to emerge. An overview of the available evidence from multiple reviews and studies could provide further insights, minimize redundancy, and identify areas where further research is needed. Objective: To evaluate the existing reviews and literature related to ChatGPT's applications and its potential impact on different fields by conducting a systematic review of reviews and bibliometric analysis of primary literature. Methods: PubMed, EuropePMC, Dimensions AI, medRxiv, bioRxiv, arXiv, and Google Scholar were searched for ChatGPT-related publications from 2022 to 4/30/2023. Studies including secondary data related to the application of ChatGPT were considered. Reporting and risk of bias assesment was performed using PRISMA guidelines. Results: A total of 305 unique records with potential relevance to the review were identified from a pool of over 2,000 original articles. After multi-step screening process, 11 reviews were selected, consisting of 9 reviews specifically focused on ChatGPT and 2 reviews on broader AI topics that also included discussions on ChatGPT. We also conducted bibliometric analysis of primary data. Conclusions: While AI has the potential to revolutionize various industries, further interdisciplinary research, customized integrations, and ethical innovation are necessary to address existing concerns and ensure its responsible use. Protocol Registration: PROSPERO registration no. CRD42023417336, DOI 10.17605/OSF.IO/87U6Q

    Real-time observations of single bacteriophage λ DNA ejections in vitro

    Get PDF
    The physical, chemical, and structural features of bacteriophage genome release have been the subject of much recent attention. Many theoretical and experimental studies have centered on the internal forces driving the ejection process. Recently, Mangenot et al. [Mangenot S, Hochrein M, Rädler J, Letellier L (2005) Curr Biol 15:430–435.] reported fluorescence microscopy of phage T5 ejections, which proceeded stepwise between DNA nicks, reaching a translocation speed of 75 kbp/s or higher. It is still unknown how high the speed actually is. This paper reports real-time measurements of ejection from phage {lambda}, revealing how the speed depends on key physical parameters such as genome length and ionic state of the buffer. Except for a pause before DNA is finally released, the entire 48.5-kbp genome is translocated in {approx}1.5 s without interruption, reaching a speed of 60 kbp/s. The process gives insights particularly into the effects of two parameters: a shorter genome length results in lower speed but a shorter total time, and the presence of divalent magnesium ions (replacing sodium) reduces the pressure, increasing ejection time to 8–11 s. Pressure caused by DNA–DNA interactions within the head affects the initiation of ejection, but the close packing is also the dominant source of friction: more tightly packed phages initiate ejection earlier, but with a lower initial speed. The details of ejection revealed in this study are probably generic features of DNA translocation in bacteriophages and have implications for the dynamics of DNA in other biological systems

    Dynamics of DNA Ejection From Bacteriophage

    Get PDF
    The ejection of DNA from a bacterial virus (``phage'') into its host cell is a biologically important example of the translocation of a macromolecular chain along its length through a membrane. The simplest mechanism for this motion is diffusion, but in the case of phage ejection a significant driving force derives from the high degree of stress to which the DNA is subjected in the viral capsid. The translocation is further sped up by the ratcheting and entropic forces associated with proteins that bind to the viral DNA in the host cell cytoplasm. We formulate a generalized diffusion equation that includes these various pushing and pulling effects and make estimates of the corresponding speed-ups in the overall translocation process. Stress in the capsid is the dominant factor throughout early ejection, with the pull due to binding particles taking over at later stages. Confinement effects are also investigated, in the case where the phage injects its DNA into a volume comparable to the capsid size. Our results suggest a series of in vitro experiments involving the ejection of DNA into vesicles filled with varying amounts of binding proteins from phage whose state of stress is controlled by ambient salt conditions or by tuning genome length.Comment: 17 pages, 5 figure

    Forces During Bacteriophage DNA Packaging and Ejection

    Get PDF
    The conjunction of insights from structural biology, solution biochemistry, genetics and single molecule biophysics has provided a renewed impetus for the construction of quantitative models of biological processes. One area that has been a beneficiary of these experimental techniques is the study of viruses. In this paper we describe how the insights obtained from such experiments can be utilized to construct physical models of processes in the viral life cycle. We focus on dsDNA bacteriophages and show that the bending elasticity of DNA and its electrostatics in solution can be combined to determine the forces experienced during packaging and ejection of the viral genome. Furthermore, we quantitatively analyze the effect of fluid viscosity and capsid expansion on the forces experienced during packaging. Finally, we present a model for DNA ejection from bacteriophages based on the hypothesis that the energy stored in the tightly packed genome within the capsid leads to its forceful ejection. The predictions of our model can be tested through experiments in vitro where DNA ejection is inhibited by the application of external osmotic pressure

    Изучение антифибротических свойств препарата пирфенидон на клеточной культуре фибробластов слизистой оболочки полости носа

    Get PDF
    Background: One of the main reasons of failure in surgical treatment of primary acquired nasolacrimal duct obstruction is excessive postoperative scarring of the dacryostomy. Despite the variety of procedures designed to prevent this, conflicting evidence of their efficacy and safety provide incentive for further research of antifibrotic therapeutics for adjunctive use in dacryocystorhinostomy.Aims: To evaluate the antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture.Materials and methods: Human nasal mucosal fibroblast cell cultures were established using samples obtained from 3 consecutive patients undergoing endonasal endoscopic dacryocystorhinostomy. Cell viability following treatment with pirfenidone was evaluated using MTS-assay. Induced inhibition of cell proliferation and migration was determined using scratch wound assay.Results: In this study pirfenidone exhibited a significant dose-dependent inhibiting effect on fibroblast proliferation with insignificant cell toxicity. Cell viability following 48 hours of incubation with various pirfenidone concentrations did not drop below 80%. The recovery of the fibroblast monolayer assessed after 24 hours of incubation was 84.88 and 8.26% in the control group, at a drug concentration of 0.15 mg/ml. Cell proliferation and migration was severely inhibited in cell culture specimens treated with pirfenidone compared to controls. The difference between groups was statistically significant (p=0,001).Conclusions: In our study pirfenidone demonstrated a pronounced antifibrotic effect. It is unlikely that inhibition of proliferation and migration of human nasal mucosal fibroblasts is mediated by cell toxicity of this medication as it was evaluated as low. Nonetheless an in vitro analysis is insufficient to judge pirfenidone’s efficacy and safety in preventing cicatrix formation following dacrycystorhinostomy. Обоснование. Одной из основных причин неудачи в хирургическом лечении дакриоцистита является рубцовое заращение дакриостомы ― соустья между слезным мешком и полостью носа. Несмотря на наличие большого количества предложенныхсредств и методик профилактики этого явления, литературные данные свидетельствуют об отсутствии надежных методов, позволяющих предотвратить рубцевание дакриостомы в послеоперационном периоде, что обусловливает необходимость продолжения исследований в данном направлении. Цель исследования ― изучение антифибротических свойств препарата пирфенидон на клеточной культуре фибробластов слизистой оболочки полости носа. Методы. Клетки для культуры фибробластов слизистой оболочки полости носа были получены у 3 пациентов во времяэндоназальной эндоскопической дакриоцисториностомии. Токсичность препарата вконцентрациях от 0,01 до 0,5 мг/мл была исследована при помощи теста с MTS-реагентом. Ингибирующий эффект пирфенидона на миграцию фибробластов оценивали на основе модели раны монослоя для концентраций 0,15 и 0,3 мг/мл. Результаты. Внастоящем исследовании пирфенидон оказывал выраженный дозозависимый эффект на миграцию фибробластов без выраженной цитотоксичности. По данным MTS- теста, количество жизнеспособных клеток после 48 ч инкубации с различными концентрациями препарата не опускалась ниже 80%. В контрольной группе после 24 ч инкубации восстановление клеточного монослоя произошло практически полностью (на 84,88±4,80%). В опытных лунках, в которые был добавлен препарат, монослой практически не восстановился. Рост монослоя в группах с добавлением 0,15 мг/мл препарата составил 8,26± 6,09%. При концентрации препарата 0,3 мг/мл произошло увеличение ширины поврежденного участка на 2,10%. Различия между группами были статистически достоверными (p=0,001).Заключение. Результаты настоящегоисследования свидетельствуют о высокой антифибротической эффективности препарата пирфенидон, не связанной с цитотоксическим эффектом. Тем не менее, несмотря на невысокую токсичность препарата, по данным этого и других исследований in vitro, вывод о целесообразности и безопасности применения препарата в профилактике заращения соустья после дакриоцисториностомии возможно сделать только на основании исследования in vivo

    Collective Dynamics of the Ribosomal Tunnel Revealed by Elastic Network Modeling

    Get PDF
    The collective dynamics of the nascent polypeptide exit tunnel are investigated with the computationally efficient elastic network model using normal mode analysis. The calculated normal modes are considered individually and in linear combinations with different coefficients mimicking the phase angles between modes, in order to follow the mechanistic motions of tunnel wall residues. The low frequency fluctuations indicate three distinct regions along the tunnel - the entrance, the neck and the exit – each having distinctly different domain motions. Generally the lining of the entrance region moves in the exit direction, with the exit region having significantly larger motions, but in a perpendicular direction, whereas the confined neck region generally has rotational motions. Especially the universally conserved extensions of ribosomal proteins L4 and L22 located at the narrowest and mechanistically strategic region of tunnel undergo generally anti- or non-correlated motions, which may have an important role in nascent polypeptide gating mechanism. These motions appear to be sufficiently robust so as to be unaffected by the presence of a peptide chain in the tunnel

    Protein folding on the ribosome studied using NMR spectroscopy

    Get PDF
    NMR spectroscopy is a powerful tool for the investigation of protein folding and misfolding, providing a characterization of molecular structure, dynamics and exchange processes, across a very wide range of timescales and with near atomic resolution. In recent years NMR methods have also been developed to study protein folding as it might occur within the cell, in a de novo manner, by observing the folding of nascent polypeptides in the process of emerging from the ribosome during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient local flexibility that sharp resonances may be observed in solution-state NMR spectra. In providing information on dynamic regions of the structure, NMR spectroscopy is therefore highly complementary to alternative methods such as X-ray crystallography and cryo-electron microscopy, which have successfully characterized the rigid core of the ribosome particle. However, the low working concentrations and limited sample stability associated with ribosome-nascent chain complexes means that such studies still present significant technical challenges to the NMR spectroscopist. This review will discuss the progress that has been made in this area, surveying all NMR studies that have been published to date, and with a particular focus on strategies for improving experimental sensitivity

    Ганглиозные клетки сетчатки: возможности нейропротекции при глаукоме

    Get PDF
    Neuroprotective therapy is a contemporary and promising direction in glaucoma treatment. This strategy involves retinal protection, as well as the protection of optic nerve fibers from damaging by various factors. Cell therapy is gradually finding its practical application in almost all areas of clinical medicine, including ophthalmology. The positive effect of cell transplantation is associated with several mechanisms, including the trophic one and therefore, retinal cells metabolic stress correction is an important aspect of neuroprotection in glaucoma.The review analyzes the current state of researching retinal ganglion cells as targets for glaucoma therapy and gives a general idea about the new approaches to the treatment of this disease with the use of cell technologies based on neuroprotection strategies. Нейропротекторная терапия является современным и одним из наиболее перспективных направлений в лечении глаукомы. Эта стратегия подразумевает защиту сетчатки, а также волокон зрительного нерва от повреждающего действия различных факторов. Клеточная терапия постепенно находит практическое применение почти во всех областях клинической медицины, в том числе и в офтальмологии. Считается, что положительное влияние трансплантации клеток обусловлено нескольки- ми механизмами, одним из которых является трофический, поэтому одним из важных аспектов нейропротекции при глаукоме является коррекция метаболического стресса клеток сетчатки.В обзоре анализируется современное состояние вопроса изучения ганглиозных клеток сетчатки как мишени для терапии глаукомы, дается представление о новых подходах к лечению этого заболевания с использованием клеточных технологий на основе стратегии нейропротекции.
    corecore