Extreme Diversity Research Articles

Abstract 1208: Comparative analysis between DNA vs RNA-based T cell repertoire profiling for cancer immunotherapy

Abstract The T cell receptor (TCR), a defining structure of T cells is responsible for the recognition of the antigen-major histocompatibility complex, leading to the initiation of an immune response. The extreme diversity of the TCR repertoire represents a major analytical challenge. Massively parallel high throughput sequencing is commonly deployed to characterize various key features of T cell receptors including their clonal expansion and repertoire diversity. Genomic DNA is the most widely employed starting material to characterize the TCR repertoire. DNA is highly stable and contains a fixed copy number per cell, which allows for better quantification of TCR clones. However, the inclusiveness is a major limitation of using genomic DNA along with the PCR amplification challenges and sequencing errors due to recombined gene segments within the context of ‘unused’ segments and introns. Here we deploy RNA-based TCR profiling as an alternate strategy to overcome the major limitations associated with the DNA-based approach. Employing RNA with a simplified PCR amplification strategy allows a more comprehensive identification of unique TCR variants with greater sensitivity. It also provides information about expression levels of TCR sequences, and more importantly, excludes the non-productive sequences that are functionally irrelevant. In addition, Unique Molecular Indexing (UMIs) enables the determination of the absolute count of RNA transcripts processed in a sample, allowing straightforward error corrections. Citation Format: Shanker Kalyana-Sundaram, Christopher Traini, Wendy Halsey, Heather Jackson, Sabyasachi Bhattacharya, Niranjan Yanamandra, Ganesh Sathe, George Livi. Comparative analysis between DNA vs RNA-based T cell repertoire profiling for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1208.

The Huckleberry Ridge Tuff, Yellowstone: evacuation of multiple magmatic systems in a complex episodic eruption

AbstractThe 2·08 Ma, ∼2500 km3 Huckleberry Ridge Tuff (HRT) eruption, Yellowstone, generated two fall deposits and three ignimbrite members (A, B, C), accompanying a ∼95 x 65 km caldera collapse. Field data imply that the pre-A fall deposits took weeks to be erupted, then breaks of weeks to months occurred between members A and B, and years to decades between B and C. We present compositional and isotopic data from single silicic clasts (pumice or fiamme) in the three ignimbrite members, plus new data from co-eruptive mafic components to reconstruct the nature and evacuation history of the HRT crustal magmatic complex. Geochemical data, building on field characteristics, are used to group nine silicic clast types into seven compositional suites (A1-A3; B1; C1-C3) within their respective members A, B and C. Isotopic data are then added to define four magmatic systems that were tapped simultaneously and/or sequentially during the eruption. Systems 1 and 2 fed the initial fall deposits and then vented throughout member A, accompanied by trace amounts of mafic magma. In member A, volumetrically dominant system 1 is represented by a rhyolite suite (A1: 73·0–77·7 wt % SiO2, 450–1680 ppm Ba) plus a distinct low-silica rhyolite suite (A2: 69·2–71·6 wt % SiO2, >2500 ppm Ba). System 2 yielded only a low-Ba, high-silica rhyolite suite (A3: 76·7–77·4 wt % SiO2, ≤250 ppm Ba). Glass compositions in pumices from systems 1 and 2 show clustering, indicative of the same multiple melt-dominant bodies identified in the initial fall deposits and earliest ignimbrite. Member B samples define suite B1 (70·7–77·4 wt % SiO2, 540–3040 ppm Ba) derived from magmatic system 1 (but not 2) that had undergone mixing and reorganisation during the A: B time break, accompanying mafic magma inputs. Mafic scoriae erupted in upper member B cover similar compositions to the member A clasts, but extend over a much broader compositional range. Member C clast compositions reflect major changes during the B: C time break, including rejuvenation of magmatic system 2 (last seen in member A) as suite C3 (75·3–77·2 wt % SiO2, 100–410 ppm Ba), plus the appearance of two new suites with strong crustal signatures. Suite C2 is another rhyolite (74·7–77·6 wt % SiO2, with Ba decreasing with silica from 2840 to 470 ppm) that defines magmatic system 3. Suite C2 also shows clustered glass compositions, suggesting that multiple melt-dominant bodies were a repetitive feature of the HRT magmatic complex. Suite C1, in contrast, is dacite to rhyolite (65·6–75·0 wt % SiO2, with Ba increasing with silica from 750 to 1710 ppm) that defines magmatic system 4. Compositions from magmatic systems 1 and 2 dominantly reflect fractional crystallization, but include partial melting of cumulates related to earlier intrusions of the same mafic magmas as those syn-eruptively vented. Country rock assimilation was limited to minor amounts of a more radiogenic (with respect to Sr) evolved contaminant. In contrast, systems 3 and 4 show similar strongly crustal isotopic compositions (despite their differences in elemental composition) consistent with assimilation of Archean rocks via partial melts derived from cumulates associated with contrasting mafic lineages. System 3 links to the same HRT mafic compositions co-erupted in members A and B. In contrast, system 4 links to olivine tholeiite compositions erupted in the Yellowstone area before, sparsely during, and following the HRT itself. All four magmatic systems were housed beneath the HRT caldera area. Systems 1 and 2 were hosted in Archean crust that had been modified by Cretaceous/Eocene magmatism, whereas systems 3 and 4 were hosted within crust that retained Archean isotopic characteristics. The extreme compositional diversity in the HRT highlights the spatial and temporal complexities that can be associated with large-volume silicic magmatism.

Excision and transfer of an integrating and conjugative element in a bacterial species with high recombination efficiency

Horizontal transfer of mobile genetic elements, such as integrating and conjugative elements (ICEs), plays an important role in generating diversity and maintaining comprehensive pan-genomes in bacterial populations. The human gastric pathogen Helicobacter pylori, which is known for its extreme genetic diversity, possesses highly efficient transformation and recombination systems to achieve this diversity, but it is unclear to what extent these systems influence ICE physiology. In this study, we have examined the excision/integration and horizontal transfer characteristics of an ICE (termed ICEHptfs4) in these bacteria. We show that transfer of ICEHptfs4 DNA during mating between donor and recipient strains is independent of its conjugation genes, and that homologous recombination is much more efficient than site-specific integration into the recipient chromosome. Nevertheless, ICEHptfs4 excision by site-specific recombination occurs permanently in a subpopulation of cells and involves relocation of a circularization-dependent promoter. Selection experiments for excision indicate that the circular form of ICEHptfs4 is not replicative, but readily reintegrates by site-specific recombination. Thus, although ICEHptfs4 harbours all essential transfer genes, and typical ICE functions such as site-specific integration are active in H. pylori, canonical ICE transfer is subordinate to the more efficient general DNA uptake and homologous recombination machineries in these bacteria.

Mitochondrial Architecture Rearrangements Produce Asymmetrical Nonadaptive Mutational Pressures That Subvert the Phylogenetic Reconstruction in Isopoda.

The phylogeny of Isopoda, a speciose order of crustaceans, remains unresolved, with different data sets (morphological, nuclear, mitochondrial) often producing starkly incongruent phylogenetic hypotheses. We hypothesized that extreme diversity in their life histories might be causing compositional heterogeneity/heterotachy in their mitochondrial genomes, and compromising the phylogenetic reconstruction. We tested the effects of different data sets (mitochondrial, nuclear, nucleotides, amino acids, concatenated genes, individual genes, gene orders), phylogenetic algorithms (assuming data homogeneity, heterogeneity, and heterotachy), and partitioning; and found that almost all of them produced unique topologies. As we also found that mitogenomes of Asellota and two Cymothoida families (Cymothoidae and Corallanidae) possess inversed base (GC) skew patterns in comparison to other isopods, we concluded that inverted skews cause long-branch attraction phylogenetic artifacts between these taxa. These asymmetrical skews are most likely driven by multiple independent inversions of origin of replication (i.e., nonadaptive mutational pressures). Although the PhyloBayes CAT-GTR algorithm managed to attenuate some of these artifacts (and outperform partitioning), mitochondrial data have limited applicability for reconstructing the phylogeny of Isopoda. Regardless of this, our analyses allowed us to propose solutions to some unresolved phylogenetic debates, and support Asellota are the most likely candidate for the basal isopod branch. As our findings show that architectural rearrangements might produce major compositional biases even on relatively short evolutionary timescales, the implications are that proving the suitability of data via composition skew analyses should be a prerequisite for every study that aims to use mitochondrial data for phylogenetic reconstruction, even among closely related taxa.

Identifying agriculture land acquisitions for alleviating future food security concerns

Abstract The total available land for food, fuel, or forests is finite, while land demand is increasing and expected to increase further in the coming decades; resulting in deterioration of food security. Therefore, the corporate world adopted a solution of acquiring international agricultural land. Consequently, the global demand for land has progressively risen, but the question requiring decision support is - which lands to acquire for food production to ensure future food security? Food Science and Technology has vital pivotal roles to play in improving this situation, as food science is inherently multidisciplinary and motivated by the use of new technologies. In this paper, we endeavour to address this multidisciplinary food science question, by considering 16 Middle East North Africa (MENA) region countries having extreme economic diversity and enormous variation in adaptive capacity. Our study parameters consist of CO2 fertilization, water scarcity and meta-parameter of climate change vulnerability. Using logical inference and principal of separate modifiability, major food security concerns were identified for 2030.

Association between iscR-based phylogeny, serovars and potential virulence markers of Haemophilus parasuis.

Haemophilus parasuis is an economically important bacterial pathogen of swine. Extensive genetic and phenotypic heterogeneity among H. parasuis strains have been observed, which hinders the deciphering of the population structure and its association with clinical virulence. In this study, two highly divergent clades were defined according to iron–sulphur cluster regulator (iscR)-based phylogeny analysis of 148 isolates. Clear separation of serovars and potential virulence markers (PVMs) were observed between the two clades, which are indicative of independent evolution of the two lineages. Previously suggested virulence factors showed no correlation with clinical virulence, and were probably clade or serovar specific genes emerged during different stage of evolution. PVMs profiles varied widely among isolates in the same serovar. Higher strain diversity in respect of PVMs was found for isolates from multi-strain infected farms than those from single strain infected ones, which indicates that multi-strain infection in one farm may increase the frequency of gene transfer in H. parasuis. Systemic isolates were more frequently found in serovar 13 and serovar 12, while no correlation between clinical virulence and iscR-based phylogeny was observed. It shows that iscR is a reliable marker for studying population structure of H. parasuis, while other factors should be included to avoid the interference of gene exchange of iscR between isolates. The two lineages of H. parasuis may have undergone independent evolution, but show no difference in clinical virulence. Wide distribution of systemic isolates across the entire population poses new challenge for development of vaccine with better cross-protection. Our study provides new information for better deciphering the population structure of H. parasuis, which helps understanding the extreme diversity within this pathogenic bacterium.

Genomics and immunity of the Mediterranean mussel Mytilus galloprovincialis in a changing environment

The Mediterranean mussel (Mytilus galloprovincialis) is a marine invasive species cultured all over the world. Mussels are an appreciated resource in local aquaculture enterprises because of their robust production and resilience that translates into a reliable economic value. So far, no massive mortalities have been reported in natural or cultured populations of this species. In the last years, the knowledge about its immune system has greatly improved but there are still many questions to be answered. One of them is why mussels, with their high filtering activity, are able to be exposed to a high number of potential pathogens without getting infected and without developing an elevated inflammatory response.The sequencing of the mussel genome has revealed a very complex organization with high heterozygosity, abundance of repetitive sequences and extreme intraspecific sequence diversity among individuals, mainly in immune related genes. Among those genes, antimicrobial peptides are the most expressed gene families in mussels, highly polymorphic and with antimicrobial effect against molluscs pathogens, but also against pathogens of lower vertebrates and humans. The combination of a complex genome with the adaptation of mussel immune system to a changing environment could explain this high variability, not only in immune-related genes, but also in the functional response among individuals sampled in the same location and date.

Biological and Structural Diversity of Type IV Secretion Systems.

The bacterial type IV secretion systems (T4SSs) are a functionally diverse superfamily of secretion systems found in many species of bacteria. Collectively, the T4SSs translocate DNA and monomeric and multimeric protein substrates to bacterial and eukaryotic cell types. T4SSs are composed of two large subfamilies, the conjugation machines and the effector translocators that transmit their cargoes through establishment of direct donor-target cell contacts, and a third small subfamily capable of importing or exporting substrates from or to the milieu. This review summarizes recent mechanistic and structural findings that are shedding new light on how T4SSs have evolved such functional diversity. Translocation signals are now known to be located C terminally or embedded internally in structural folds; these signals in combination with substrate-associated adaptor proteins mediate the docking of specific substrate repertoires to cognate VirD4-like receptors. For the Legionella pneumophila Dot/Icm system, recent work has elucidated the structural basis for adaptor-dependent substrate loading onto the VirD4-like DotL receptor. Advances in definition of T4SS machine structures now allow for detailed comparisons of nanomachines closely related to the Agrobacterium tumefaciens VirB/VirD4 T4SS with those more distantly related, e.g., the Dot/Icm and Helicobacter pylori Cag T4SSs. Finally, it is increasingly evident that T4SSs have evolved a variety of mechanisms dependent on elaboration of conjugative pili, membrane tubes, or surface adhesins to establish productive contacts with target cells. T4SSs thus have evolved extreme functional diversity through a plethora of adaptations impacting substrate selection, machine architecture, and target cell binding.

Divergent Allele Advantage Provides a Quantitative Model for Maintaining Alleles with a Wide Range of Intrinsic Merits.

The Major Histocompatibility Complex (MHC) is the most genetically diverse region of the genome in most vertebrates. Some form of balancing selection is necessary to account for the extreme diversity, but the precise mechanism of balancing selection is unknown. Due to the way MHC molecules determine immune recognition, overdominance (also referred to as heterozygote advantage) has been suggested as the main driving force behind this unrivalled diversity. However, both theoretical results and simulation models have shown that overdominance in its classical form cannot maintain large numbers of alleles unless all alleles confer unrealistically similar levels of fitness. There is increasing evidence that heterozygotes containing genetically divergent alleles allow for broader antigen presentation to immune cells, providing a selective mechanism for MHC polymorphism. By framing competing models of overdominance within a general framework, we show that a model based on Divergent Allele Advantage (DAA) provides a superior mechanism for maintaining alleles with a wide range of intrinsic merits, as intrinsically less-fit MHC alleles that are more divergent can survive under DAA. Specifically, our results demonstrate that a quantitative mechanism built from the DAA hypothesis is able to maintain polymorphism in the MHC. Applying such a model to both livestock breeding and conservation could provide a better way of identifying superior heterozygotes, and quantifying the advantages of genetic diversity at the MHC.

Comparative reproductive function in cervids: implications for management of farm and zoo populations

The cervids represent a complex assemblage of taxa characterized by extreme diversity in morphology, physiology, ecology and geographical distribution. Farmed species (for example red deer and fallow deer) are usually the common larger-bodied, gregarious and monotocous species that express marked reproductive seasonality in their temperate environment. Their commercial importance has facilitated considerable research into reproductive physiology and the development of assisted reproductive technologies (ART). In contrast, the remaining species, including many of tropical origin, show wide diversity in reproductive patterns, have generally received little scientific scrutiny, and include a number of endangered taxa that are reliant on ex situ conservation efforts (such as captive breeding) to ensure their survival. Domestication and ex situ management programmes have been associated with widespread translocation of various cervid species around the world, often placing the animals in environments that are not compatible with their evolved reproductive patterns. For example, the summer calving/lactation pattern of red deer, attuned to northern continental climatic patterns, is frequently misaligned with seasonal changes in feed availability in the Australasian pastoral environment. Similarly, seasonal or aseasonal calving patterns of tropical species translocated to temperate regions are usually associated with increased perinatal mortality of calves born in cool seasons. Conversely, temperate species in tropical zones may exhibit aberrant reproductive patterns in the absence of biologically significant photoperiod fluctuations. ARTs, which presently include artificial insemination, embryo transfer and in vitro embryo production, have potential application to the genetic management and population growth of various cervid species. Although application to some farmed cervid species is widespread, these technologies are rarely directly transferable from farmed to endangered species. Even within species, ART protocols developed successfully for one genotype (i.e. subspecies) may be ineffective in another (for example superovulation of red deer and wapiti). Therefore, application to genetic management of endangered species necessitates prior research into their reproductive patterns. This is often difficult because of the rarity of the animals, a lack of suitable handling facilities for the particular species, and the timid nature of the deer. More recently, however, non-invasive reproductive profiling, based on remote collection and monitoring of excreted steroid metabolites, has facilitated such research.

Extreme mechanical diversity of human telomeric DNA revealed by fluorescence-force spectroscopy

G-quadruplexes (GQs) can adopt diverse structures and are functionally implicated in transcription, replication, translation, and maintenance of telomere. Their conformational diversity under physiological levels of mechanical stress, however, is poorly understood. We used single-molecule fluorescence-force spectroscopy that combines fluorescence resonance energy transfer with optical tweezers to measure human telomeric sequences under tension. Abrupt GQ unfolding with K+ in solution occurred at as many as four discrete levels of force. Added to an ultrastable state and a gradually unfolding state, there were six mechanically distinct structures. Extreme mechanical diversity was also observed with Na+, although GQs were mechanically weaker. Our ability to detect small conformational changes at low forces enabled the determination of refolding forces of about 2 pN. Refolding was rapid and stochastically redistributed molecules to mechanically distinct states. A single guanine-to-thymine substitution mutant required much higher ion concentrations to display GQ-like unfolding and refolded via intermediates, contrary to the wild type. Contradicting an earlier proposal, truncation to three hexanucleotide repeats resulted in a single-stranded DNA-like mechanical behavior under all conditions, indicating that at least four repeats are required to form mechanically stable structures.

Learning from Rivers

Learning from Rivers

ETHNIC MAP OF NORTHERN CAUCASUS IN THE LATE ANTIQUITY PERIOD (GENERAL REVIEW BASED ON WRITTEN SOURCES)

The ethnic map of the region of the Late Antiquity based on information of late classic authors (Plinius Maior, Claudius Ptolemaeus, Strabo, etc.) with retrospective attraction of the data of the Early Medieval written sources and modern etnonymics of the North Caucasus, characterized by extreme diversity, is presented in the article. The mentioned in the narrative sources tribes and their massive groups are compared with Pra-Abkhaz-Adyg and Pra-Daghestani-Nakh ethnic communities who would actively interact with the Sarmatian (Sarmato-Alanian) ethno-cultural world.

Women & Leadership: Leading under Extreme Diversity

Women & Leadership: Leading under Extreme Diversity

Fixing Mislabeling by Human Annotators Leveraging Conflict Resolution and Prior Knowledge

According to the "human in the loop" paradigm, machine learning algorithms can improve when leveraging on human intelligence, usually in the form of labels or annotation from domain experts. However, in the case of research areas such as ubiquitous computing or lifelong learning, where the annotator is not an expert and is continuously asked for feedback, humans can provide significant fractions of incorrect labels. We propose to address this issue in a series of experiments where students are asked to provide information about their behavior via a dedicated mobile application. Their trustworthiness is tested by employing an architecture where the machine uses all its available knowledge to check the correctness of its own and the user labeling to build a uniform confidence measure for both of them to be used when a contradiction arises. The overarching system runs through a series of modes with progressively higher confidence and features a conflict resolution component to settle the inconsistencies. The results are very promising and show the pervasiveness of annotation mistakes, the extreme diversity of the users' behaviors which provides evidence of the impracticality of a uniform fits-it-all solution, and the substantially improved performance of a skeptical supervised learning strategy.

Targeting Modified Lipids during Routine Lipidomics Analysis using HILIC and C30 Reverse Phase Liquid Chromatography coupled to Mass Spectrometry

Lipids are important biomolecules in all biological systems and serve numerous essential cellular functions. The global analysis of complex lipids is very challenging due to the extreme diversity in lipid structures. Variation in linkages and positions of fatty acyl chain(s) on the lipid backbone, functional group modification, occurrence of the molecular species as isomers or isobars are among some of the greatest challenges to resolve in lipidomics. In this work, we describe a routine analytical approach combining two liquid chromatography platforms: hydrophilic interaction (HILIC) and C30 reversed-phase chromatography (C30RP) coupled to high resolution mass spectrometry (HRMS) as complementary high throughput platforms to analyze complex lipid mixtures. Vascular plants (kale leaves and corn roots), rat brain and soil microbes were used as proxies to evaluate the efficiency of the enhanced approach to resolve traditional, as well as, modified lipids during routine lipidomics analysis. We report for the first time, the observation of a modified class of acylphosphatidylglycerol (acylPG) in corn roots by HILIC, and further resolution of the isomers using C30RP chromatography. We also used this approach to demonstrate the presence of high levels of N-monomethyl phosphatidylethanolamine (MMPE) in soil microbes, as well as to determine the regioisomers of lysophospholipids in kale leaves. Additionally, neutral lipids were demonstrated using C30RP chromatography in positive ion mode to resolve triacylglycerol isomers in rat brain. The work presented here demonstrates how the enhanced approach can more routinely permit novel biomarker discovery, or lipid metabolism in a wide range of biological samples.

Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus

BackgroundInfections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved.ResultsHere, we present a genome-wide analysis of two genetic crosses between ivermectin resistant and sensitive isolates of the parasitic nematode Haemonchus contortus, an economically important gastrointestinal parasite of small ruminants and a model for anthelmintic research. Whole genome sequencing of parental populations, and key stages throughout the crosses, identified extensive genomic diversity that differentiates populations, but after backcrossing and selection, a single genomic quantitative trait locus (QTL) localised on chromosome V was revealed to be associated with ivermectin resistance. This QTL was common between the two geographically and genetically divergent resistant populations and did not include any leading candidate genes, suggestive of a previously uncharacterised mechanism and/or driver of resistance. Despite limited resolution due to low recombination in this region, population genetic analyses and novel evolutionary models supported strong selection at this QTL, driven by at least partial dominance of the resistant allele, and that large resistance-associated haplotype blocks were enriched in response to selection.ConclusionsWe have described the genetic architecture and mode of ivermectin selection, revealing a major genomic locus associated with ivermectin resistance, the most conclusive evidence to date in any parasitic nematode. This study highlights a novel genome-wide approach to the analysis of a genetic cross in non-model organisms with extreme genetic diversity, and the importance of a high-quality reference genome in interpreting the signals of selection so identified.

Competitiveness through integration in the European Union Strategy for the Alpine Region: a ‘balanced development’ approach

ABSTRACTIn the last 10 years, the European Union has devoted specific attention and resources to the establishment of macro-regional strategies, with the objective of joining together transnational areas to favour the effective and organized management of common challenges. In most macro-regions, however, the identification of strategies to increase competitiveness is a rather difficult task, given the extreme internal diversity in economic activities. Focusing on the youngest macro-regional strategy – EUSALP – this paper highlights the specific combinations of territorial growth assets that allow to overcome the inefficient use of local abundant strategic resources, in line with a ‘balanced development’ approach. The results, obtained on the basis of a database gathered at NUTS3 level, are useful to provide policy suggestions to support the competitiveness of EUSALP through synergies and complementarities, according to a cooperation networks perspective.

QSARs to predict adsorption affinity of organic micropollutants for activated carbon and β-cyclodextrin polymer adsorbents

The removal of organic micropollutants (MPs) from water by means of adsorption is determined by the physicochemical properties of the adsorbent and the MPs. It is challenging to predict the removal of MPs by specific adsorbents due to the extreme diversity in physicochemical properties among MPs of interest. In this research, we established Quantitative Structure–Activity Relationships (QSARs) between the physicochemical properties of a diverse set of MPs and their distribution coefficients (KD) measured on coconut shell activated carbon (CCAC) and porous β-cyclodextrin polymer (P-CDP) adsorbents. We conducted batch experiments with a mixture of 200 MPs and used the data to calculate KD values for each MP on each adsorbent under conditions of infinite dilution (i.e., low adsorbate concentrations). We used computational software to calculate 3656 molecular descriptors for each MP. We then developed and applied a model-selection workflow to identify the most significant molecular descriptors for each adsorbent. The functional stability and predictive power of the resulting QSARs were confirmed with internal cross validation and external validation. The applicability domain of the QSARs was defined based on the most significant molecular descriptors selected into each QSAR. The QSARs are predictive tools for evaluating adsorption-based water treatment processes and provide new insights into CCAC and P-CDP adsorption mechanisms.

Microscopic imaging as a tool to target spatial and temporal extraction of bioactive compounds through ultrasound intensification

Unravelling a chain of events in ultrasound-assisted extraction (UAE) of bioactive compounds from plants has to start with a detailed description of destructuration at macroscopic and microscopic scale. The present work aims to study the impacts and interactions of UAE on the extreme complexity and diversity of plants structures. Three plant species were selected for their difference in specialized structures and their spatial distribution of secondary metabolites: bitter orange leaf (C. aurantium L.), blackcurrant leaf (R. nigrum L.), and artichoke leaf (C. scolymus L.). Different microscopic techniques (Cyto-histochemistry, stereomicroscopic analysis, Scanning Electron Microscopy (SEM)) have been used to understand the complexity of plant structures and to highlight ultrasound-induced impacts especially on metabolites storage structures, with a neat comparison with conventional “silent” extraction procedure. The main results indicate that spatial UAE impacts are strongly related to plant structures’ properties (morphology, thickness, etc.) and particularly to the nature and the chemical constitution of their storage specialized structures. From a temporal point of view, for all studied leaves, observed mechanisms followed a special order according to structures and their mechanical resistance level to ultrasound (US) treatment. Microscopic mapping of metabolites and structures should be considered as a decision tool during UAE to target intensification process.