Toxicological effects of nanoparticles in plants: Mechanisms involved at morphological, physiological, biochemical and molecular levels.

The rapid advancement of nanotechnology has led to unprecedented innovations across diverse industries, including pharmaceuticals, agriculture, cosmetics, electronics, textiles, and food, owing to the unique properties of nanoparticles. The extensive production and unregulated release of synthetic nanoparticles may contribute to nanopollution within the ecosystem. In the agricultural sector, nanotechnology is increasingly utilized to improve plant productivity, enhance resistance to stressors, and reduce the usage of chemicals. However, the uncontrolled discharge of nanoparticles into the natural environment raises concerns regarding possible plant toxicological impacts. The review focuses on the translocation of these particles within the plants, emphasizing their phytotoxicological effects at morphological, physiological, biochemical, and molecular levels. Eventhough the beneficial aspects of these nanoparticles are evident, excessive usage of nanoparticles at higher concentrations may lead to potential adverse effects. The phytotoxicity resulting from excessive amounts of nanoparticles affects seed germination and biomass production, disrupts the photosynthesis system, induces oxidative stress, impacts cell membrane integrity, alters gene expression, causes DNA damage, and leads to epigenetic variations in plants. Nanoparticles are found to directly associate with the cell membrane and cell organelles, leading to the dissolution and release of toxic ions, generation of reactive oxygen species (ROS) and subsequent oxidative stress. The present study signifies and accumulates knowledge regarding the application of nanoparticles in agriculture and illustrates a clear picture of their possible impacts on plants and soil microbes, thereby paving the way for future developments in nano-agrotechnology. The review concludes by addressing current challenges and proposing future directions to comprehend and mitigate the possible biological risks associated with nanoparticles in agriculture.

Fungal Endophytes as Mitigators against Biotic and Abiotic Stresses in Crop Plants.

The escalating global food demand driven by a gradually expanding human population necessitates strategies to improve agricultural productivity favorably and mitigate crop yield loss caused by various stressors (biotic and abiotic). Biotic stresses are caused by phytopathogens, pests, and nematodes, along with abiotic stresses like salt, heat, drought, and heavy metals, which pose serious risks to food security and agricultural productivity. Presently, the traditional methods relying on synthetic chemicals have led to ecological damage through unintended impacts on non-target organisms and the emergence of microbes that are resistant to them. Therefore, addressing these challenges is essential for economic, environmental, and public health concerns. The present review supports sustainable alternatives, emphasizing the possible application of fungal endophytes as innovative and eco-friendly tools in plant stress management. Fungal endophytes demonstrate capabilities for managing plants against biotic and abiotic stresses via the direct or indirect enhancement of plants' innate immunity. Moreover, they contribute to elevated photosynthesis rates, stimulate plant growth, facilitate nutrient mineralization, and produce bioactive compounds, hormones, and enzymes, ultimately improving overall productivity and plant stress resistance. In conclusion, harnessing the potentiality of fungal endophytes represents a promising approach toward the sustainability of agricultural practices, offering effective alternative solutions to reduce reliance on chemical treatments and address the challenges posed by biotic and abiotic stresses. This approach ensures long-term food security and promotes environmental health and economic viability in agriculture.

Zinc oxide nanoparticles prepared through microbial mediated synthesis for therapeutic applications: a possible alternative for plants.

Zinc oxide nanoparticles (ZnO-NPs) synthesized through biogenic methods have gained significant attention due to their unique properties and potential applications in various biological fields. Unlike chemical and physical approaches that may lead to environmental pollution, biogenic synthesis offers a greener alternative, minimizing hazardous environmental impacts. During biogenic synthesis, metabolites present in the biotic sources (like plants and microbes) serve as bio-reductants and bio-stabilizers. Among the biotic sources, microbes have emerged as a promising option for ZnO-NPs synthesis due to their numerous advantages, such as being environmentally friendly, non-toxic, biodegradable, and biocompatible. Various microbes like bacteria, actinomycetes, fungi, and yeast can be employed to synthesize ZnO-NPs. The synthesis can occur either intracellularly, within the microbial cells, or extracellularly, using proteins, enzymes, and other biomolecules secreted by the microbes. The main key advantage of biogenic synthesis is manipulating the reaction conditions to optimize the preferred shape and size of the ZnO-NPs. This control over the synthesis process allows tailoring the NPs for specific applications in various fields, including medicine, agriculture, environmental remediation, and more. Some potential applications include drug delivery systems, antibacterial agents, bioimaging, biosensors, and nano-fertilizers for improved crop growth. While the green synthesis of ZnO-NPs through microbes offers numerous benefits, it is essential to assess their toxicological effects, a critical aspect that requires thorough investigation to ensure their safe use in various applications. Overall, the presented review highlights the mechanism of biogenic synthesis of ZnO-NPs using microbes and their exploration of potential applications while emphasizing the importance of studying their toxicological effects to ensure a viable and environmentally friendly green strategy.

Competent antioxidant and antiglycation properties of zinc oxide nanoparticles (ZnO-NPs) phyto-fabricated from aqueous leaf extract of Boerhaavia erecta L.

During the present century, plant-based zinc oxide nanoparticles (ZnO-NPs) are exploited extensively for their vast biological properties due to their unique characteristic features and eco-friendly nature. Diabetes is one of the fast-growing human diseases/abnormalities worldwide, and the need for new/ novel antiglycation products is the need of the hour. The study deals with the phyto-fabrication of ZnO-NPs from Boerhaavia erecta, a medicinally important plant, and to evaluate their antioxidant and antiglycation ability in vitro. UV-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) were used to characterize the phyto-fabricated ZnO-NPs. The characterization of nanoparticles revealed that the particles showed an absorption peak at 362 nm and band gap energy of 3.2 eV, approximately 20.55 nm in size, with a ZnO elemental purity of 96.61%. The synthesized particles were found agglomerated when observed under SEM, and the FT-IR studies proved that the phyto-constituents of the extract involved during the different stages (reduction, capping, and stabilization) of nanoparticles synthesis. The antioxidant and metal chelating activities confirmed that ZnO-NPs could inhibit the free radicals generated, which was dose-dependent with an IC50 value between 1.81 and 1.94 mg mL-1, respectively. In addition, the phyto-fabricated nanoparticles blocked the formation of advanced glycation end products (AGEs) as noticed through inhibition of Amadori products, trapping of reactive dicarbonyl intermediate and breaking the cross-link of glycated protein. It was also noted that the phyto-fabricated ZnO-NPs significantly prevented the damage of red blood corpuscles (RBCs) induced by MGO. The present study's findings will provide an experimental basis for exploring ZnO-NPs in diabetes-related complications.

Insight into Recent Progress and Perspectives in Improvement of Antioxidant Machinery upon PGPR Augmentation in Plants under Drought Stress: A Review.

Agriculture has a lot of responsibility as the rise in the world's population demands more food requirements. However, more than one type of biotic and abiotic stress continually impacts agricultural productivity. Drought stress is a major abiotic stress that significantly affects agricultural productivity every year as the plants undergo several morphological, biochemical, and physiological modifications, such as repressed root and shoot growth, reduced photosynthesis and transpiration rate, excessive production of reactive oxygen species (ROS), osmotic adjustments, and modified leaf senescence regulating and stress signaling pathways. Such modifications may permanently damage the plants; therefore, mitigation strategies must be developed. The use of drought resistant crop cultivars is more expensive and labor-intensive with few advantages. However, exploiting plant growth promoting rhizobacteria (PGPR) is a proven alternative with numerous direct and indirect advantages. The PGPR confers induced systemic tolerance (IST) mechanisms in plants in response to drought stress via multiple mechanisms, including the alteration of root architecture, maintenance of high relative water content, improvement of photosynthesis rate, production of phytohormones, exopolysaccharides, ACC deaminase, carotenoids and volatiles, induction of antioxidant defense system, and alteration in stress-responsive gene expression. The commercial application of PGPR as bioinoculants or biostimulants will remain contingent on more robust strain selection and performance under unfavorable environmental conditions. This review highlights the possible mechanisms of PGPR by activating the plant adaptive defense systems for enhancing drought tolerance and improving overall growth and yield.

Mechanical conflict caused by a cell-wall-loosening enzyme activates de novo shoot regeneration.

Cellular heterogeneity is a hallmark of multicellular organisms. During shoot regeneration from undifferentiated callus, only a select few cells, called progenitors, develop into shoot. How these cells are selected and what governs their subsequent progression to a patterned organ system is unknown. Using Arabidopsis thaliana, we show that it is not just the abundance of stem cell regulators but rather the localization pattern of polarity proteins that predicts the progenitor's fate. A shoot-promoting factor, CUC2, activated the expression of the cell-wall-loosening enzyme, XTH9, solely in a shell of cells surrounding the progenitor, causing different mechanical stresses in these cells. This mechanical conflict then activates cell polarity in progenitors to promote meristem formation. Interestingly, genetic or physical perturbations to cells surrounding the progenitor impaired the progenitor and vice versa. These suggest a feedback loop between progenitors and their neighbors for shoot regeneration in the absence of tissue-patterning cues.

Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality and morbidity rate worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus, but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. OBJECTIVE: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of potential compounds. METHODS: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. RESULTS: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/mol. Among them, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-Dgalactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues, bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. CONCLUSION: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.

Fate, bioaccumulation and toxicity of engineered nanomaterials in plants: Current challenges and future prospects.

The main focus of this review is to discuss the current advancement in nano-metallic caused phytotoxicity on living organisms and current challenges in crops. Nanostructured materials provide new tools in agriculture to boost sustainable food production, but the main concern is that large-scale production and release of nanomaterials (NMs) into the ecosystem is a rising threat to the surrounding environment that is an urgent challenge to be addressed. The usage of NMs directly influences the transport pathways within plants, which directly relates to their stimulatory/ inhibitory effects. Because of the unregulated nanoparticles (NMs) exposure to soil, they are adsorbed at the root surface, followed by uptake and inter/intracellular mobility within the plant tissue, while the aerial exposure is taken up by foliage, mostly through cuticles, hydathodes, stigma, stomata, and trichomes, but the actual mode of NMs absorption into plants is still unclear. NMs-plant interactions may have stimulatory or inhibitory effects throughout their life cycle depending on their composition, size, concentration, and plant species. Although many publications on NMs interactions with plants have been reported, the knowledge on their uptake, translocation, and bioaccumulation is still a question to be addressed by the scientific community. One of the critical aspects that must be discovered and understood is detecting NMs in soil and the uptake mechanism in plants. Therefore, the nanopollution in plants has yet to be completely understood regarding its impact on plant health, making it yet another artificial environmental influence of unknown long-term consequences. The present review summarizes the uptake, translocation, and bioaccumulation of NMs in plants, focusing on their inhibitory effects and mechanisms involved within plants.

Induction of drought tolerance in Pennisetum glaucum by ACC deaminase producing PGPR- Bacillus amyloliquefaciens through Antioxidant defense system.

Rhizobacteria from pearl millet were screened to produce 1-aminocyclopropane-1-carboxylate (ACC) deaminase and to evaluate its role in alleviating drought stress. Amongst 96 isolates, 28 were positive for ACC deaminase production, with MMR04 offering maximum activity of 2196.23 nmol of α-ketobutyrate produced mg-1 of protein h-1. The ACC deaminase producing rhizobacteria with multiple beneficial properties along with root colonization and non-pathogenic were selected [Bacillus amyloliquefaciens (MMR04), Bacillus subtilis (MMR18) and Stenotrophomonas maltophilia (MMR36)] to confirm the presence of ACC deaminase gene. A significant enhancement in seed germination (91.75%) and seedling vigor (1213.73) was noted upon seed treatment with MMR04 and hence further evaluated for its ability to induce drought stress. The seed treatment with MMR04 improved plant growth parameters and total chlorophyll and RWC in plants grown under severe drought stress (G5) conditions compared to control plants. In addition, MMR04 seed treatment enhanced proline, APX and SOD activity while decreased the MDA content up to 2.3 fold compared to untreated plants (G5). Gene expression studies revealed a significant decrease of 3.3 and 1.8 fold in the relative expression of drought-responsive (DREB-1E) and ethylene-responsive factor (ERF-1B) marker genes, respectively and an increase of 2.2 and 2.9 fold in the relative expression of APX1 and SOD1, respectively in MMR04 treated plants grown under G5 conditions over control. The results confirmed that ACC deaminase producing B. amyloliquefaciens MMR04 could defend the pearl millet plants against drought stress through an antioxidative system, thereby warranting its application in drought stress management.

Plant-Mediated Zinc Oxide Nanoparticles: Advances in the New Millennium towards Understanding Their Therapeutic Role in Biomedical Applications.

Zinc oxide nanoparticles have become one of the most popular metal oxide nanoparticles and recently emerged as a promising potential candidate in the fields of optical, electrical, food packaging, and biomedical applications due to their biocompatibility, low toxicity, and low cost. They have a role in cell apoptosis, as they trigger excessive reactive oxygen species (ROS) formation and release zinc ions (Zn2+) that induce cell death. The zinc oxide nanoparticles synthesized using the plant extracts appear to be simple, safer, sustainable, and more environmentally friendly compared to the physical and chemical routes. These biosynthesized nanoparticles possess strong biological activities and are in use for various biological applications in several industries. Initially, the present review discusses the synthesis and recent advances of zinc oxide nanoparticles from plant sources (such as leaves, stems, bark, roots, rhizomes, fruits, flowers, and seeds) and their biomedical applications (such as antimicrobial, antioxidant, antidiabetic, anticancer, anti-inflammatory, photocatalytic, wound healing, and drug delivery), followed by their mechanisms of action involved in detail. This review also covers the drug delivery application of plant-mediated zinc oxide nanoparticles, focusing on the drug-loading mechanism, stimuli-responsive controlled release, and therapeutic effect. Finally, the future direction of these synthesized zinc oxide nanoparticles' research and applications are discussed.

Age, Wound Size, and Position of Injury - Dependent Vascular Regeneration Assay in Growing Leaves.

Recurring damage to the aerial organs of plants necessitates their prompt repair, particularly their vasculature. While vascular regeneration assays for aerial plant parts such as the stem and inflorescence stalk are well established, those for leaf vasculature remain unexplored. Recently, we established a new vascular regeneration assay in growing leaves and discovered the underlying molecular mechanism. Here, we describe the detailed stepwise method for the incision and regeneration assay used to study leaf vascular regeneration. By using a combination of micro-surgical perturbations, brightfield microscopy, and other experimental approaches, we further show that the age of the leaf as well as the position and size of the injury determine the overall success rate of regeneration. This easy-to-master vascular regeneration assay is an efficient and rapid method to study the mechanism of vascular regeneration in growing leaves. The assay can be readily combined with cellular and molecular biology techniques.

Bioprospecting of Rhizosphere-Resident Fungi: Their Role and Importance in Sustainable Agriculture.

Rhizosphere-resident fungi that are helpful to plants are generally termed as 'plant growth promoting fungi' (PGPF). These fungi are one of the chief sources of the biotic inducers known to give their host plants numerous advantages, and they play a vital role in sustainable agriculture. Today's biggest challenge is to satisfy the rising demand for crop protection and crop yield without harming the natural ecosystem. Nowadays, PGPF has become an eco-friendly way to improve crop yield by enhancing seed germination, shoot and root growth, chlorophyll production, and fruit yield, etc., either directly or indirectly. The mode of action of these PGPF includes the solubilization and mineralization of the essential micro- and macronutrients needed by plants to regulate the balance for various plant processes. PGPF produce defense-related enzymes, defensive/volatile compounds, and phytohormones that control pathogenic microbes' growth, thereby assisting the plants in facing various biotic and abiotic stresses. Therefore, this review presents a holistic view of PGPF as efficient natural biofertilizers to improve crop plants' growth and resistance.

Genotoxic and Cytotoxic Properties of Zinc Oxide Nanoparticles Phyto-Fabricated from the Obscure Morning Glory Plant Ipomoea obscura (L.) Ker Gawl.

The study was undertaken to investigate the antioxidant, genotoxic, and cytotoxic potentialities of phyto-fabricated zinc oxide nanoparticles (ZnO-NPs) from Ipomoea obscura (L.) Ker Gawl. aqueous leaf extract. The UV-visible spectral analysis of the ZnO-NPs showed an absorption peak at 304 nm with a bandgap energy of 3.54 eV, which are characteristics of zinc nanoparticles. Moreover, the particles were of nano-size (~24.26 nm) with 88.11% purity and were agglomerated as observed through Scanning Electron Microscopy (SEM). The phyto-fabricated ZnO-NPs offered radical scavenging activity (RSA) in a dose-dependent manner with an IC50 of 0.45 mg mL-1. In addition, the genotoxicity studies of ZnO-NPs carried out on onion root tips revealed that the particles were able to significantly inhibit the cell division at the mitotic stage with a mitotic index of 39.49%. Further, the cytotoxic studies on HT-29 cells showed that the phyto-fabricated ZnO-NPs could arrest the cell division as early as in the G0/G1 phase (with 92.14%) with 73.14% cells showing early apoptotic symptoms after 24 h of incubation. The results of the study affirm the ability of phyto-fabricated ZnO-NPs from aqueous leaf extract of I. obscura is beneficial in the cytotoxic application.

A coherent feed-forward loop drives vascular regeneration in damaged aerial organs of plants growing in a normal developmental context.

Aerial organs of plants, being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaves and stems to study the reunion between mechanically disconnected tissues. We show that PLETHORA (PLT) and AINTEGUMENTA (ANT) genes, which encode stem cell-promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. PLT proteins and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed-forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT-mediated regeneration response, leaf ground tissue cells can neither acquire the early vascular identity marker ATHB8, nor properly polarise auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaves. We reveal the mechanisms of vascular regeneration in plants and distinguish between the wound-repair ability of the tissue and its formation during normal development.

Induction of drought tolerance in tomato upon the application of ACC deaminase producing plant growth promoting rhizobacterium Bacillus subtilis Rhizo SF 48.

A total of ten 1-aminocyclopropane-1-carboxylate (ACC) deaminase producing PGPR isolates were selected and evaluated for the induction of drought stress tolerance in tomato. Among the selected PGPR, maximum seed (laboratory) and plant growth promotion (greenhouse) was observed in tomato seeds bacterized with Bacillus subtilis Rhizo SF 48. The genomic study confirmed the presence of ACC deaminase gene in Rhizo SF 48 and the obtained sequence was deposited to the NCBI database with the Accession No. MK652706. The tomato plants grown upon treatment with Rhizo SF 48 significantly enhanced plant growth even after exposing to different levels of drought stress as compared to stress induced control plants. About 7.5% and 38% increase in RWC were observed in Rhizo SF 48 treated tomato plants grown under well-watered and stress conditions (S4) compared to their control plants, respectively. An increase of 0.76, 0.23 and 0.78 fold in proline, SOD and APX activity and a decrease of 0.3 fold in MDA and H2O2 contents were observed in Rhizo SF 48 treated plants compared to control plants grown under S4 conditions. The histo-chemical studies showed lower accumulations of H2O2 and superoxide anion in the leaves of Rhizo SF 48 treated plants under drought stress, which was in confirmation with the quantification results of H2O2 and SOD. The qRT-PCR studies on drought (Le25) and ethylene responsive factor (SlERF84) marker genes showed that a significant decrease of 0.75 and 0.81 folds, respectively in Le25 and SlERF84 accumulation was observed in Rhizo SF 48 treated plants compared to untreated plants grown under S4 conditions. From the results, it can be attributed that ACC deaminase producing Rhizo SF 48 was able to protect tomato plants against oxidative damage caused due to drought stress and enhanced plant growth promotion. It can be concluded that ACC deaminase producing Rhizo SF 48 can serve as a useful bio-inoculant for sustainable tomato production in arid and semi-arid regions with water deficit.

Regrowing the damaged or lost body parts.

Plants display extraordinary ability to revive tissues and organs lost or damaged in injury. This is evident from the root tip restoration and classical experiments in stem demonstrating re-establishment of vascular continuity. While recent studies have begun to unravel the mechanistic understanding of tissue restoration in response to injury in underground plant organs, the molecular mechanisms of the same in aerial organs remain to be ventured deeper. Here, we discuss the possibility of unearthing the regulatory mechanism that can confer universal regeneration potential to plant body and further provide a comprehensive understanding of how tissue and organ regeneration gets triggered in response to mechanical injury and later gets terminated after re-patterning and regaining the appropriate size.

Transcriptome analysis of IFM-specific actin and myosin nulls in Drosophila melanogaster unravels lesion-specific expression blueprints across muscle mutations.

Muscle contraction is a highly fine-tuned process that requires the precise and timely construction of large protein sub-assemblies to form sarcomeres. Mutations in many genes encoding constituent proteins of this macromolecular machine result in defective functioning of the muscle tissue. However, the pathways underlying muscle degeneration, and manifestation of myopathy phenotypes are not well understood. In this study, we explored transcriptional alterations that ensue from the absence of the two major muscle proteins - myosin and actin - using the Drosophila indirect flight muscles. Our aim was to understand how the muscle tissue responds as a whole to the absence of either of the major scaffold proteins, whether the responses are generic to the tissue; or unique to the thick versus thin filament systems. Our results indicated that muscles respond by altering gene transcriptional levels in multiple systems active in muscle remodelling, protein degradation and heat shock responses. However, there were some responses that were filament-specific signatures of muscle degeneration, like immune responses, metabolic alterations and alterations in expression of muscle structural genes and mitochondrial ribosomal genes. These general and filament-specific changes in gene expression may be of relevance to human myopathies.

De novo assembly of plant body plan: a step ahead of Deadpool.

While in the movie Deadpool it is possible for a human to recreate an arm from scratch, in reality plants can even surpass that. Not only can they regenerate lost parts, but also the whole plant body can be reborn from a few existing cells. Despite the decades old realization that plant cells possess the ability to regenerate a complete shoot and root system, it is only now that the underlying mechanisms are being unraveled. De novo plant regeneration involves the initiation of regenerative mass, acquisition of the pluripotent state, reconstitution of stem cells and assembly of regulatory interactions. Recent studies have furthered our understanding on the making of a complete plant system in the absence of embryonic positional cues. We review the recent studies probing the molecular mechanisms of de novo plant regeneration in response to external inductive cues and our current knowledge of direct reprogramming of root to shoot and vice versa. We further discuss how de novo regeneration can be exploited to meet the demands of green culture industries and to serve as a general model to address the fundamental questions of regeneration across the plant kingdom.

Complement Biomarkers as Predictors of Disease Progression in Alzheimer's Disease.

There is a critical unmet need for reliable markers of disease and disease course in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The growing appreciation of the importance of inflammation in early AD has focused attention on inflammatory biomarkers in cerebrospinal fluid or plasma; however, non-specific inflammation markers have disappointed to date. We have adopted a targeted approach, centered on an inflammatory pathway already implicated in the disease. Complement, a core system in innate immune defense and potent driver of inflammation, has been implicated in pathogenesis of AD based on a confluence of genetic, histochemical, and model data. Numerous studies have suggested that measurement of individual complement proteins or activation products in cerebrospinal fluid or plasma is useful in diagnosis, prediction, or stratification, but few have been replicated. Here we apply a novel multiplex assay to measure five complement proteins and four activation products in plasma from donors with MCI, AD, and controls. Only one complement analyte, clusterin, differed significantly between control and AD plasma (controls, 295 mg/l; AD, 388 mg/l: p < 10- 5). A model combining clusterin with relevant co-variables was highly predictive of disease. Three analytes (clusterin, factor I, terminal complement complex) were significantly different between MCI individuals who had converted to dementia one year later compared to non-converters; a model combining these three analytes with informative co-variables was highly predictive of conversion. The data confirm the relevance of complement biomarkers in MCI and AD and build the case for using multi-parameter models for disease prediction and stratification.