Biomolecular Concepts最新文献

{"title":"Quantitative active super-resolution thermal imaging: The melanoma case study","authors":"M. Marini, M. Bouzin, R. Scodellaro, L. D’alfonso, L. Sironi, F. Granucci, F. Mingozzi, G. Chirico, M. Collini","doi":"10.1515/bmc-2022-0015","DOIUrl":"https://doi.org/10.1515/bmc-2022-0015","url":null,"abstract":"Abstract Super-resolution image acquisition has turned photo-activated far-infrared thermal imaging into a promising tool for the characterization of biological tissues. By the sub-diffraction localization of sparse temperature increments primed by the sample absorption of modulated focused laser light, the distribution of (endogenous or exogenous) photo-thermal biomarkers can be reconstructed at tunable ∼10−50 μm resolution. We focus here on the theoretical modeling of laser-primed temperature variations and provide the guidelines to convert super-resolved temperature-based images into quantitative maps of the absolute molar concentration of photo-thermal probes. We start from camera-based temperature detection via Stefan–Boltzmann’s law, and elucidate the interplay of the camera point-spread-function and pixelated sensor size with the excitation beam waist in defining the amplitude of the measured temperature variations. This can be accomplished by the numerical solution of the three-dimensional heat equation in the presence of modulated laser illumination on the sample, which is characterized in terms of thermal diffusivity, conductivity, thickness, and concentration of photo-thermal species. We apply our data-analysis protocol to murine B16 melanoma biopsies, where melanin is mapped and quantified in label-free configuration at sub-diffraction 40 µm resolution. Our results, validated by an unsupervised machine-learning analysis of hematoxylin-and-eosin images of the same sections, suggest potential impact of super-resolved thermography in complementing standard histopathological analyses of melanocytic lesions.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"242 - 255"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43306866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of cervical microbiome with epigenome of epithelial cells: Significance of inflammation to primary healthcare","authors":"V. Holubekova, Z. Kolková, I. Kasubova, Marek Samec, Alena Mazurakova, Lenka Koklesová, P. Kubatka, Tomas Rokos, E. Kozubík, K. Biringer, E. Kudela","doi":"10.1515/bmc-2022-0005","DOIUrl":"https://doi.org/10.1515/bmc-2022-0005","url":null,"abstract":"Abstract One pillar of the predictive, preventive, and personalized medicine framework strategies is the female health. The evaluation of women’s lifestyle and dietary habits in context with genetic and modifiable risk factors may reflect the prevention of cervical cancer before the occurrence of clinical symptoms and prediction of cervical lesion behavior. The main aim of this review is to analyze publications in the field of precision medicine that allow the use of research knowledge of cervical microbiome, epigenetic modifications, and inflammation in potential application in clinical practice. Personalized approach in evaluating patient’s risk of future development of cervical abnormality should consider the biomarkers of the local microenvironment characterized by the microbial composition, epigenetic pattern of cervical epithelium, and presence of chronic inflammation. Novel sequencing techniques enable a more detailed characterization of actual state in cervical epithelium. Better understanding of all changes in multiomics level enables a better assessment of disease prognosis and selects the eligible targeted therapy in personalized medicine. Restoring of healthy vaginal microflora and reversing the outbreak of cervical abnormality can be also achieved by dietary habits as well as uptake of prebiotics, probiotics, synbiotics, microbial transplantation, and others.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"61 - 80"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41386984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The phosphoinositide PI(3,5)P2 inhibits the activity of plant NHX proton/potassium antiporters: Advantages of a novel electrophysiological approach","authors":"A. Gradogna, J. M. Pardo, A. Carpaneto","doi":"10.1515/bmc-2022-0009","DOIUrl":"https://doi.org/10.1515/bmc-2022-0009","url":null,"abstract":"Abstract In the present work, we discuss the way in which the parallel application of the patch-clamp technique and the 2′,7′-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) fluorescence detection for recording luminal proton changes allows the functional characterization of nonelectrogenic potassium/proton vacuolar antiporters of the NHX (Na+/H+ exchanger) family. Moreover, we review the functional role of the tonoplast-specific phosphoinositide PI(3,5)P2, able to simultaneously inhibit the activity of NHXs and CLC-a transporters, whose coordinated action can play an important role in the water balance of plant cells.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"119 - 125"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46403111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative light sources for phototherapy","authors":"G. Romano, G. Insero, Santiago Nonell Marrugat, F. Fusi","doi":"10.1515/bmc-2022-0020","DOIUrl":"https://doi.org/10.1515/bmc-2022-0020","url":null,"abstract":"Abstract The use of light for therapeutic purposes dates back to ancient Egypt, where the sun itself was an innovative source, probably used for the first time to heal skin diseases. Since then, technical innovation and advancement in medical sciences have produced newer and more sophisticated solutions for light-emitting sources and their applications in medicine. Starting from a brief historical introduction, the concept of innovation in light sources is discussed and analysed, first from a technical point of view and then in the light of their fitness to improve existing therapeutic protocols or propose new ones. If it is true that a “pure” technical advancement is a good reason for innovation, only a sub-system of those advancements is innovative for phototherapy. To illustrate this concept, the most representative examples of innovative light sources are presented and discussed, both from a technical point of view and from the perspective of their diffusion and applications in the clinical field.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"256 - 271"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43759301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-temperature librations and dynamical transition in proteins at differing hydration levels","authors":"Erika Aloi, R. Bartucci, R. Guzzi","doi":"10.1515/bmc-2022-0007","DOIUrl":"https://doi.org/10.1515/bmc-2022-0007","url":null,"abstract":"Abstract Hydration of water affects the dynamics and in turn the activity of biomacromolecules. We investigated the dependence of the librational oscillations and the dynamical transition on the hydrating conditions of two globular proteins with different structure and size, namely β-lactoglobulin (βLG) and human serum albumin (HSA), by spin-label electron paramagnetic resonance (EPR) in the temperature range of 120–270 K. The proteins were spin-labeled with 5-maleimide spin-label on free cysteins and prepared in the lyophilized state, at low (h = 0.12) and full (h = 2) hydration levels in buffer. The angular amplitudes of librations are small and almost temperature independent for both lyophilized proteins. Therefore, in these samples, the librational dynamics is restricted and the dynamical transition is absent. In the small and compact beta-structured βLG, the angular librational amplitudes increase with temperature and hydrating conditions, whereas hydration-independent librational oscillations whose amplitudes rise with temperature are recorded in the large and flexible alpha-structured HSA. Both βLG and HSA at low and fully hydration levels undergo the dynamical transition at about 230 K. The overall results indicate that protein librational dynamics is activated at the low hydration level h = 0.12 and highlight biophysical properties that are common to other biosamples at cryogenic temperatures.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"81 - 88"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41642093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supercomplex supercomplexes: Raison d’etre and functional significance of supramolecular organization in oxidative phosphorylation","authors":"S. Nath","doi":"10.1515/bmc-2022-0021","DOIUrl":"https://doi.org/10.1515/bmc-2022-0021","url":null,"abstract":"Abstract Following structural determination by recent advances in electron cryomicroscopy, it is now well established that the respiratory Complexes I–IV in oxidative phosphorylation (OXPHOS) are organized into supercomplexes in the respirasome. Nonetheless, the reason for the existence of the OXPHOS supercomplexes and their functional role remains an enigma. Several hypotheses have been proposed for the existence of these supercomplex supercomplexes. A commonly-held view asserts that they enhance catalysis by substrate channeling. However, this – and other views – has been challenged based on structural and biophysical information. Hence, new ideas, concepts, and frameworks are needed. Here, a new model of energy transfer in OXPHOS is developed on the basis of biochemical data on the pure competitive inhibition of anionic substrates like succinate by the classical anionic uncouplers of OXPHOS (2,4-dinitrophenol, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and dicoumarol), and pharmacological data on the unique site-selective, energy-linked inhibition of energy conservation pathways in mitochondria induced by the guanidine derivatives. It is further found that uncouplers themselves are site-specific and exhibit differential selectivity and efficacy in reversing the inhibition caused by the Site 1/Complex I or Site 2/Complexes II–III-selective guanidine derivatives. These results lead to new vistas and sufficient complexity in the network of energy conservation pathways in the mitochondrial respiratory chain that necessitate discrete points of interaction with two classes of guanidine derivatives and uncoupling agents and thereby separate and distinct energy transfer pathways between Site 1 and Site 2 and the intermediate that energizes adenosine triphosphate (ATP) synthesis by Complex V. Interpretation based on Mitchell’s single-ion chemiosmotic theory that postulates only a single energy pool is inadequate to rationalize the data and account for the required complexity. The above results and available information are shown to be explained by Nath’s two-ion theory of energy coupling and ATP synthesis, involving coupled movement of succinate anions and protons, along with the requirement postulated by the theory for maintenance of homeostasis and ion translocation across the energy-transducing membrane of both succinate monoanions and succinate dianions by Complexes I–V in the OXPHOS supercomplexes. The new model of energy transfer in mitochondria is mapped onto the solved structures of the supercomplexes and integrated into a consistent model with the three-dimensional electron microscope computer tomography visualization of the internal structure of the cristae membranes in mammalian mitochondria. The model also offers valuable insights into diseased states induced in type 2 diabetes and especially in Alzheimer’s and other neurodegenerative diseases that involve mitochondrial dysfunction.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"272 - 288"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41928029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A photosensitizing fusion protein with targeting capabilities","authors":"S. Bruno, Marilena Margiotta, Marco Cozzolino, P. Bianchini, A. Diaspro, L. Cavanna, M. Tognolini, S. Abbruzzetti, C. Viappiani","doi":"10.1515/bmc-2022-0014","DOIUrl":"https://doi.org/10.1515/bmc-2022-0014","url":null,"abstract":"Abstract The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors. Fe-protoporphyrin IX was replaced by the photosensitizing compound Zn-protoporphyrin IX. Taking advantage of the fluorescence emission by Zn-protoporphyrin IX, we show that the construct can bind prostate cancer cells where the VPAC receptors are expressed.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"175 - 182"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49139331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffusion of molecules through nanopores under confinement: Time-scale bridging and crowding effects via Markov state model","authors":"I. Bodrenko, S. Milenkovic, M. Ceccarelli","doi":"10.1515/bmc-2022-0019","DOIUrl":"https://doi.org/10.1515/bmc-2022-0019","url":null,"abstract":"Abstract Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits the presence of molecules in its interior. The molecule–pore interaction is treated within the diffusion approximation by introducing the potential of mean force and the local diffusion coefficient for a correct statistical description. The crowding effect can be handled within the Markov state model approximation. By combining the two methods, one can deal with complex free energy surfaces taking into account crowding effects. We recapitulate the equations bridging the two models to calculate passive currents assuming a limited occupancy of the nanopore in a wide range of molecular concentrations. Several simple models are analyzed to clarify the consequences of the model. Eventually, a biologically relevant case of transport of an antibiotic molecule through a bacterial porin is used to draw conclusions (i) on the effects of crowding on transport of small molecules through biological channels, and (ii) to demonstrate its importance for modelling of cellular transport.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"207 - 219"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48543533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is styrene competitive for dopamine receptor binding?","authors":"E. De Santis, V. Minicozzi, G. Rossi, F. Stellato, S. Morante","doi":"10.1515/bmc-2022-0016","DOIUrl":"https://doi.org/10.1515/bmc-2022-0016","url":null,"abstract":"Abstract The potential role of styrene oxide in altering the dopaminergic pathway in the ear is investigated by means of molecular docking and molecular dynamics simulations. We estimate the binding affinity of both styrene oxide and dopamine to the dopaminergic receptor DrD2 by computing the free-energy difference, ∆G, between the configuration where the ligand is bound to the receptor and the situation in which it is “infinitely” far away from it. The results show that the styrene oxide has a somewhat lower affinity for binding with respect to dopamine, which, however, may not be enough to prevent exogenous high concentration styrene oxide to compete with endogenous dopamine for DrD2 binding.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"200 - 206"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43572865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion channels and neuronal excitability in polyglutamine neurodegenerative diseases","authors":"Vladimir A. Martínez-Rojas, L. J. Juárez-Hernández, C. Musio","doi":"10.1515/bmc-2022-0018","DOIUrl":"https://doi.org/10.1515/bmc-2022-0018","url":null,"abstract":"Abstract Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"183 - 199"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46331796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}