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1
Asner, Gregory P. « Biophysical and Biochemical Sources of Variability in Canopy Reflectance ». Remote Sensing of Environment 64, no 3 (juin 1998) : 234–53. http://dx.doi.org/10.1016/s0034-4257(98)00014-5.
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Enemchukwu, Nduka O., Ricardo Cruz-Acuña, Tom Bongiorno, Christopher T. Johnson, José R. García, Todd Sulchek et Andrés J. García. « Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis ». Journal of Cell Biology 212, no 1 (28 décembre 2015) : 113–24. http://dx.doi.org/10.1083/jcb.201506055.
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Epithelial cells cultured within collagen and laminin gels proliferate to form hollow and polarized spherical structures, recapitulating the formation of a rudimentary epithelial organ. However, the contributions of extracellular matrix (ECM) biochemical and biophysical properties to morphogenesis are poorly understood because of uncontrolled presentation of multiple adhesive ligands, limited control over mechanical properties, and lot-to-lot compositional variability in these natural ECMs. We engineered synthetic ECM-mimetic hydrogels with independent control over adhesive ligand density, mechanical properties, and proteolytic degradation to study the impact of ECM properties on epithelial morphogenesis. Normal cyst growth, polarization, and lumen formation were restricted to a narrow range of ECM elasticity, whereas abnormal morphogenesis was observed at lower and higher elastic moduli. Adhesive ligand density dramatically regulated apicobasal polarity and lumenogenesis independently of cell proliferation. Finally, a threshold level of ECM protease degradability was required for apicobasal polarity and lumen formation. This synthetic ECM technology provides new insights into how cells transduce ECM properties into complex morphogenetic behaviors.
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Unger, N., K. Harper, Y. Zheng, N. Y. Kiang, I. Aleinov, A. Arneth, G. Schurgers et al. « Photosynthesis-dependent isoprene emission from leaf to planet in a global carbon–chemistry–climate model ». Atmospheric Chemistry and Physics Discussions 13, no 7 (4 juillet 2013) : 17717–91. http://dx.doi.org/10.5194/acpd-13-17717-2013.
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Abstract. We describe the implementation of a biochemical model of isoprene emission that depends on the electron requirement for isoprene synthesis into the Farquhar/Ball–Berry leaf model of photosynthesis and stomatal conductance that is embedded within a global chemistry–climate simulation framework. The isoprene production is calculated as a function of electron transport-limited photosynthesis, intercellular carbon dioxide concentration, and canopy temperature. The vegetation biophysics module computes the photosynthetic uptake of carbon dioxide coupled with the transpiration of water vapor and the isoprene emission rate at the 30 min physical integration time step of the global chemistry–climate model. In the model, the rate of carbon assimilation provides the dominant control on isoprene emission variability over canopy temperature. A control simulation representative of the present day climatic state that uses 8 plant functional types (PFTs), prescribed phenology and generic PFT-specific isoprene emission potentials (fraction of electrons available for isoprene synthesis) reproduces 50% of the variability across different ecosystems and seasons in a global database of 28 measured campaign-average fluxes. Compared to time-varying isoprene flux measurements at 9 select sites, the model authentically captures the observed variability in the 30 min average diurnal cycle (R2= 64–96%) and simulates the flux magnitude to within a factor of 2. The control run yields a global isoprene source strength of 451 Tg C yr-1 that increases by 30% in the artificial absence of plant water stress and by 55% for potential natural vegetation.
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Unger, N., K. Harper, Y. Zheng, N. Y. Kiang, I. Aleinov, A. Arneth, G. Schurgers et al. « Photosynthesis-dependent isoprene emission from leaf to planet in a global carbon-chemistry-climate model ». Atmospheric Chemistry and Physics 13, no 20 (22 octobre 2013) : 10243–69. http://dx.doi.org/10.5194/acp-13-10243-2013.
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Abstract. We describe the implementation of a biochemical model of isoprene emission that depends on the electron requirement for isoprene synthesis into the Farquhar–Ball–Berry leaf model of photosynthesis and stomatal conductance that is embedded within a global chemistry-climate simulation framework. The isoprene production is calculated as a function of electron transport-limited photosynthesis, intercellular and atmospheric carbon dioxide concentration, and canopy temperature. The vegetation biophysics module computes the photosynthetic uptake of carbon dioxide coupled with the transpiration of water vapor and the isoprene emission rate at the 30 min physical integration time step of the global chemistry-climate model. In the model, the rate of carbon assimilation provides the dominant control on isoprene emission variability over canopy temperature. A control simulation representative of the present-day climatic state that uses 8 plant functional types (PFTs), prescribed phenology and generic PFT-specific isoprene emission potentials (fraction of electrons available for isoprene synthesis) reproduces 50% of the variability across different ecosystems and seasons in a global database of 28 measured campaign-average fluxes. Compared to time-varying isoprene flux measurements at 9 select sites, the model authentically captures the observed variability in the 30 min average diurnal cycle (R2 = 64–96%) and simulates the flux magnitude to within a factor of 2. The control run yields a global isoprene source strength of 451 TgC yr−1 that increases by 30% in the artificial absence of plant water stress and by 55% for potential natural vegetation.
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Haupt, Christian. « The AL Amyloid Fibril : Looking for a Link between Fibril Formation and Structure ». Hemato 2, no 3 (6 août 2021) : 505–14. http://dx.doi.org/10.3390/hemato2030032.
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The formation and deposition of fibrils derived from immunglobulin light chains is a hallmark of systemic AL amyloidosis. A particularly remarkable feature of the disease is the diversity and complexity in pathophysiology and clinical manifestations. This is related to the variability of immunoglobulins, as virtually every patient has a variety of mutations resulting in their own unique AL protein and thus a unique fibril deposited in the body. Here, I review recent biochemical and biophysical studies that have expanded our knowledge on how versatile the structure of AL fibrils in patients is and highlight their implications for the molecular mechanism of fibril formation in AL amyloidosis.
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Coward, Jesse, Matthew Hathorn, Volkan Karabacak, Orly Even Dar et Grégoire Altan-Bonnet. « Single-cell heterogeneity analysis provides rapid validation of biophysical parameters in living cells and quantifies heterogeneous sensitivity to interleukin-2, -7, and -15. (57.12) ». Journal of Immunology 186, no 1_Supplement (1 avril 2011) : 57.12. http://dx.doi.org/10.4049/jimmunol.186.supp.57.12.
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Abstract The single-cell resolution of flow cytometry provides a quantitative measurement of the heterogeneity of protein expression within clonal populations of cells. As the biological significance of this variability is becoming more widely appreciated, there is a need for new tools and methodology to analyze and leverage the effects of endogenous variation. These tools can provide alternatives to genetic methods, such as siRNA knockdown or germline knockout, that are commonly used to manipulate protein expression. We introduce such a new tool, named ScatterSlice, that enables rapid quantification of the correlation between heterogeneity in cellular responses (measured by staining of phospho-proteins) and varied expression of signaling molecules. We demonstrate its application to the validation of biochemical models of cellular responses to IL-2, IL-7, and IL-15 in living, unperturbed cells. In addition, we demonstrate that heterogeneous distribution of receptor subunits within a population of lymphocytes results in gradations of sensitivity to each cytokine. Finally, using experimental measurements of error and uncertainty in combination with biochemical models, we demonstrate the robustness of this analysis to experimental noise, and consider both limits and extensions to its use.
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La Gatta, Annalisa, Maria Aschettino, Antonietta Stellavato, Antonella D’Agostino, Valentina Vassallo, Emiliano Bedini, Gilberto Bellia et Chiara Schiraldi. « Hyaluronan Hydrogels for Injection in Superficial Dermal Layers : An In Vitro Characterization to Compare Performance and Unravel the Scientific Basis of Their Indication ». International Journal of Molecular Sciences 22, no 11 (2 juin 2021) : 6005. http://dx.doi.org/10.3390/ijms22116005.
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Background: Skinboosters represent the latest category of hyaluronan (HA) hydrogels released for aesthetic purposes. Different from originally developed gels, they are intended for more superficial injections, claiming a skin rejuvenation effect through hydration and possibly prompting biochemical effects in place of the conventional volumetric action. Here, three commercial skinboosters were characterized to unravel the scientific basis for such indication and to compare their performances. Methods: Gels were evaluated for water-soluble/insoluble-HA composition, rheology, hydration, cohesivity, stability and effect, in vitro, on human dermal fibroblasts towards the production of extracellular matrix components. Results: Marked differences in the insoluble-hydrogel amount and in the hydrodynamic parameters for water-soluble-HA chains were evidenced among the gels. Hydration, rigidity and cohesivity also varied over a wide range. Sensitivity to hyaluronidases and Reactive Oxygen Species was demonstrated allowing a stability ranking. Slight differences were found in gels’ ability to prompt elastin expression and in ColIV/ColI ratio. Conclusions. A wide panel of biophysical and biochemical parameters for skinboosters was provided, supporting clinicians in the conscious tuning of their use. Data revealed great variability in gels’ behavior notwithstanding the same clinical indication and unexpected similarities to the volumetric formulations. Data may be useful to improve customization of gel design toward specific uses.
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Bouanene, Houda, et Abdelhédi Miled. « Conflicting Views on the Molecular Structure of the Cancer Antigen CA125/MUC16 ». Disease Markers 28, no 6 (2010) : 385–94. http://dx.doi.org/10.1155/2010/918457.
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CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical and molecular nature of this antigen is poorly understood. Analysis of the structure of CA125 is essential for determining the physiological role of this very significant tumor marker. Accumulated experimental evidence has shown that CA125 epitopes reside on a molecule of very complex architecture in terms of both protein backbone and oligosaccharide structures. It is not clear whether the heterogeneity of CA125 molecular characteristics are due to the variability of biological sources from which the molecule was isolated or to the different biophysical methods used for the characterization of all the oligosaccharides linked to CA125 or to the presence of glycoisoforms for this protein. This review attempts to summarize emerging data related to molecular characteristics of CA125 and to compare approaches undertaken to reach a better understanding of molecular features of this tumor marker.
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Takagi, Jun, et Yuta Shimamoto. « High-quality frozen extracts of Xenopus laevis eggs reveal size-dependent control of metaphase spindle micromechanics ». Molecular Biology of the Cell 28, no 16 (août 2017) : 2170–77. http://dx.doi.org/10.1091/mbc.e17-03-0174.
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Cell-free extracts from unfertilized Xenopus laevis eggs offer the opportunity for a variety of biochemical and biophysical assays for analyzing essential cell cycle events such as metaphase spindle assembly. However, the extracts often exhibit substantial variation in quality and have low storage stability, factors that hamper their experimental utility. Here we report a simple two-step method for preparing frozen egg extracts that retain spindle assembly activity levels similar to those of freshly prepared extracts. Extract degradation associated with the freeze–thaw process can be substantially reduced by using centrifugal filter-based dehydration and slow sample cooling. Large amounts of frozen extract stocks from single-batch preparations allowed us to collect extensive data in micromanipulation experiments, which are often low-throughput, and thus enabled the clarification of correlations between metaphase spindle size and stiffness. Our method provides an assay platform with minimized biological variability and improves the accessibility of egg extracts for research.
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Morcillo-Pallarés, Pablo, Juan Pablo Rivera-Caicedo, Santiago Belda, Charlotte De Grave, Helena Burriel, Jose Moreno et Jochem Verrelst. « Quantifying the Robustness of Vegetation Indices through Global Sensitivity Analysis of Homogeneous and Forest Leaf-Canopy Radiative Transfer Models ». Remote Sensing 11, no 20 (18 octobre 2019) : 2418. http://dx.doi.org/10.3390/rs11202418.
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Vegetation indices (VIs) are widely used in optical remote sensing to estimate biophysical variables of vegetated surfaces. With the advent of spectroscopy technology, spectral bands can be combined in numerous ways to extract the desired information. This resulted in a plethora of proposed indices, designed for a diversity of applications and research purposes. However, it is not always clear whether they are sensitive to the variable of interest while at the same time, responding insensitive to confounding factors. Hence, to be able to quantify the robustness of VIs, a systematic evaluation is needed, thereby introducing a widest possible variety of biochemical and structural heterogeneity. Such exercise can be achieved with coupled leaf and canopy radiative transfer models (RTMs), whereby input variables can virtually simulate any vegetation scenario. With the intention of evaluating multiple VIs in an efficient way, this led us to the development of a global sensitivity analysis (GSA) toolbox dedicated to the analysis of VIs on their sensitivity towards RTM input variables. We identified VIs that are designed to be sensitive towards leaf chlorophyll content (LCC), leaf water content (LWC) and leaf area index (LAI) for common sensors of terrestrial Earth observation satellites: Landsat 8, MODIS, Sentinel-2, Sentinel-3 and the upcoming imaging spectrometer mission EnMAP. The coupled RTMs PROSAIL and PROINFORM were used for simulations of homogeneous and forest canopies respectively. GSA total sensitivity results suggest that LCC-sensitive indices respond most robust: for the great majority of scenarios, chlorophyll a + b content (Cab) drives between 75% and 82% of the indices’ variability. LWC-sensitive indices were most affected by confounding variables such as Cab and LAI, although the equivalent water thickness (Cw) can drive between 25% and 50% of the indices’ variability. Conversely, the majority of LAI-sensitive indices are not only sensitive to LAI but rather to a mixture of structural and biochemical variables.
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Pensalfini, Marco, et Adrian Buganza Tepole. « Mechano-biological and bio-mechanical pathways in cutaneous wound healing ». PLOS Computational Biology 19, no 3 (9 mars 2023) : e1010902. http://dx.doi.org/10.1371/journal.pcbi.1010902.
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Injuries to the skin heal through coordinated action of fibroblast-mediated extracellular matrix (ECM) deposition, ECM remodeling, and wound contraction. Defects involving the dermis result in fibrotic scars featuring increased stiffness and altered collagen content and organization. Although computational models are crucial to unravel the underlying biochemical and biophysical mechanisms, simulations of the evolving wound biomechanics are seldom benchmarked against measurements. Here, we leverage recent quantifications of local tissue stiffness in murine wounds to refine a previously-proposed systems-mechanobiological finite-element model. Fibroblasts are considered as the main cell type involved in ECM remodeling and wound contraction. Tissue rebuilding is coordinated by the release and diffusion of a cytokine wave, e.g. TGF-β, itself developed in response to an earlier inflammatory signal triggered by platelet aggregation. We calibrate a model of the evolving wound biomechanics through a custom-developed hierarchical Bayesian inverse analysis procedure. Further calibration is based on published biochemical and morphological murine wound healing data over a 21-day healing period. The calibrated model recapitulates the temporal evolution of: inflammatory signal, fibroblast infiltration, collagen buildup, and wound contraction. Moreover, it enables in silico hypothesis testing, which we explore by: (i) quantifying the alteration of wound contraction profiles corresponding to the measured variability in local wound stiffness; (ii) proposing alternative constitutive links connecting the dynamics of the biochemical fields to the evolving mechanical properties; (iii) discussing the plausibility of a stretch- vs. stiffness-mediated mechanobiological coupling. Ultimately, our model challenges the current understanding of wound biomechanics and mechanobiology, beside offering a versatile tool to explore and eventually control scar fibrosis after injury.
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Aguado-García, Alejandro, Daniel A. Priego-Espinosa, Andrés Aldana, Alberto Darszon et Gustavo Martínez-Mekler. « Mathematical model reveals that heterogeneity in the number of ion transporters regulates the fraction of mouse sperm capacitation ». PLOS ONE 16, no 11 (18 novembre 2021) : e0245816. http://dx.doi.org/10.1371/journal.pone.0245816.
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Capacitation is a complex maturation process mammalian sperm must undergo in the female genital tract to be able to fertilize an egg. This process involves, amongst others, physiological changes in flagellar beating pattern, membrane potential, intracellular ion concentrations and protein phosphorylation. Typically, in a capacitation medium, only a fraction of sperm achieve this state. The cause for this heterogeneous response is still not well understood and remains an open question. Here, one of our principal results is to develop a discrete regulatory network, with mostly deterministic dynamics in conjunction with some stochastic elements, for the main biochemical and biophysical processes involved in the early events of capacitation. The model criterion for capacitation requires the convergence of specific levels of a select set of nodes. Besides reproducing several experimental results and providing some insight on the network interrelations, the main contribution of the model is the suggestion that the degree of variability in the total amount and individual number of ion transporters among spermatozoa regulates the fraction of capacitated spermatozoa. This conclusion is consistent with recently reported experimental results. Based on this mathematical analysis, experimental clues are proposed for the control of capacitation levels. Furthermore, cooperative and interference traits that become apparent in the modelling among some components also call for future theoretical and experimental studies.
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Kobayashi, Tetsuya J., et Atsushi Kamimura. « 2SF-02 Information Processing via Noisy Biochemical Channels(2SF Inherent variability and information coding in biological systems,Symposium,The 50th Annual Meeting of the Biophysical Society of Japan) ». Seibutsu Butsuri 52, supplement (2012) : S14. http://dx.doi.org/10.2142/biophys.52.s14_1.
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Firozjaei, Mohammad Karimi, Solmaz Fathololoumi, Qihao Weng, Majid Kiavarz et Seyed Kazem Alavipanah. « Remotely Sensed Urban Surface Ecological Index (RSUSEI) : An Analytical Framework for Assessing the Surface Ecological Status in Urban Environments ». Remote Sensing 12, no 12 (24 juin 2020) : 2029. http://dx.doi.org/10.3390/rs12122029.
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Urban Surface Ecological Status (USES) reflects the structure and function of an urban ecosystem. USES is influenced by the surface biophysical, biochemical, and biological properties. The assessment and modeling of USES is crucial for sustainability assessment in support of achieving sustainable development goals such as sustainable cities and communities. The objective of this study is to present a new analytical framework for assessing the USES. This analytical framework is centered on a new index, Remotely Sensed Urban Surface Ecological index (RSUSEI). In this study, RSUSEI is used to assess the USES of six selected cities in the U.S.A. To this end, Landsat 8 images, water vapor products, and the National Land Cover Database (NLCD) land cover and imperviousness datasets are downloaded for use. Firstly, Land Surface Temperature (LST), Wetness, Normalized Difference Vegetation Index (NDVI), and Normalized Difference Soil Index (NDSI) are derived by remote sensing methods. Then, RSUSEI is developed by the combination of NDVI, NDSI, Wetness, LST, and Impervious Surface Cover (ISC) with Principal Components Analysis (PCA). Next, the spatial variations of USES across the cities are evaluated and compared. Finally, the association degree of each parameter in the USES modeling is investigated. Results show that the spatial variability of LST, ISC, NDVI, NDSI, and Wetness is heterogeneous within and between cities. The mean (standard deviation) value of RSUSEI for Minneapolis, Dallas, Phoenix, Los Angeles, Chicago and Seattle yielded 0.58 (0.16), 0.54 (0.17), 0.47 (0.19), 0.63 (0.21), 0.50 (0.17), and 0.44 (0.19), respectively. For all the cities, PC1 included more than 93% of the surface information, which is contributed by greenness, moisture, dryness, heat, and imperviousness. The highest and lowest mean values of RSUSEI are found in “Developed, High intensity” (0.76) and “Developed, Open Space” (0.35) lands, respectively. The mean correlation coefficient between RSUSEI and LST, ISC, NDVI, NDSI, and Wetness, is 0.47, 0.97, −0.31, 0.17, and −0.27, respectively. The statistical significance of these correlations is confirmed at 95% confidence level. These results suggest that the association degree of ISC in USES modeling is the highest, despite the differences in land cover and biophysical characteristics in the cities. RSUSEI could be very useful in modeling and comparing USES across cities with different geographical, climatic, environmental, and biophysical conditions and can also be used for assessing urban sustainability over space and time.
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Sanchez, Larysa, Erin Moshier, Alexander Coltoff, Ali Mustafa, Darren Pan, Hearn Jay Cho, Sundar Jagannath et al. « Outcomes in Multiple Myeloma Patients Progressing on Lenalidomide Maintenance ». Blood 134, Supplement_1 (13 novembre 2019) : 1779. http://dx.doi.org/10.1182/blood-2019-128441.
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Introduction: Lenalidomide (R) maintenance therapy in multiple myeloma (MM) has been shown to improve progression-free survival (PFS) and overall survival (OS) after autologous stem-cell transplantation (ASCT). Even in the transplant ineligible population, R until progression is associated with improved PFS. The ever-increasing use of R maintenance therapy, however, eventually leads to refractoriness to R at maintenance doses. Moreover, clinical trials with len-dex (Rd) backbone regimens including daratumumab, elotuzumab, ixazomib, and carfilzomib have all excluded such patients (pts). This is particularly an issue for elotuzumab and ixazomib, which have no single agent approval. There are currently no published data on the outcomes of full dose Rd or Rd backbone containing regimens in pts refractory to R maintenance. A prospective randomized trial would be difficult to perform given variability in pt factors (i.e. R tolerance, age, renal function) and disease factors (i.e. molecular risk and clinical vs biochemical progression). We therefore performed a retrospective study to characterize outcomes of pts on R maintenance therapy. Methods: This is a single-institution, retrospective study in which we reviewed the records of all consecutive pts with a diagnosis of MM at the Mount Sinai Hospital between February 2010 and October 2016. There were 465 pts identified who had maintenance R as a single agent or in combination with low-dose dexamethasone or prednisone. Pts were excluded if insufficient data were available or < 3 month (mo) follow up from time of initiation of R maintenance. Time to progression (TTP) on R maintenance, next line of therapy, and PFS on next line of therapy were determined using Kaplan Meyer analysis. Results: A total of 350 pts were included in this study. Baseline characteristics are summarized in Table 1. The median follow up time was 59 mos and median time on R maintenance was 21.0 mos. 172 pts (49%) progressed while on R maintenance or within 60 days of R discontinuation. 51 pts (15%) remain on R maintenance as of last follow up. The remaining 127 pts (36%) discontinued R for reasons other than progression and either progressed after 60 days (median 658 days, range 91-2053 days) or have not progressed. The median TTP on R maintenance was 34.2 mos (Fig 1A) and the majority of these were characterized by the treating physician as biochemical (65% during maintenance and 56% after R discontinuation). Of the patients with serologic and symptomatic progression, the majority were by bone disease (24% and 37%, respectively). 234 pts had data available on next line of therapy and the median PFS on this next line was 16.8 mo (95% CI: 13.2-20.1), however the PFS was shorter for those who had progressed while on R maintenance versus those who had progressed after R maintenance had been discontinued (13.2 mos vs. 28.9 mos, respectively, p 0.0001). The median PFS according to next line of therapy for those who received an increase in R dose + dex vs 3rd agent added to Rd backbone vs total change in therapy was 9.5 mos vs 21.0 mos vs 14.2 mos, respectively (Fig 1B). The most common drugs added to an Rd backbone were bortezomib and elotuzumab with an associated PFS of 19.0 and 40.1 mos, respectively. The majority of those receiving elotuzumab + Rd had progressed on R maintenance (15/18 = 83%). The most common regimens for those with a total change in therapy are summarized in Table 2. Conclusions: The median TTP on R maintenance was 34.2 mos and while most progression was felt to be biochemical, of those with symptomatic progression as well, the primary manifestation was bone disease (approximately 30% of patients), highlighting the importance of surveillance osseous imaging in MM. While an increase in R dose with steroids was associated with an additional 9.5 mos PFS and a total change in regimen with 14.2 mos PFS, those who received an Rd containing triplet had impressive results. In particular, Rd + elotuzumab resulted in a PFS of 40.1 mos. Multivariate analysis accounting for the potential confounding patient and disease factors inherent to treatment selection in retrospective studies will be presented at the meeting. Disclosures Cho: BMS: Consultancy; GSK: Consultancy; Takeda: Research Funding; The Multiple Myeloma Research Foundation: Employment; Genentech: Honoraria, Research Funding; Agenus: Research Funding; Celgene: Honoraria, Research Funding. Jagannath:Celgene: Consultancy; Novartis: Consultancy; Merck: Consultancy; Medicom: Speakers Bureau; Multiple Myeloma Research Foundation: Speakers Bureau; BMS: Consultancy. Madduri:Abbvie: Consultancy; Takeda: Consultancy; Celgene: Consultancy; undation Medicine: Consultancy. Parekh:Celgene Corporation: Research Funding; Karyopharm Inc.: Research Funding; Foundation Medicine Inc.: Consultancy. Richter:Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Speakers Bureau; Bristol-Meyers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Chari:Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; GlaxoSmithKline: Research Funding; Novartis Pharmaceuticals: Research Funding; Oncoceutics: Research Funding; Pharmacyclics: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Ballesteros, Daniel, Hugh W. Pritchard et Christina Walters. « Dry architecture : towards the understanding of the variation of longevity in desiccation-tolerant germplasm ». Seed Science Research 30, no 2 (juin 2020) : 142–55. http://dx.doi.org/10.1017/s0960258520000239.
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AbstractDesiccation-tolerant (DT) plant germplasm (i.e. seeds, pollen and spores) survive drying to low moisture contents, when cytoplasm solidifies, forming a glass, and chemical reactions are slowed. DT germplasm may survive for long periods in this state, though inter-specific and intra-specific variation occurs and is not currently explained. Such variability has consequences for agriculture, forestry and biodiversity conservation. Longevity was previously considered in the context of morphological features, cellular constituents or habitat characteristics. We suggest, however, that a biophysical perspective, which considers the molecular organization – or structure – within dried cytoplasm, can provide a more integrated understanding of the fundamental mechanisms that control ageing rates, hence the variation of longevity among species and cell types. Based on biochemical composition and physical–chemical properties of dried materials, we explore three types of the interplay between structural conformations of dried cytoplasm and ageing: (1) cells that lack chlorophyll and contain few storage lipids may exhibit long shelf life, with ageing probably occurring through slow autoxidative processes within the glassy matrix as it relaxes; (2) cells with active chlorophyll may die quickly, possibly because they are prone to oxidative stress promoted by the photosynthetic pigments in the absence of metabolic water and (3) cells that lack chloroplasts but contain high storage lipids may die quickly during storage at −20°C, possibly because lipids crystallize and destabilize the glassy matrix. Understanding the complex variation in structural conformation in space and time may help to design strategies that increase longevity in germplasm with generally poor shelf life.
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Frigerio, Roberto, Angelo Musicò, Marco Brucale, Andrea Ridolfi, Silvia Galbiati, Riccardo Vago, Greta Bergamaschi et al. « Extracellular Vesicles Analysis in the COVID-19 Era : Insights on Serum Inactivation Protocols towards Downstream Isolation and Analysis ». Cells 10, no 3 (4 mars 2021) : 544. http://dx.doi.org/10.3390/cells10030544.
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Since the outbreak of the COVID-19 crisis, the handling of biological samples from confirmed or suspected SARS-CoV-2-positive individuals demanded the use of inactivation protocols to ensure laboratory operators’ safety. While not standardized, these practices can be roughly divided into two categories, namely heat inactivation and solvent-detergent treatments. These routine procedures should also apply to samples intended for Extracellular Vesicles (EVs) analysis. Assessing the impact of virus-inactivating pre-treatments is therefore of pivotal importance, given the well-known variability introduced by different pre-analytical steps on downstream EVs isolation and analysis. Arguably, shared guidelines on inactivation protocols tailored to best address EVs-specific requirements will be needed among the analytical community, yet deep investigations in this direction have not yet been reported. We here provide insights into SARS-CoV-2 inactivation practices to be adopted prior to serum EVs analysis by comparing solvent/detergent treatment vs. heat inactivation. Our analysis entails the evaluation of EVs recovery and purity along with biochemical, biophysical and biomolecular profiling by means of a set of complementary analytical techniques: Nanoparticle Tracking Analysis, Western Blotting, Atomic Force Microscopy, miRNA content (digital droplet PCR) and tetraspanin assessment by microarrays. Our data suggest an increase in ultracentrifugation (UC) recovery following heat treatment; however, it is accompanied by a marked enrichment in EVs-associated contaminants. On the other hand, solvent/detergent treatment is promising for small EVs (<150 nm range), yet a depletion of larger vesicular entities was detected. This work represents a first step towards the identification of optimal serum inactivation protocols targeted to EVs analysis.
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Suarez, Luz Angelica, Andrew Robson, John McPhee, Julie O’Halloran et Celia van Sprang. « Accuracy of carrot yield forecasting using proximal hyperspectral and satellite multispectral data ». Precision Agriculture 21, no 6 (2 mai 2020) : 1304–26. http://dx.doi.org/10.1007/s11119-020-09722-6.
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Abstract Proximal and remote sensors have proved their effectiveness for the estimation of several biophysical and biochemical variables, including yield, in many different crops. Evaluation of their accuracy in vegetable crops is limited. This study explored the accuracy of proximal hyperspectral and satellite multispectral sensors (Sentinel-2 and WorldView-3) for the prediction of carrot root yield across three growing regions featuring different cropping configurations, seasons and soil conditions. Above ground biomass (AGB), canopy reflectance measurements and corresponding yield measures were collected from 414 sample sites in 24 fields in Western Australia (WA), Queensland (Qld) and Tasmania (Tas), Australia. The optimal sensor (hyperspectral or multispectral) was identified by the highest overall coefficient of determination between yield and different vegetation indices (VIs) whilst linear and non-linear models were tested to determine the best VIs and the impact of the spatial resolution. The optimal regression fit per region was used to extrapolate the point source measurements to all pixels in each sampled crop to produce a forecasted yield map and estimate average carrot root yield (t/ha) at the crop level. The latter were compared to commercial carrot root yield (t/ha) obtained from the growers to determine the accuracy of prediction. The measured yield varied from 17 to 113 t/ha across all crops, with forecasts of average yield achieving overall accuracies (% error) of 9.2% in WA, 10.2% in Qld and 12.7% in Tas. VIs derived from hyperspectral sensors produced poorer yield correlation coefficients (R2 < 0.1) than similar measures from the multispectral sensors (R2 < 0.57, p < 0.05). Increasing the spatial resolution from 10 to 1.2 m improved the regression performance by 69%. It is impossible to non-destructively estimate the pre-harvest spatial yield variability of root vegetables such as carrots. Hence, this method of yield forecasting offers great benefit for managing harvest logistics and forward selling decisions.
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Lamba, S. S., K. Y. Such et H. Lewis Ill. « The Potential Use of Hydroxyurea as Treatment for Sickle Cell Disease ». Current Medicinal Chemistry 1, no 5 (février 1995) : 366–75. http://dx.doi.org/10.2174/092986730105220216101649.
Texte intégralRésumé :
Abstract: Recent biochemical and biophysical studies of sickle cell hemoglobin have provided valuable insight into the molecular basis of the sickling phenomenon in sickle cell disease. A large number of compounds have been examined for antisickling potential. These can be characterized as noncovalent or covalent in their mechanism of action. Examples of noncovalent agents include: alkylureas, dimethyl sulfoxide, dimethylforma mide, small peptides, etc. Examples of covalent agents include: nitrogen mustard, glyceraldehyde, aldehydic pyridoxal derivatives, dimethyladipimidate, etc. Also, acylating agents such as acylsalicylates have been investigated. lnspite of such advances and attempts, a useful agent has not been successfully produced. Thus, sickle cell disease continues to be a serious health problem for which there is no cure, and the treatment remains to be symptomatic. Sickle cell disease includes a group of hereditary hemoglobin disorders characterized by red cells which undergo sickle shape transformation under hypoxic conditions. Due to the substitution of valine for glutamic acid in position 6 of the beta chain, sickle hemoglobin polymerizes when it is deoxygenated. The most clinically significant of these diseases is sickle cell anemia. Symptoms include dactylitis, painful crisis, splenic sequestration and the development of multi-organ damage and failure. Different clinical presentations of sickle cell anemia call for individualized management. The reason for such clinical variability is not known; although the patient's hemoglobin level as well as fetal hemoglobin (HbF) concentrations are important. New therapeutic approaches include the use of hydroxyurea which is reported to increase the level of fetal hemoglobin which interferes with polymer formation. Because fetal hemoglobin contains gammaglobin chains instead of beta chains, it is not affected by the genetic defect that causes sickle cell disease. Increased levels of fetal hemoglobin decrease the tendency toward intracellular polymerization of sickle hemoglobin that characterizes the disease. This review provides information regarding the role of fetal hemoglobin (HbF) and sickling; methodology for an accurate quantitation of HbF; recent pharmacological interventions; and includes results of selected clinical trials reported in recent years.
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Cole, John A., Joseph R. Peterson, Tyler M. Earnest, Micahel J. Hallock, John R. Pfeiffer, Tushar Pandey et Eduardo Braun. « SimBioSys TumorScope : Spatio-temporal modeling of the tumor microenvironment to predict chemotherapeutic response. » Journal of Clinical Oncology 38, no 15_suppl (20 mai 2020) : e12650-e12650. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e12650.
Texte intégralRésumé :
e12650 Background: One of the most important sources of variability affecting each patient’s response to neoadjuvant chemotherapy (NACT) is drug and nutrient perfusion, The SimBioSys TumorScope is a computational decision-support system that is designed to predict the flow of drugs and nutrients throughout the tumor microenvironment, and the subsequent response of the tumor to treatment. By enabling healthcare providers to simulate a range of different standard-of-care treatment regimens in a realistic 3D model of each patient’s tumor, providers can predict which treatments are most effective, and provide the best possible care for their patients. Methods: SimBioSys TumorScope implements a multi-scale simulation technology that couples several biophysical and biochemical models in order to predict how individual patients' tumors respond to NACT. The simulations explicitly track the 3D morphology of the tumor and surrounding tissues (based on MRI images), as well as the concentrations of key nutrients and drugs as they change over time. At each location within the 3D model, these concentrations are used to predict cell growth and death rates. As different regions of the tumor grow or die, its macroscopic shape changes. Results: SimBioSys TumorScope was retrospectively applied to over 300 breast cancer patients that received NACT. Simulations were initialized with pre-treatment MRI data, and run through the entirety of each patient's specified treatment regimen. Predicted changes in tumor volume and longest dimension were then compared against measured values at several time-points after initiation of therapy, yielding Pearson correlations of over 0.93 for both. Work is underway to extend the technology to lung tumors; early results show very different metabolic behaviors from those of breast tumors, and significantly less response to treatment overall. Conclusions: Through accurate spatio-temporal modeling of drug and nutrient perfusion, metabolic behavior, and the physico-chemical interactions that arise between tissues, the SimBioSys TumorScope for Breast Cancer can accurately predict the response of patients treated with NACT.
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Rossini, M., S. Cogliati, M. Meroni, M. Migliavacca, M. Galvagno, L. Busetto, E. Cremonese et al. « Remote sensing-based estimation of gross primary production in a subalpine grassland ». Biogeosciences Discussions 9, no 2 (10 février 2012) : 1711–58. http://dx.doi.org/10.5194/bgd-9-1711-2012.
Texte intégralRésumé :
Abstract. This study investigates the performances in a terrestrial ecosystem of gross primary production (GPP) estimation of a suite of spectral vegetation indexes (VIs) that can be computed from currently orbiting platforms. Vegetation indexes were computed from near-surface field spectroscopy measurements collected using an automatic system designed for high temporal frequency acquisition of spectral measurements in the visible near-infrared region. Spectral observations were collected for two consecutive years in Italy in a subalpine grassland equipped with an Eddy Covariance (EC) flux tower which provides continuous measurements of net ecosystem carbon dioxide (CO2) exchange (NEE) and the derived GPP. Different VIs were calculated based on ESA-MERIS and NASA-MODIS spectral bands and correlated with biophysical (Leaf Area Index, LAI; fraction of photosynthetically active radiation intercepted by green vegetation, fIPARg), biochemical (chlorophyll concentration) and ecophysiological (green light-use efficiency, LUEg) canopy variables. In this study, the normalized difference vegetation index (NDVI) showed better correlations with LAI and fPARg (r = 0.90 and 0.95, respectively), the MERIS terrestrial chlorophyll index (MTCI) with leaf chlorophyll content (r = 0.91) and the Photochemical Reflectance Index (PRI551), computed as (R531−R551)/(R531+R551) with LUEg (r = 0.64). Subsequently, these VIs were used to estimate GPP using different modelling solutions based on the light-use efficiency model describing the GPP as driven by the photosynthetically active radiation absorbed by green vegetation (APARg) and by the efficiency (ε) with which plants use the absorbed radiation to fix carbon via photosynthesis. Results show that GPP can be successfully modelled with a combination of VIs and meteorological data or VIs only. Vegetation indexes designed to be more sensitive to chlorophyll content explained most of the variability in GPP in the ecosystem investigated, characterized by a strong seasonal dynamic of GPP. Accuracy in GPP estimation slightly improves when taking into account high frequency modulations of GPP driven by incident PAR or modelling LUEg with the PRI in model formulation. Similar results were obtained for both measured daily VIs and VIs obtained as 16-day composite time series and then downscaled from the compositing period to daily scale (resampled data). However, the use of resampled data rather than measured daily input data decreases the accuracy of the total GPP estimation on an annual basis.
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Rossini, M., S. Cogliati, M. Meroni, M. Migliavacca, M. Galvagno, L. Busetto, E. Cremonese et al. « Remote sensing-based estimation of gross primary production in a subalpine grassland ». Biogeosciences 9, no 7 (12 juillet 2012) : 2565–84. http://dx.doi.org/10.5194/bg-9-2565-2012.
Texte intégralRésumé :
Abstract. This study investigates the performances in a terrestrial ecosystem of gross primary production (GPP) estimation of a suite of spectral vegetation indexes (VIs) that can be computed from currently orbiting platforms. Vegetation indexes were computed from near-surface field spectroscopy measurements collected using an automatic system designed for high temporal frequency acquisition of spectral measurements in the visible near-infrared region. Spectral observations were collected for two consecutive years in Italy in a subalpine grassland equipped with an eddy covariance (EC) flux tower that provides continuous measurements of net ecosystem carbon dioxide (CO2) exchange (NEE) and the derived GPP. Different VIs were calculated based on ESA-MERIS and NASA-MODIS spectral bands and correlated with biophysical (Leaf area index, LAI; fraction of photosynthetically active radiation intercepted by green vegetation, fIPARg), biochemical (chlorophyll concentration) and ecophysiological (green light-use efficiency, LUEg) canopy variables. In this study, the normalized difference vegetation index (NDVI) was the index best correlated with LAI and fIPARg (r = 0.90 and 0.95, respectively), the MERIS terrestrial chlorophyll index (MTCI) with leaf chlorophyll content (r = 0.91) and the photochemical reflectance index (PRI551), computed as (R531-R551)/(R531+R551) with LUEg (r = 0.64). Subsequently, these VIs were used to estimate GPP using different modelling solutions based on Monteith's light-use efficiency model describing the GPP as driven by the photosynthetically active radiation absorbed by green vegetation (APARg) and by the efficiency (ε) with which plants use the absorbed radiation to fix carbon via photosynthesis. Results show that GPP can be successfully modelled with a combination of VIs and meteorological data or VIs only. Vegetation indexes designed to be more sensitive to chlorophyll content explained most of the variability in GPP in the ecosystem investigated, characterised by a strong seasonal dynamic of GPP. Accuracy in GPP estimation slightly improves when taking into account high frequency modulations of GPP driven by incident PAR or modelling LUEg with the PRI in model formulation. Similar results were obtained for both measured daily VIs and VIs obtained as 16-day composite time series and then downscaled from the compositing period to daily scale (resampled data). However, the use of resampled data rather than measured daily input data decreases the accuracy of the total GPP estimation on an annual basis.
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Ivankova, V., E. Domina, T. Khrulenko, L. Baranovska et O. Hrinchenko. « IRIDIUM-192 RADIOTHERAPY BENEFITS IN THE MANAGEMENT OF GYNECOLOGICAL TUMORS ». Проблеми радіаційної медицини та радіобіології = Problems of Radiation Medicine and Radiobiology 25 (2020) : 569–78. http://dx.doi.org/10.33145/2304-8336-2020-25-569-578.
Texte intégralRésumé :
Background. Application of the most advanced radiation technologies of brachytherapy featuring the high dose rate sources i.e. 60Co and 192Ir within contemporary management protocols for gynecological cancer provides maximum dose distribution in the clinical target along with minimal radiation exposure on surrounding organs and tissues. It involves irradiation of large spaces with delivery of high therapeutic doses at the tolerance bound of «critical» organs (bladder, rectum) and tissues. Thus minimization of the early and late radiation complications, life span extent and quality of life increase remain just the issues in contemporary radiation oncology requiring therefore the elaboration of radiobiological criteria along with substantiation of physiсо-engineering properties of the radiation sources. Taking into account the basic radiobiological patterns will ensure a definitive further progress in the field of radiation oncology. Objective: to study and compare the biological effects of 192Ir with the effects of the reference gamma radiation 60Co and increase the effectiveness of brachytherapy using a 192Ir source. Materials and methods. Radiobiological dosimetry on the basis of a test system of peripheral blood lymphocytes from the gynecological cancer patients with subsequent cytogenetic analysis of radiation-induced chromosome aberrations was performed to study and compare the biological effects of 192Ir and reference 60Со γ-radiation, and to enhance the efficiency of 192Ir brachytherapy. Results. Radiation markers, i.e. dicentric chromosomes with an accompanying paired fragment prevailed in the spectrum of radiation-induced damage. Variability of individual cytogenetic parameters of peripheral lymphocytes upon the first fraction of irradiation at the same dose of 5 Gy indicated an individual sensitivity of patients to the 192Ir γ-irradiation. Comprehensive conservative treatment with adjuvant radiotherapy was applied to the patients (n = 98) having got secondary vaginal cancer stage II–III, T2-3N0-1M0. The high dose-rate (HDR) brachytherapy using 192Ir radiation sources was applied in the main study group (n = 37), HDR brachytherapy using 60Co radiation sources was applied in the control group (n = 35). Conclusion. The HDR brachytherapy with 192Ir and 60Co sources on the up-to-date technology intensive devices provides a high accuracy of dose distributions when irradiating the malignant neoplasms with minimized radiation exposure to the «critical» tissues. Treatment results are improved therefore. The use of 192Ir radiation sources compared with 60Co ones resulted in an increased throughput of treatment, enhanced tumor regression, and reduced incidence of radiation effects on the critical organs. Currently we perform the radiobiological studies on somatic cells from cancer patients at the genetic, biochemical, biophysical, and cytological levels in order to receive a biological indication of radiation damage under the impact of 192Ir isotope. Continuation of clinical trials with radiobiological support will provide an opportunity to predict the early and late radiation complications and thus to provide a personalized approach in brachytherapy of cancer patients using the 192Ir sources of γ-rays. Key words: HDR brachytherapy, 192Ir and 60Co high dose rate sources.
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Dean, Melinda M., Katrina Kildey, Thu V. Tran, Kelly Rooks, Shoma Baidya et Robert L. Flower. « Single Nucleotide Variations In Spectrin-1β Accentuate The Red Blood Cell Storage Lesion ». Blood 122, no 21 (15 novembre 2013) : 3422. http://dx.doi.org/10.1182/blood.v122.21.3422.3422.
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Abstract Introduction During routine storage packed red blood cells (PRBC) undergo biochemical and biophysical changes collectively referred to as the “RBC storage lesion”. Donor-to-donor variability in the severity of the storage lesion has been reported. The extent to which donor-associated differences in blood component storage affect blood product quality and post-transfusion outcome remains unknown. Murine models with single nucleotide variants (SNV) in gene encoding spectrin-1β were used to investigate the impact of mutations on the RBC storage lesion. Methods Two murine lineages with N-ethyl-N-nitrosourea (ENU) generated single SNV in Spnb1, encoding spectrin-1β (Table 1), were selected from the Australian Phenomics Facility library (http://databases.apf.edu.au/mutations). Using genetic selection, homozygous (HOM), heterozygous (HET) and unaffected (WT) mice from each strain were generated (C57BL/6 background strain). Murine blood was leucoreduced, prepared in SAGM (0.4 HCT) and stored at 4°C for time course assessment of RBC characteristics. At day (D), D2, D7, D14 and D21 of storage, RBC integrity and evidence of storage-related changes were investigated using RBC osmotic fragility and flow cytometric analysis of CD44, CD47, TER119 and phosphatidylserine (PS). Data were generated from analysis of blood from Spnb1 (pedigree spectrin-1β a) homozygous (HOM, n=3), heterozygous (HET, n=3) and unaffected (WT, n=2 ); Spnb1 (pedigree spectrin-1β b) HOM (n=4), HET( n=4); C57BL/6 (n=4). The Mann-Whitney Test and ANOVA were utilised for statistical analyses (95% CI). Results At D2 of storage SNV in Spnb1 did not alter RBC characteristics, with all mice studied demonstrating a similar resistance to osmotic lysis and levels of CD44, CD47, TER119 and PS. By D7 of storage, clear pedigree-related differences in RBC characteristics were evident. At D7, RBC from spectrin-1β(a) HOM mice had significantly increased osmotic fragility and exposure of PS as well as significantly reduced CD44 and TER119 expression compared to unaffected siblings and background strain. Of note, these changes were not evident in the spectrin-1β(b) HOM mice at D7. For both strains at D7, heterozygous SNV did not exhibit altered storage parameters. By D14 both HOM and HET spectrin-1β(a) mice demonstrated a phenotype consistent with an exacerbated RBC storage lesion, characterised by significantly increased osmotic fragility and exposure of PS, and reduced CD44 and CD47 compared to background strain. At D14 there was also evidence of exacerbation of the storage lesion in stored RBC from HOM spectrin-1β(b) mice (significantly increased PS), though this was not to the extent observed in the spectrin-1β(a) mice. By D21 all murine RBC were substantially degraded under these storage conditions. Conclusions SNV in Spnb1,encoding RBC structural protein spectrin-1β, resulted in both early onset and exacerbation of the RBC storage lesion. Further, the degree of storage lesion and the point at which RBC degradation was observed was not only dependent on the homozygous or heterozygous status, but the mutation itself. These data demonstrate that minor genetic variation in genes encoding important RBC proteins contribute to donor related differences in PRBC storage. Disclosures: No relevant conflicts of interest to declare.
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Dean, Melinda M., Luke D. Samson, Kelly Rooks, Jesse Fryk, Shoma Baidya et Robert L. Flower. « Donor Variation In Biological Mediators During Storage Of Packed Red Blood Cells ». Blood 122, no 21 (15 novembre 2013) : 3655. http://dx.doi.org/10.1182/blood.v122.21.3655.3655.
Texte intégralRésumé :
Abstract Introduction During routine storage, packed red blood cells (PRBC) undergo numerous biochemical and biophysical changes collectively referred to as the “RBC storage lesion”. A number of factors reported to accumulate during the routine storage of PRBCs are hypothesized to mediate inflammatory cell responses and contribute to poor patient outcomes following transfusion. In addition, donor variability in red blood cell (RBC) characteristics and onset of the storage lesion has been reported. We investigated changes in levels of potential biological response modifies in the supernatant (SN) of PRBC relevant to storage, and, variance between donations. Methods Cytometric bead array was utilised to quantify a panel of 32 potential biological response modifiers (BRMs) in the SN of PRBC during storage. Potential BRMS were analysed in the SN of 8 leukodepleted PRBC units at weekly intervals (D2, D7, D14, D21, D28, D35, D42). The CBA panel was comprised of soluble(s) CD40 Ligand, sCD62E, sCD62L, sCD14, sCD54 (ICAM-1), sCD106 (VCAM-1), CXCL9, VEGF, Fractalkine (CX3CL1), IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α, MIP-1α, MIP-1β, IP-10, RANTES, sCD62P, IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-9, IL-13, IFN-α, IFN-γ, angiogenin, MCP-1. Storage related changes were analysed using ANOVA (95% CI). Donor variance was indicated by fold difference and range. “High” sub population of donations compared to remaining donations at each time point using Mann-Whitney (95% CI). Results Of the 32 potential BRMs studied, angiogenin, sCD14, sCD106 (VCAM-1), sCD62L, sCD62P, ICAM-1, IL-1α, IP-10, RANTES and IL-9 were consistently detected in all units throughout the time course. There was no evidence of a storage related increase in these biological mediators during storage of the PRBC, although angiogenin levels significantly declined during storage (P<0.001, ANOVA). Of particular interest, the concentrations of these nine biological mediators varied greatly between the individual PRBC units. ICAM-1, VCAM-1 and IL-1α concentrations each varied 10 fold between units (range 1000 – 10 000 pg/mL for each), sCD14 varied 5 fold (range 20 000 - 100 000 pg/mL), sCD62L varied 4.4 fold (range 9000 – 40 000 pg/mL), and sCD62P varied 6.5 fold (range 200 -1300 pg/ml). In addition, it was apparent that a sub population (3/8) of the units assessed consistently had the highest levels of ICAM-1, sCD106 (VCAM-1), sCD14, sCD62L, IL-1α, sCD62P and angiogenin. For sCD62P, in particular, this “high” sub population had significantly different levels of sCD62P at each time point compared to the other five units (P<0.05 at each time point). The remaining BRMs studied were at the limits of detection (<20 pg/mL) for every unit at each time point, and no storage related changes were evident. Conclusions There was minimal change in the BRMs studied relevant to storage duration of the PRBC units. The most notable differences in the levels of biological mediators present in PRBC SN were due to donor-to-donor variation. These data suggest high levels of BRMs and potential immune modulation in transfusion recipients may be the result of donor-associated differences rather than storage-associated differences in blood components. Disclosures: No relevant conflicts of interest to declare.
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Islamzada, Emel, Kerryn Matthews, Erik Lamoureux, Mark D. Scott et Hongshen Ma. « Degradation of Red Blood Cell Deformability during Cold Storage in Blood Bags ». Blood 138, Supplement 1 (5 novembre 2021) : 2143. http://dx.doi.org/10.1182/blood-2021-153760.
Texte intégralRésumé :
Abstract RBC transfusions are a life-saving procedure, aiding both chronic and acute patients in restoring tissue oxygenation. The ability to store collected RBC units for prolonged periods has been one of the most transformative advances in medicine, significantly improving the reliability and the speed of access to blood. However, RBCs undergo a number of metabolic, structural, and biochemical changes during storage, collectively known as the storage lesion, that is detrimental to the quality of the RBC. A major challenge is the ability to evaluate the extent of the storage lesion, and thus the quality of the stored RBC unit directly prior to transfusion. The storage lesion can directly or indirectly reduce the ability of the RBC to deform through the small openings in the microvasculature. Rigid RBCs pose a risk of sequestration in capillaries, impeding blood flow and reducing tissue oxygenation, and are more likely to be cleared out by endothelial macrophages. Studies have shown that there is a loss in RBC deformability during storage and that the rate of RBC deformability loss is donor-dependent. Thus, RBC deformability can be a valuable and reliable biophysical marker of RBC unit quality. Currently, there is a need for a reliable measurement technique that is repeatable and sensitive enough to observe individual differences in RBC deformability in healthy donors, to enable quality control testing of RBC units. We have developed the microfluidic ratchet device, which sorts RBCs based on their deformability, allowing the measurement of both rigid and deformable sup-populations of RBCs within the sample, and generating a unique deformability curve. Here, we use this assay to predict the quality of stored RBC units. We assessed the deformability of 14 healthy donor RBC units through 8 weeks of cold storage at 4°C, which is 2 weeks beyond the Canadian Blood Services approved 6-week standard in Canada. We measured RBC deformability, standard hematological parameters (MCV, MCHC, MCH, and RDW), and hemolysis levels at the time of RBC unit manufacture (week 0), followed by weeks 2, 4, 6, and 8. The microfluidic ratchet device operates by forcing RBCs to deform and travel through rows of tapered constrictions. Constriction size changes from 7.5 to 1.5 µm and is reflective of the microvasculature and vessel opening sizes encountered by RBCs in circulation. RBCs are sorted into 12 distinct outlets based on their deformability. Distribution of RBCs in outlets 1-12 can be quantified and used to calculate the cumulative distribution curve. The cumulative distribution curve provides a distinct deformability signature of each individual RBC sample, which can be defined as rigidity score (RS). RS provides an easy metric to compare the changes in RBC deformability throughout storage (ΔRS) in a single donor as well as across multiple donors. We show that there are both donor- and sex-specific differences in the RBC deformability signatures of stored RBC units. We observed significant inter-donor variability in RBC deformability measured on the day of the RBC unit manufacture, where male donors showed a more stable RBC deformability range (n=8, RS=3.00±0.18) compared to female donors (n=6, RS= 3.29±0.48). The average RS scores were stable between weeks 0-2 (ΔRS 0.07) and showed a reduction in deformability between weeks 1-6 (ΔRS 0.35), with the greatest loss seen between weeks 6-8 (ΔRS 0.42) of cold storage. Interestingly, the response to cold storage is variable, with ΔRS 0.22 to 0.90, suggesting that some donors are more susceptible to storage related changes in RBC deformability than others. Notably, the change in RS over time was donor-specific and did not correlate with RBC deformability at week 0. The majority of RBCs from male donors (ΔRS 0.485, p<0.05), but none of the female donors (ΔRS 0.172) showed changes in deformability during cold storage, suggesting that RBCs from female donors degrade at a slower rate compared to RBCs from male donors. The ability to profile RBC deformability at the individual blood bag level may help identify more stable RBCs for use in chronic and sensitive patients, or RBC units that can be safely stored beyond the 6-week storage window. Disclosures No relevant conflicts of interest to declare.
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Lin, Shuyu, Jialun Zhu, Wenzhuo Yu, Bo Wang, Kiarash A. Sabet, Yichao Zhao, Xuanbing Cheng et al. « A touch-based multimodal and cryptographic bio-human–machine interface ». Proceedings of the National Academy of Sciences 119, no 15 (4 avril 2022). http://dx.doi.org/10.1073/pnas.2201937119.
Texte intégralRésumé :
Significance The awareness of the individuals’ biological status is critical for creating interactive environments. Accordingly, we devised a multimodal cryptographic bio-human–machine interface (CB-HMI), which seamlessly translates touch-based entries into encrypted biochemical, biophysical, and biometric indices (i.e., circulating biomarkers levels, heart rate, oxygen saturation level, and fingerprint pattern). As its central component, the CB-HMI features thin hydrogel-coated chemical sensors and a signal interpretation framework to access/interpret biochemical indices, bypassing the challenge of circulating analyte accessibility and the confounding effect of pressing force variability. Upgrading the surrounding objects with CB-HMI, we demonstrated new interactive solutions for driving safety and medication use, where the integrated CB-HMI uniquely enabled one-touch bioauthentication (based on the user’s biological state/identity), prior to rendering the intended services.
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Rossi, Federica, Luigi Manfrini, Melissa Venturi, Luca Corelli Grappadelli et Brunella Morandi. « Fruit transpiration drives interspecific variability in fruit growth strategies ». Horticulture Research 9 (2022). http://dx.doi.org/10.1093/hr/uhac036.
Texte intégralRésumé :
Abstract Fruit growth is a complex mechanism resulting from biochemical and biophysical events leading water and dry matter to accumulate in the fruit tissues. Understanding how fruits choose their growth strategies can help growers optimizing their resource management for a more sustainable production and a higher fruit quality. This paper compares the growth strategies adopted by different fruit crops, at different times during the season and relates their fruit surface conductance to key physiological parameters for fruit growth such as phloem and xylem inflows as well transpiration losses. Our results show how fruits capacity to transpire (determined by their surface conductance) is a key driver in determining the growth strategy adopted by a species and explains the inter-species variability existing among different crops. Indeed, fruits change their surface conductance depending on the species and the phenological stage. This has an impact on the fruit’s ability to lose water due to transpiration, affecting fruit pressure potential and increasing the force with which the fruit is able to attract xylem and phloem flows, with a considerable impact on fruit growth rate.
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Anvesh, K., Shivani Choudhary, K. C. Kumawat, G. K. Mittal et Kiran Gaur. « Morphological and Biochemical Basis of Resistance in Indian Bean, Lablab purpureus var. typicus (L.) Sweet Varieties against Pod Borers ». LEGUME RESEARCH - AN INTERNATIONAL JOURNAL, Of (10 août 2021). http://dx.doi.org/10.18805/lr-4665.
Texte intégralRésumé :
Background: Indian bean, Lablab purpureus var. typicus (L.) Sweet (family: Fabaceae) is an important vegetable crop in India and other countries. The main reasons of variability in the pattern of resistance shown by different genotypes were explained by Painter (1951). Antibiosis is an adverse impact of the host plant on the biology of the insect pests and their progeny due to the biochemical and biophysical factors present in it. Methods: The experiment was laid out in a simple randomized block design (RBD) with seven treatments, each replicated thrice. The plot size was 1.8x1.8 m2 keeping row to row and plant to plant distance of 45 cm each. The Indian bean varieties, Arka Jay, Konkan Bhushan, Diana, Bauni, Pari, JK Special and Ganganagar local were sown on 25th July in Kharif, 2019 (July-November). Horticulture Farm of S.K.N. College of Agriculture, Jobner (Rajasthan). The recommended package of practices was followed to raise the crop. Various morphological parameters, viz., pod length, pod width, pod shell thickness, pod weight and number of seeds per pod were noted. The biochemical parameters, viz., moisture content, phenol content, total sugars, total protein and fibre content were analyzed. Result: The results obtained were subjected to correlation and regression analysis to draw the impact of these parameters on pod damage. Morphological parameters like pod length, pod shell thickness showed positive correlation (r = 0.77) with pod damage. Biochemical parameters like moisture content in pods, total sugars, reducing and non-reducing and protein content showed a positive correlation (r = 0.84, 0.86, 0.82, 0.89 and 0.79) with pod damage. Phenol content and fibre content in pods had a negative correlation (r = -0.93 and -0.89) with pod damage.
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Pierella Karlusich, Juan José, Chris Bowler et Haimanti Biswas. « Carbon Dioxide Concentration Mechanisms in Natural Populations of Marine Diatoms : Insights From Tara Oceans ». Frontiers in Plant Science 12 (30 avril 2021). http://dx.doi.org/10.3389/fpls.2021.657821.
Texte intégralRésumé :
Marine diatoms, the most successful photoautotrophs in the ocean, efficiently sequester a significant part of atmospheric CO2 to the ocean interior through their participation in the biological carbon pump. However, it is poorly understood how marine diatoms fix such a considerable amount of CO2, which is vital information toward modeling their response to future CO2 levels. The Tara Oceans expeditions generated molecular data coupled with in situ biogeochemical measurements across the main ocean regions, and thus provides a framework to compare diatom genetic and transcriptional flexibility under natural CO2 variability. The current study investigates the interlink between the environmental variability of CO2 and other physicochemical parameters with the gene and transcript copy numbers of five key enzymes of diatom CO2 concentration mechanisms (CCMs): Rubisco activase and carbonic anhydrase (CA) as part of the physical pathway, together with phosphoenolpyruvate carboxylase, phosphoenolpyruvate carboxykinase, and malic enzyme as part of the potential C4 biochemical pathway. Toward this aim, we mined >200 metagenomes and >220 metatranscriptomes generated from samples of the surface layer of 66 globally distributed sampling sites and corresponding to the four main size fractions in which diatoms can be found: 0.8–5 μm, 5–20 μm, 20–180 μm, and 180–2,000 μm. Our analyses revealed that the transcripts for the enzymes of the putative C4 biochemical CCM did not in general display co-occurring profiles. The transcripts for CAs were the most abundant, with an order of magnitude higher values than the other enzymes, thus implying the importance of physical CCMs in diatom natural communities. Among the different classes of this enzyme, the most prevalent was the recently characterized iota class. Consequently, very little information is available from natural diatom assemblages about the distribution of this class. Biogeographic distributions for all the enzymes show different abundance hotspots according to the size fraction, pointing to the influence of cell size and aggregation in CCMs. Environmental correlations showed a complex pattern of responses to CO2 levels, total phytoplankton biomass, temperature, and nutrient concentrations. In conclusion, we propose that biophysical CCMs are prevalent in natural diatom communities.
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Hellmich, Christian, Niketa Ukaj, Bart Smeets, Hans van Oosterwyck, Nenad Filipovic, Luis Zelaya-Lainez, Johannes Kalliauer et Stefan Scheiner. « Hierarchical Biomechanics : Concepts, Bone as Prominent Example, and Perspectives Beyond ». Applied Mechanics Reviews, 18 juillet 2022. http://dx.doi.org/10.1115/1.4055032.
Texte intégralRésumé :
Abstract Biological materials and systems are hierarchically organized.The main motivation for hierarchical biomechanics is that the wide variability of mechanical properties encountered at the macroscopic scale may be traced back to just a few universal. i.e. tissue-invariant, mechanical properties of elementary components at a sufficiently small scale (such as collagen, elastin, and water in case of soft tissues; complemented by hydroxyapatite in case of hard tissues), and to the nano and microstructures which the latter build up. This challenging task requires a physically rigorous and mathematically sound basis, as provided by Finite Element and Fast Fourier Transform methods, as well as by continuum micromechanics resting on (semi-)analytical solutions for Eshelby-type matrix-inclusion problems. Corresponding numerical and analytical mathematical models have undergone diligent experimental validation, by means of data stemming from a variety of biophysical, biochemical, and biomechanical testing methods, such as light and electron microscopy, ultrasonic testing and scanning acoustic microscopy, as well as physico-chemical tests associated with dehydration, demineralization, decollagenization, ashing, and weighing in air and fluid. While elastic scale transition and homogenization methods have attained a high maturity level, the hierarchical nature of dissipative (i.e. viscous or strength) properties is still a vibrant field of research. This applies even more to hierarchical approaches elucidating the interface between biological cells and extracellular matrices, and to the highly undiscovered mechanics unfolding within biological cells.
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« Comparison of High Range and Low Range of Sensor eAG and 24-Hour Daily GF Using 3+ years of Continuous Glucose Monitoring Sensor Device Collected Data Based on GH-Method : Math-Physical Medicine (No. 458) ». Advances in Bioengineering and Biomedical Science Research 4, no 3 (28 septembre 2022). http://dx.doi.org/10.33140/abbsr.04.03.003.
Texte intégralRésumé :
Since 5/5/2018, the author utilized a continuous glucose monitoring (CGM) sensor device to collect his glucoses 96 times each day. He then calculates his average daily sensor glucoses (eAG) and sensor glucose fluctuation (GF) within a 24-hour period each. His GF is defined as the maximum glucose value minus the minimum glucose value within a day. The definition of “eAG” is the mean value of glucose data that is similar to HbA1C which is useful in diabetes control. Moreover, the glucose excursion or GF has noticeable influences on various diabetes complications. During the period of 1,218 days from 5/5/2018 through 5/31/2021, he has collected a total of 116,928 glucose data. With this big data accumulated for over 3+ years and stored on a cloud server, it is easily for him to study and observe the overall glucose changes from day to day along with the phenomenon of his daily GF changes. During the past decade, the medical community has used the term “glycemic variability (GV)” to describe the glucose excursion which involves some questionable definitions of mathematical equations with less-quantitative and somewhat inconclusive findings. It is the author’s belief that the word “variability” could mean many things to different people; therefore, he decides to apply the basic concept of glucose excursion (fluctuation) without using the defined GV equation. This will allow him to have a better understanding and achieve a deeper appreciation for the important biophysical phenomenon of “glucose fluctuation”. Many research publications have covered the importance and impact of GV or GF on diabetic macro-vascular and microvascular complications (References 16 and 17). In those publications, it has defined and “qualitatively proven” that GF does impact the macro-vascular system, including the heart and brain, as well as the micro-vascular system such as kidneys, feet, eyes, nerves, etc. This particular report adopts the author’s developed GH-Method: math-physical medicine to seek more quantitatively described results. Hopefully, it can provide a different but still accurate enough description to complement those using biochemical medicine interpretations of glucose and glucose fluctuations.