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At least 1,477 records · Page 82
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Ecophysiology of mesophotic reef‐building corals in Hawai‘i is influenced by symbiont–host associations, photoacclimatization, trophic plasticity, and adaptation

Abstract Mesophotic reef corals remain largely unexplored in terms of the genetic adaptations and physiological mechanisms to acquire, allocate, and use energy for survival and reproduction. In the Hawaiian Archipelago, the Leptoseris species complex form the most spatially extensive mesophotic coral ecosystem known and provide habitat for a unique community. To study how the ecophysiology of Leptoseris species relates to symbiont–host specialization and understand the mechanisms responsible for coral energy acquisition in extreme low light environments, we examined Symbiodinium (endosymbiotic dinoflagellate) photobiological characteristics and the lipids and isotopic signatures from Symbiodinium and coral hosts over a depth‐dependent light gradient (55–7 μ mol photons m −2 s −1 , 60–132 m). Clear performance differences demonstrate different photoadaptation and photoacclimatization across this genus. Our results also show that flexibility in photoacclimatization depends primarily on Symbiodinium type. Colonies harboring Symbiodinium sp. COI‐2 showed significant increases in photosynthetic pigment content with increasing depth, whereas colonies harboring Symbiodinium spp. COI‐1 and COI‐3 showed variability in pigment composition, yield measurements for photosystem II, as well as size and density of Symbiodinium cells. Despite remarkable differences in photosynthetic adaptive strategies, there were no significant differences among lipids of Leptoseris species with depth. Finally, isotopic signatures of both host and Symbiodinium changed with depth, indicating that coral colonies acquired energy from different sources depending on depth. This study highlights the complexity in physiological adaptations within this symbiosis and the different strategies used by closely related mesophotic species to diversify energy acquisition and to successfully establish and compete in extreme light‐limited environments.

Padilla‐Gamiño, Jacqueline L.↗
DOE OSTI2016

Peptide backbone modification in the bend region of amyloid-β inhibits fibrillogenesis but not oligomer formation

Current evidence suggests that oligomers of the amyloid-β (Aβ) peptide are involved in the cellular toxicity of Alzheimer’s disease, yet their biophysical characterization remains difficult because of lack of experimental control over the aggregation process under relevant physiologic conditions. Here in this paper, we show that modification of the Aβ peptide backbone at Gly29 allows for the formation of oligomers but inhibits fibril formation at physiologic temperature and pH. Our results suggest that the putative bend region in Aβ is important for higher-order aggregate formation.

2-nitrobenzyl↗
DOE OSTI2023

Single-Filament Imaging Mass Spectrometry Lipidomics in Arthrospira platensis

Elucidating intra-organismal biochemical and lipid organization in photosynthetic biological cell factories of filamentous cyanobacteria, i.e., Arthrospira platensis (Spirulina), is important to track physiological response mechanisms during growth. Little is known about the filaments' biochemical organization and cellular structure and no label-free imaging techniques exist that provide molecular mapping. We applied ultra-high resolution mass spectrometry (7T FT-ICR-MS) matrix-assisted laser desorption ionization (MALDI) imaging to immobilized Spirulina filaments to investigate the localization of lipids across distinct physiological regions. We optimized matrix selection and deposition methods with the goal of facilitating high spatial, and intra-filament, resolution using untargeted multivariate statistical spectral deconvolution across MS pixels. Our results demonstrate an improved two step application with an optimized procedure for intra-organismal lipid profiling to improve analyte sensitivity and achieve higher spatial resolution, whereby we evaluate three conventional matrices 2,5-dihydroxybenzoic acid (DHB), a 9:1 ratio of DHB:superDHB (sDHB), 1,5- diaminonaphthalene (DAN) and a 50:50 mix of DHB:sDHB and compare delineation and pixel-based elucidation of intra-filament lipidomics. We identified a total of 1,626 features that could be putatively assigned a lipid-like formula based on database query and 46 unique features, with associated lipid assignments that were significantly distinct in their intra-filament location. MALDI- imaging MS with untargeted statistical spectral deconvolution was used to visualize intra-filament lipidomics organization in Spirulina filaments. Improvements in matrix deposition, including sequential sublimation and pneumatic spraying, increased signal abundance at high spatial resolution and allowed for identification of distinct lipid composition regions. Here in this work outlines a methodology that may be used for micro-ecological untargeted molecular phenotyping.

09 BIOMASS FUELS↗
DOE OSTI2017

Unfolded Protein Response in Arabidopsis

The unfolded protein response (UPR) is a highly regulated signaling pathway that is largely conserved across eukaryotes. It is essential for cell homeostasis under environmental and physiological conditions that perturb the protein folding in the endoplasmic reticulum (ER). Arabidopsis is one of the outstanding multicellular model systems in which to investigate the UPR. Here, we described a protocol to induce the UPR in plants, specifically arabidopsis, and to estimate their ability to cope with ER stress through the quantification of physiological parameters.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Plant Cell Vacuoles: Staining and Fluorescent Probes

In plant cells, vacuoles are extremely important for growth and development, and influence important cellular functions as photosynthesis, respiration, and transpiration. Plant cells contain lytic and storage vacuoles, whose size can be different depending on cell type and tissue developmental stage. One of the main roles of vacuoles is to regulate the cell turgor in response to different stimuli. Thus studying the morphology, dynamics and physiology of vacuole is fundamentally important to advance knowledge in plant cell biology at large. The availability of fluorescent probes allows marking vacuoles in multiple ways. These may be fast, when using commercially available chemical dyes, or relatively slow, in the case of specific genetically-encoded markers based on proteins directed either to the membrane of the vacuole (tonoplast) or to the vacuole lumen. Any of these approaches provides useful information about the morphology and physiology of the vacuole.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Environmental Constraints that Limit Methanogenesis

Methanogens are active in many different ecosystems, including habitats with biologically-derived organic matter as substrates such as aquatic sediments, wetlands, agricultural or natural soils subject to inundation, sewage digesters, and the anoxic portions of animal digestive tracts. Methanogens are also present in habitats with geochemically-supplied substrates such as hot springs, hydrothermal vents, volcanically-influenced habitats, and, potentially, the deep crustal subsurface. Methanogens as a group tolerate a broad range of physicochemical conditions, including temperatures from -2 to 122°C, pH values of 3.0 to 10.2, salinities up to halite saturation, and pressures of at least 75 MPa. Globally, variations in methane emissions can be explained to a large degree by variations in temperature and water availability. The distribution and activity of methanogens are constrained by ecological interactions that can be stimulatory or competitive, and by physicochemical factors that act at the biochemical or bioenergetic levels. In addition to the constraints placed on methanogens by physicochemical extremes, methanogen distribution and activity are constrained by the availability of energy and nutrients, the presence of inhibitory molecules (most notably oxygen), and the seawater anion, sulfate, due to competitive ecological interactions. Although methanogen tolerances to individual extremes are documented in culture, and the corresponding biochemical adaptations are understood to varying degrees, the natural environment frequently presents combinations of extreme conditions and energy limitations that may limit methanogen distribution to less than the optimally tolerated range of a single parameter. Little is understood about the compound effects of such extremes, nor the commonalities among them that will ultimately form the basis for predictive models of environmental methanogen population distribution. Future work that targets these questions, through a combination of culture work, “omic” analyses, in situ studies, and conceptual and quantitative models, will be needed to better understand the physiological ecology of methanogens.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Functional Anatomical Traits of the Photosynthetic Organs of Plants with Crassulacean Acid Metabolism

Crassulacean acid metabolism (CAM) is a photosynthetic adaptation to water and/or CO2 limited environments that has evolved in 400 genera from 36 families of higher plants. Despite the taxonomic and ecological diversity of CAM, plants with this photosynthetic specialization share a number of common anatomical traits that impinge on the physiological processes underpinning photosynthetic CO2 assimilation and water use. Thick, succulent leaves and/or stems are typical for terrestrial CAM plants. The large cells within these succulent tissues serve to accommodate the overnight vacuolar accumulation of malic acid that defines CAM and also increase water storage capacity. Significant morphological and anatomical diversity exists among leaf and stem succulents that impact on water-use strategies and thus the predisposition towards CAM. We provide an overview of CAM diversity in terms of leaf and stem anatomy, leaf venation and stomatal patterning. We consider the physiological implications of these anatomical traits in terms of water use and leaf hydraulic properties as well as the impacts on CO2 uptake and carbon gain. We also discuss which anatomical traits are likely to be important determinants for the mode and level of CAM that might be engineered into non-CAM species as a means of improving plant water use efficiency.

Borland, Anne M.↗
DOE OSTI2018

Regulatory Tools for Controlling Gene Expression in Cyanobacteria

Cyanobacteria are attractive hosts for converting carbon dioxide and sunlight into desirable chemical products. To engineer these organisms and manipulate their metabolic pathways, the biotechnology community has developed genetic tools to control gene expression. Many native cyanobacterial promoters and related sequence elements have been used to regulate genes of interest, and heterologous tools that use non-native small molecules to induce gene expression have been demonstrated. Overall, IPTG-based induction systems seem to be leaky and initially demonstrate small dynamic ranges in cyanobacteria. Consequently, a variety of other induction systems have been optimized to enable tighter control of gene expression. Tools require significant optimization because they function quite differently in cyanobacteria when compared to analogous use in model heterotrophs. We hypothesize that these differences are due to fundamental differences in physiology between organisms. This review is not intended to summarize all known products made in cyanobacteria nor the performance (titer, rate, yield) of individual strains, but instead will focus on the genetic tools and the inherent aspects of cellular physiology that influence gene expression in cyanobacteria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Gastrostomy Tube Placement Without Nasogastric Tube: A Retrospective Evaluation in 85 Patients

Purpose: Our study evaluated techniques for percutaneous gastrostomy (G)-tube placement without the use of a nasogastric (NG) tube. Instead, direct puncture of a physiologic air bubble or effervescent-enhanced gastric bubble distention was performed in patients with upper digestive tract obstruction (UDTO) or psychological objections to NG tubes. Materials and Methods: A total of 886 patients underwent G-tube placement in our department during a period of 7 years. We present our series of 85 (9.6%) consecutive patients who underwent percutaneous G-tube placement without use of an NG tube. Results: Of these 85 patients, fluoroscopic guided access was attempted by direct puncture of a physiologically present gastric air bubble in 24 (28%) cases. Puncture of an effervescent-induced large gastric air bubble was performed in 61 (72%) patients. Altogether, 82 (97%) of 85 G tubes were successfully placed in this fashion. The three failures comprised refusal of effervescent, vomiting of effervescent, and one initial tube misplacement when a deviation from our standard technique occurred. Conclusion: The described techniques compare favorably with published large series on G-tube placement with an NG tube in place. The techniques are especially suited for patients with UDTO due to head, neck, or esophageal malignancies, but they should be considered as an alternative in all patients. Direct puncture of effervescent-enhanced gastric bubble distention is a safe, patient-friendly and effective technique.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Respiratory-Induced Haemodynamic Changes: A Contributing Factor to IVC Filter Penetration

PurposeThe purpose of the study is to evaluate the influence of respiratory-induced vena caval hemodynamic changes on filter migration/penetration.Materials and MethodsAfter placement of either a Gunther Tulip or Celect IVC filter, 101 consecutive patients scheduled for filter retrieval were prospectively enrolled in this study. Pre-retrieval CT scans were used to assess filter complications and to calculate cross-sectional area in three locations: at level of filter strut fixation, 3 cm above and 3 cm below. A 3D finite element simulation was constructed on these data and direct IVC pressure was recorded during filter retrieval. Cross-sectional areas and pressures of the vena cava were measured during neutral breathing and in Valsalva maneuver and identified filter complications were recorded. A statistical analysis of these variables was then performed.ResultsDuring Valsalva maneuvers, a 60 % decrease of the IVC cross-sectional area and a fivefold increase in the IVC pressure were identified (p < 0.001). There was a statistically significant difference in the reduction of the cross-sectional area at the filter strut level (p < 0.001) in patient with filter penetration. Difficulty in filter retrieval was higher in penetrated or tilted filters (p < 0.001; p = 0.005). 3D computational models showed significant IVC deformation around the filter during Valsalva maneuver.ConclusionCaval morphology and hemodynamics are clearly affected by Valsalva maneuvers. A physiological reduction of IVC cross-sectional area is associated with higher risk of filter penetration, despite short dwell times. Physiologic data should be used to improve future filter designs to remain safely implanted over longer dwell times.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Hotter droughts alter resource allocation to chemical defenses in piñon pine

Abstract Heat and drought affect plant chemical defenses and thereby plant susceptibility to pests and pathogens. Monoterpenes are of particular importance for conifers as they play critical roles in defense against bark beetles. To date, work seeking to understand the impacts of heat and drought on monoterpenes has primarily focused on young potted seedlings, leaving it unclear how older age classes that are more vulnerable to bark beetles might respond to stress. Furthermore, we lack a clear picture of what carbon resources might be prioritized to support monoterpene synthesis under drought stress. To address this, we measured needle and woody tissue monoterpene concentrations and physiological variables simultaneously from mature piñon pines ( Pinus edulis ) from a unique temperature and drought manipulation field experiment. While heat had no effect on total monoterpene concentrations, trees under combined heat and drought stress exhibited ~ 85% and 35% increases in needle and woody tissue, respectively, over multiple years. Plant physiological variables like maximum photosynthesis each explained less than 10% of the variation in total monoterpenes for both tissue types while starch and glucose + fructose measured 1-month prior explained ~ 45% and 60% of the variation in woody tissue total monoterpene concentrations. Although total monoterpenes increased under combined stress, some key monoterpenes with known roles in bark beetle ecology decreased. These shifts may make trees more favorable for bark beetle attack rather than well defended, which one might conclude if only considering total monoterpene concentrations. Our results point to cumulative and synergistic effects of heat and drought that may reprioritize carbon allocation of specific non-structural carbohydrates toward defense.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Neutron scattering in photosynthesis research: recent advances and perspectives for testing crop plants

The photosynthetic performance of crop plants under a variety of environmental factors and stress conditions, at the fundamental level, depends largely on the organization and structural flexibility of thylakoid membranes. These highly organized membranes accommodate virtually all protein complexes and additional compounds carrying out the light reactions of photosynthesis. Most regulatory mechanisms fine-tuning the photosynthetic functions affect the organization of thylakoid membranes at different levels of the structural complexity. In order to monitor these reorganizations, non-invasive techniques are of special value. On the mesoscopic scale, small-angle neutron scattering (SANS) has been shown to deliver statistically and spatially averaged information on the periodic organization of the thylakoid membranes in vivo and/or, in isolated thylakoids, under physiologically relevant conditions, without fixation or staining. More importantly, SANS investigations have revealed rapid reversible reorganizations on the timescale of several seconds and minutes. In this paper, we give a short introduction into the basics of SANS technique, advantages and limitations, and briefly overview recent advances and potential applications of this technique in the physiology and biotechnology of crop plants. We also discuss future perspectives of neutron crystallography and different neutron scattering techniques, which are anticipated to become more accessible and of more use in photosynthesis research at new facilities with higher fluxes and innovative instrumentation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Incorporating leaf chlorophyll content into a two-leaf terrestrial biosphere model for estimating carbon and water fluxes at a forest site

Chlorophyll is the main light-harvesting pigment in leaves, facilitating photosynthesis and indicating the supply of nitrogen for photosynthetic enzymes. In this study, we explore the feasibility of integrating leaf chlorophyll content (Chl leaf ) into a Terrestrial Biosphere Model (TBM), as a proxy for the leaf maximum carboxylation rate at 25 °C (V$_{max}^{25}$), for the purpose of improving carbon and water flux estimation. Measurements of Chl leaf and V$_{max}^{25}$ were made in a deciduous forest stand at the Borden Forest Research Station in southern Ontario, Canada, where carbon and water fluxes were measured by the eddy covariance method. The use of Chl leaf -based V$_{max}^{25}$ in the TBM significantly reduces the bias of estimated gross primary productivity (GPP) and evapotranspiration (ET) and improves the temporal correlations between the simulated and the measured fluxes, relative to the commonly employed cases of using specified constant V$_{max}^{25}$, leaf area index (LAI)-based V$_{max}^{25}$ or specific leaf area (SLA)-based V$_{max}^{25}$. The biggest improvements are found in spring and fall, when the mean absolute errors (MAEs) between modelled and measured GPP are reduced from between 2.2–3.2 to 1.8 g C m -2 d -1 in spring and from between 2.1–2.8 to 1.8 g C m -2 d -1 in fall. The MAEs in ET estimates are reduced from 0.7–0.8 mm d -1 to 0.6 mm d -1 in spring, but no significant improvement is noted in autumn. A two-leaf upscaling scheme is used to account for the uneven distribution of incoming solar radiation inside canopies and the associated physiological differences between leaves. We found that modelled V$_{max}^{25}$ in sunlit leaves is 34% larger than in the shaded leaves of the same Chl leaf , which echoes previous physiological studies on light acclimation of plants. This study represents the first case of the incorporation of chlorophyll as a proxy for V$_{max}^{25}$ in a two-leaf TBM at a forest stand and demonstrates the efficacy of using chlorophyll to constrain V$_{max}^{25}$ and reduce the uncertainties in GPP and ET simulations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

An Unmanned Aerial System (UAS) for concurrent measurements of solar-induced chlorophyll fluorescence and hyperspectral reflectance toward improving crop monitoring

Unmanned aerial system (UAS)-based remote sensing can provide high spatial- and temporal-resolution crop monitoring for precision management. Existing crop monitoring UAS primarily use conventional techniques such as multi-spectral broadband vegetation indices (VIs) to track canopy structure/biomass. Recently developed lightweight hyperspectral sensors can track crop physiology and performance via complementary signals such as solar-induced chlorophyll fluorescence (SIF) and photochemical reflectance index (PRI) that can be derived from hyperspectral reflectance. However, few existing UAS can acquire high-quality SIF and hyperspectral reflectance. Here, we designed a novel UAS that simultaneously captures far-red SIF and hyperspectral reflectance, using a single bifurcated fiber and motorized arm to measure downwelling and upwelling irradiance. The UAS was tested over (1) a heterogeneous corn field with spatially varying crop yield potential and (2) a set of soybean and corn plots under differing nutrient treatments. Our UAS can maintain stability under low-to-moderate winds (2–3 m/s) with <0.4 m geolocation accuracy, <0.1 m altitude drift, and <1.5° error of the fiber optic from nadir position during scanning. Weekly seasonal campaigns reveal that SIF outperforms conventional VIs such as the normalized difference vegetation index (NDVI) for distinguishing plots with different crop yield potential, especially after canopy closure when NDVI tends to saturate. The UAS can capture the diurnal dynamics of SIF and PRI for both corn and soybean. At the seasonal scale, SIF acquired from the UAS correlates well with that from a fixed SIF tower system ( R 2 = 0.81), which measured the same target albeit with different footprints, demonstrating the capability of UAS in characterizing the seasonal progression of crop activity. In conclusion, our newly developed UAS provides high-quality SIF and hyperspectral reflectance, facilitating mechanistic understanding of the physiological control on photosynthesis dynamics. Our findings also imply that this UAS could enable extension of fixed tower-based systems to monitor multiple targets from diurnal to seasonal scales and improve monitoring of heterogeneous fields.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Selection-enriched genomic loci (SEGL) reveals genetic loci for environmental adaptation and photosynthetic productivity in Chlamydomonas reinhardtii

This work demonstrates an approach to produce and select hybrid algal strains exhibiting increased photosynthetic productivity under multiple environmental conditions. This simultaneously addresses two major impediments to improving algal bioenergy production: 1) generating new genetic variants with improved performance; and 2) disentangling complex interactions between genetic and physiological factors contributing to these improvements. We pooled progeny generated from mating two environmental isolates of the green alga Chlamydomonas reinhardtii and cultured the pools under multiple environmental conditions. Strains from the outcompeting populations showed substantial (in some cases over 3 fold) increases in productivity over the parental lines under certain environments related to biomass production, including laboratory conditions as well as hyperoxia, fluctuating light, high salinity and high temperature. The results indicate that C. reinhardtii has remarkable, untapped, directed evolution capacity that may be harnessed using breeding and competition approaches. The populations were deep sequenced at multiple time points to identify “Selection-Enriched Genomic Loci” (SEGL) that accumulated in the populations, and thus likely confer increased fitness under the respective environmental conditions. With improved resolution, SEGL mapping can identify allelic combinations used for targeted breeding approaches, generating elite algal lines with multiple desirable traits, as well as to further understand the genetic and mechanistic bases of photosynthetic productivity. Increasing the photosynthetic efficiency of algae during biomass production is perhaps the most critical hurdle for economically sustainable algal based biofuels. This presents unique challenges because modifications designed to increase photosynthesis often result in decreased fitness, due to production of toxic reactive oxygen species when photosynthesis is not adequately regulated. These problems are exacerbated under natural and outdoor production environments because of the complex nature of photosynthesis and the multifaceted interactions between genetic, environmental and physiological factors. Here, we demonstrate a high throughput biotechnological screening approach that simultaneously produces algal strains with highly increased autotrophic productivity and identifies genomic loci contributing to these improvements. Our results demonstrate that Chlamydomonas reinhardtii exhibits high directed evolutionary capacity readily accessed through breeding and selection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Knockdown of pre-mRNA cleavage factor Im 25 kDa promotes neurite outgrowth

Highlights: Black-Right-Pointing-Pointer CFIm25 knockdown promoted NGF-induced neurite out growth from PC12 cells. Black-Right-Pointing-Pointer Depletion of CFIm25 did not influence the morphology of proliferating PC12 cells. Black-Right-Pointing-Pointer CFIm regulated NGF-induced neurite outgrowth via coordinating RhoA activity. Black-Right-Pointing-Pointer CFIm25 knockdown increase the number of primary dendrites of hippocampal neurons. -- Abstract: Mammalian precursor mRNA (pre-mRNA) cleavage factor I (CFIm) plays important roles in the selection of poly(A) sites in a 3 Prime -untranslated region (3 Prime -UTR), producing mRNAs with variable 3 Prime ends. Because 3 Prime -UTRs often contain cis elements that impact stability or localization of mRNA or translation, alternative polyadenylation diversifies utilization of primary transcripts in mammalian cells. However, the physiological role of CFIm remains unclear. CFIm acts as a heterodimer comprising a 25 kDa subunit (CFIm25) and one of the three large subunits-CFIm59, CFIm68, or CFIm72. CFIm25 binds directly to RNA and introduces and anchors the larger subunit. To examine the physiological roles of CFIm, we knocked down the CFIm25 gene in neuronal cells using RNA interference. Knockdown of CFIm25 increased the number of primary dendrites of developing hippocampal neurons and promoted nerve growth factor (NGF)-induced neurite extension from rat pheochromocytoma PC12 cells without affecting the morphology of proliferating PC12 cells. On the other hand, CFIm25 knockdown did not influence constitutively active or dominantly negative RhoA suppression or promotion of NGF-induced neurite extension from PC12 cells, respectively. Taken together, our results indicate that endogenous CFIm may promote neuritogenesis in developing neurons by coordinating events upstream of NGF-induced RhoA inactivation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Molecular mechanisms of the plant heat stress response

Highlights: ► This review elaborates the response networks of heat stress in plants. ► It elaborates proteins responding to heat stress in special physiological period. ► The proteins and pathways have formed a basic network of the heat stress response. ► Achievements of the various technologies are also combined. -- Abstract: High temperature has become a global concern, which seriously affects the growth and production of plants, particularly crops. Thus, the molecular mechanism of the heat stress response and breeding of heat-tolerant plants is necessary to protect food production and ensure crop safety. This review elaborates on the response networks of heat stress in plants, including the Hsf and Hsp response pathways, the response of ROS and the network of the hormones. In addition, the production of heat stress response elements during particular physiological periods of the plant is described. We also discuss the existing problems and future prospects concerning the molecular mechanisms of the heat stress response in plants.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation. We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.

60 APPLIED LIFE SCIENCES↗