Defense induction in marine macroalgae: Its prevalence, capabilities and limitations

Herbivory is an important biotic factor affecting algal biomass, abundance, and distribution. Especially in marine habitats, herbivores often consume 50 -100% of the macroalgal production. Algae are not only passive player in this interac-tion but have evolved a variety of strategies to cope with herbivory. One strat-egy is the production of chemical metabolites that function as defense against consumers. These metabolites can either be continuously present at bioactive concentrations (constitutive defense), or be produced ‘on demand’, i.e. when appropriate cues indicate presence of consumers (inducible defense). Ecologi-cal theory postulates that inducible defense should be favoured when the de-fense incurs costs to algal fitness, when the presence of herbivores is variable or when increased chemical variability enhances its effectiveness. In vascular plants, the occurrence and mechanisms of inducible defense are well documented. However, the prevalence of defense induction, the cues triggering in-duction, the interactions with other factors like stress, and the temporal dynam-ics of defense induction in macroalgae are generally not well understood. This thesis investigated the prevalence of defense induction and the nature of the inducing cues in the macroalgal species Fucus serratus, Fucus evanescens (Phaeophyceae), Delesseria sanguinea, Phyllophora pseudoceranoides, and Furcellaria lumbricalis (Rhodophyta) (Chapter I). These species are widely dis-tributed perennial seaweeds of the western Baltic and represent important habi-tats for many associated species. Also, the efficiency of two proposed induction cues, direct grazing and waterborne cues, were investigated. All tested red algae, D. sanguinea, P. pseudoceranoides and F. lumbricalis, in-duced defense in response to direct grazing. The brown algae F. evanescens and F. serratus also showed induced effects but these were not always signifi-cant in different types of feeding assays. This study supports recent findings that defense regulation in marine macroalgae is a rather common phenomenon, especially in the Baltic Sea.My further experiments focused on the bladderwrack Fucus vesiculosus. Its populations in the Baltic have declined strongly from the 1970s. This decline has been attributed to eutrophication leading to light limited conditions and associated changes in competitive interactions and grazing pressure. However, these statements are based on observational data without support of experi-mental evidence. This study demonstrated that F. vesiculosus in the Kiel Fjord is already light limited in 2 m water depth and its lethal depth limit lies between 4 - 6 m depth (Chapter II). Epibionts enhance the negative effect of reduced light conditions. The reduced depth distribution and consequently the massive biomass loss of the Fucus-population in the Baltic may be enhanced by the det-rimental effects of herbivores which stresses the ecological importance of algal resistance to consumption. Algal physiology and alga-herbivore interactions can be affected by abiotic factors. However, the interactions of environmental stress and defense, in particu-lar defense induction, have not been assessed so far. Climatic models predict a water temperature increase of ca. 4°C for the Baltic. This would lead to water temperatures comparable to those at Fucus’ southern distribution limit. They can, thus, be expected to represent a physiological stress for Fucus. To assess the interactive effects of reduced light and increased temperatures on the de-fensive performance of F. vesiculosus, I conducted a two-factorial experiment, which showed that reduced light conditions reduced growth rates significantly but had no effect on inducible defense at ambient temperatures (15°C), and that the predicted summer warming suppressed induced defensive responses completely. This study is one of the first that shows that abiotic stress can affect alga-herbivore interactions and therefore indirectly macroalgal population dy-namics. The coevolution of algal defense and herbivore tolerance of the defenses can result in high species specificities of the interactions. Temporal dynamics of induction and relaxation of defense may therefore be tuned the typical activity patterns of locally important herbivore species. This project identified the tempo-ral dynamics of antifeeding defense regulation in a marine macroalga, F. vesiculosus in response to its main consumer, the isopod Idotea baltica. Time lag of induction and relaxation of induced feeding resistance were assessed. F.vesiculosus induced defense 10 days after the onset of grazing by the isopod Idotea baltica. Defenses were relaxed within 2 - 4 days after cessation of grazing. Thus, defense seems to be deployed sparingly and only induced in longer periods of high grazing pressure to avoid substantial loss of tissue. This thesis gives new insights in the prevalence and the variability of induced resistance and its interactions with other biotic and abiotic factors, a study field which this thesis has started to examine. Also, I present a possible scenario what effects the predicted climate changes may have on the interactions of F. vesiculosus and its consumer I. baltica and how these changes may consequently affect the Fucus-populations in the Baltic

Verteidigungsinduktion bei marinen Makroalgen: Verbreitung, Vorteile und Beschränkungen

Herbivory is an important biotic factor affecting algal biomass, abundance, and distribution. Especially in marine habitats, herbivores often consume 50 -100% of the macroalgal production. Algae are not only passive player in this interac-tion but have evolved a variety of strategies to cope with herbivory. One strat-egy is the production of chemical metabolites that function as defense against consumers. These metabolites can either be continuously present at bioactive concentrations (constitutive defense), or be produced ‘on demand’, i.e. when appropriate cues indicate presence of consumers (inducible defense). Ecologi-cal theory postulates that inducible defense should be favoured when the de-fense incurs costs to algal fitness, when the presence of herbivores is variable or when increased chemical variability enhances its effectiveness. In vascular plants, the occurrence and mechanisms of inducible defense are well documented. However, the prevalence of defense induction, the cues triggering in-duction, the interactions with other factors like stress, and the temporal dynam-ics of defense induction in macroalgae are generally not well understood. This thesis investigated the prevalence of defense induction and the nature of the inducing cues in the macroalgal species Fucus serratus, Fucus evanescens (Phaeophyceae), Delesseria sanguinea, Phyllophora pseudoceranoides, and Furcellaria lumbricalis (Rhodophyta) (Chapter I). These species are widely dis-tributed perennial seaweeds of the western Baltic and represent important habi-tats for many associated species. Also, the efficiency of two proposed induction cues, direct grazing and waterborne cues, were investigated. All tested red algae, D. sanguinea, P. pseudoceranoides and F. lumbricalis, in-duced defense in response to direct grazing. The brown algae F. evanescens and F. serratus also showed induced effects but these were not always signifi-cant in different types of feeding assays. This study supports recent findings that defense regulation in marine macroalgae is a rather common phenomenon, especially in the Baltic Sea.My further experiments focused on the bladderwrack Fucus vesiculosus. Its populations in the Baltic have declined strongly from the 1970s. This decline has been attributed to eutrophication leading to light limited conditions and associated changes in competitive interactions and grazing pressure. However, these statements are based on observational data without support of experi-mental evidence. This study demonstrated that F. vesiculosus in the Kiel Fjord is already light limited in 2 m water depth and its lethal depth limit lies between 4 - 6 m depth (Chapter II). Epibionts enhance the negative effect of reduced light conditions. The reduced depth distribution and consequently the massive biomass loss of the Fucus-population in the Baltic may be enhanced by the det-rimental effects of herbivores which stresses the ecological importance of algal resistance to consumption. Algal physiology and alga-herbivore interactions can be affected by abiotic factors. However, the interactions of environmental stress and defense, in particu-lar defense induction, have not been assessed so far. Climatic models predict a water temperature increase of ca. 4°C for the Baltic. This would lead to water temperatures comparable to those at Fucus’ southern distribution limit. They can, thus, be expected to represent a physiological stress for Fucus. To assess the interactive effects of reduced light and increased temperatures on the de-fensive performance of F. vesiculosus, I conducted a two-factorial experiment, which showed that reduced light conditions reduced growth rates significantly but had no effect on inducible defense at ambient temperatures (15°C), and that the predicted summer warming suppressed induced defensive responses completely. This study is one of the first that shows that abiotic stress can affect alga-herbivore interactions and therefore indirectly macroalgal population dy-namics. The coevolution of algal defense and herbivore tolerance of the defenses can result in high species specificities of the interactions. Temporal dynamics of induction and relaxation of defense may therefore be tuned the typical activity patterns of locally important herbivore species. This project identified the tempo-ral dynamics of antifeeding defense regulation in a marine macroalga, F. vesiculosus in response to its main consumer, the isopod Idotea baltica. Time lag of induction and relaxation of induced feeding resistance were assessed. F.vesiculosus induced defense 10 days after the onset of grazing by the isopod Idotea baltica. Defenses were relaxed within 2 - 4 days after cessation of grazing. Thus, defense seems to be deployed sparingly and only induced in longer periods of high grazing pressure to avoid substantial loss of tissue. This thesis gives new insights in the prevalence and the variability of induced resistance and its interactions with other biotic and abiotic factors, a study field which this thesis has started to examine. Also, I present a possible scenario what effects the predicted climate changes may have on the interactions of F. vesiculosus and its consumer I. baltica and how these changes may consequently affect the Fucus-populations in the Baltic.Herbivorie beeinflusst wesentlich die Biomasse von Makroalgen, ihre Abundanzen und ihre Verbreitung. Insbesondere in marinen Systemen konsumieren Herbivore oft 50 – 100% der Algenproduktion. Jedoch spielen Algen nicht nur eine passive Rolle in ihren Interaktionen mit Herbivoren, sondern haben verschiedene Strategien entwickelt, um der Herbivorie zu begegnen. Eine Anpassung ist die Produktion von Sekundärmetaboliten mit Fraßhemmender Wirkung. Diese Metabolite können entweder kontinuierlich in aktiven Konzentrationen gebildet werden (konstitutive Verteidigung), oder die Produktion wird durch einen externen Reiz ausgelöst (induzierte Verteidigung). Induzierte Verteidigung ist von Vorteil, wenn die Verteidigung den Algen metabolische Kosten verursacht, der Fraßdruck von Konsumenten zeitlich variabel ist und eine erhöhte Variabilität der Verteidigung ihre Effektivität erhöht. Bei terrestrischen Pflanzen sind die Verbreitung und die Mechanismen der induzierten Verteidigung bereits ausgiebig dokumentiert worden. In Makroalgen sind jedoch die Verbreitung von induzierter Verteidigung und auch die induzierenden Reize kaum bekannt. Auch die Interaktionen mit anderen Faktoren wie Stress und die zeitliche Dynamik von Verteidigungsinduktion in Makroalgen sind unbekannt. Diese Arbeit untersuchte das Auftreten von induzierter Verteidigung und die Art der induzierenden Reize bei den Algenarten Fucus serratus, Fucus evanescens (Phaeophyceae), Delesseria sanguinea, Phyllophora pseudoceranoides und Furcellaria lumbricalis (Rhodophyta) (Kapitel I). Diese perennierenden Arten sind in der westlichen Ostsee weit verbreitet und bilden wichtige Habitate für viele assoziierte Organismen. Zudem wurde die Effektivität von den beiden Induktionsreizen direkter Fraß und Fraß an benachbarten Algenindividuen unter-sucht. Alle untersuchten Rotalgen, D. sanguinea, P. pseudoceranoides und F. lumbri-calis, reagierten auf direkten Fraß mit induzierter Verteidigung. Bei den Braunalgen F. serratus und F. evanescens konnten auch induzierte Effekte in Bezug auf Fraßverteidigung nachgewiesen werden, diese waren jedoch nicht konsistent über verschiedene Fraßversuche. Diese Ergebnisse unterstützen neuere Studien, die belegen, dass Verteidigungsinduktion in marinen Makroalgen ein verbreitetes Phänomen ist. Meine weiteren Studien beschäftigten sich mit dem Blasentang Fucus vesiculosus. Diese Algenart ist eine der wichtigsten strukturierenden Algenarten der Ostsee, jedoch ist seit den 1970ern ein stetiger Rückgang der Populationen in der Ostsee zu verzeichnen. Es wird angenommen, dass dieser Rückgang Kon-sequenz von Eutrophierungsprozessen ist und mit Lichtlimitation und Veränderungen von Konkurrenz- und Prädationsdrücken einhergeht. Diese Annahmen stützen sich jedoch bisher auf Feldbeobachtungen ohne durch experimentelle Daten unterstützt zu werden. Diese Studie zeigte, dass F. vesiculosus in der Kieler Förde schon ab 2 m Wassertiefe Licht-limitiert ist und die physiologische Tiefengrenze zwischen 4 – 6 m Tiefe liegt. Epibionten verstärkten den Effekt der Lichtlimitation. Diese reduzierte Tiefenverbreitung und der damit einhergehende Verlust immenser Biomasse könnten den Effekt von Herbivoren weiter verstärken und somit Verteidigungsmechanismen noch wichtiger machen. Sowohl die Algenphysiologie, als auch Algen-Herbivor Interaktionen können durch abiotische Faktoren beeinflusst werden. Jedoch wurden Interaktionen von abiotischem Stress und Fraßverteidigung, insbesondere Verteidigungsinduktion, bisher kaum untersucht. Klimamodelle sagen für die Ostsee eine zukünftige Erhöhung der Wassertemperatur von ca. 4°C voraus. Diese Wassertemperatur entspräche derer, die Fucus an seiner südlichen Verbreitungsgrenze noch toleriert und kann somit physiologischen Stress darstellen. Um die Auswirkungen von reduziertem Lichtangebot und erhöhten Temperaturen zu untersuchen, führte ich einen zwei-faktoriellen Versuch durch, der nachwies, dass ein redu-ziertes Lichtangebot bei momentan vorherrschenden Temperaturen (15°C) kei-nen Effekt auf die Verteidigungsinduktion von Fucus hat, obwohl die Wachs-tumsraten signifikant reduziert wurden. Eine Temperaturerhöhung auf 20°C verhinderte jedoch jegliche Verteidigungsinduktion. Dadurch ist diese Studie eine der ersten, die nachweisen konnte, dass abiotische Stressfaktoren Einflussauf Algen-Herbivor Interaktion nehmen und somit auch indirekt Populationen von Makroalgen beeinflussen können. Die Koevolution von Verteidigung bei Algen und die Anpassungen der Herbivo-ren an die Verteidigung können zu sehr hoher Artspezifität dieser Interaktionen führen. Die zeitliche Dynamik von Verteidigungsinduktion- und deren Reduktion kann deshalb sehr spezifisch an die Herbivorenart angepasst sein. Ein Versuch dieser Arbeit löste sehr akkurat die zeitliche Dynamik der Verteidigungsinduktion von F. vesiculosus in Antwort auf Fraß der Meerassel Idotea baltica auf. Der Zeitraum bis zur effektiven Verteidigungsinduktion und die Abnahme der induzierten Verteidigung nach Beendigung des Fraßdrucks wurden quantifiziert und zeigten, dass Fucus nach zehn Tagen Fraßdruck von Idotea Verteidigung induziert. Bereits 2 - 4 Tage nach Beendigung des Fraßes wurde die Verteidigung wieder reduziert. Diese Ergebnisse weisen deutlich darauf hin, dass Verteidigung sparsam und nur nach längeren Fraßperioden eingesetzt wird, um substanziellen Verlust von Biomasse zu vermeiden. Die vorliegende Arbeit bietet neue Erkenntnisse im Bereich der Prävalenz von Verteidigungsinduktion bei Makroalgen, der Variabilität von induzierter Verteidigung und den Interaktionen von Verteidigung mit biotischen und abiotischen Faktoren. Sie stellt zudem ein mögliches Szenario vor, wie sich die Klimaveränderungen auf die Interaktionen von F. vesiculosus und des Konsumenten I. baltica auswirken können und somit indirekt Einfluss auf die Fucus-Populationen der Ostsee nehmen können

Effects of limitation stress and disruptive stress on induced antigrazing defense in the bladder wrack Fucus vesiculosus

We assessed the effects of light limitation and temperature shift on palatability and induced antiherbivore defense in the brown alga Fucus vesiculosus L. Incubation for 2 wk at light intensities above the compensation point of photosynthesis and in the absence of grazers increased the palatability of F. vesiculosus and its subsequent consumption by the omnivorous isopod Idotea baltica Pallas. This effect correlated with an increased C:N ratio and mannitol content in the algal tissue, presumably due to increased photosynthetic carbon fixation. Mannitol, the primary product of photosynthesis in F. vesiculosus, proved to be a feeding cue for I. baltica, and depletion of the mannitol pool may therefore account for the reduced palatability during light limitation. At light intensities above the compensation point of photosynthesis, F. vesiculosus responded with decreasing palatability when it was exposed to I. baltica grazing. Irrespective of the preceding light regime, such defense induction was prevented during incubation under light limitation. Thus, under low light, defense induction is not only inhibited, but also less necessary due to the relative absence of feeding cues. Upward or downward shifts in water temperature by approximately 10°C also inhibited inducible defense in F. vesiculosus. However, such shifts did not affect algal growth and were therefore the consequence of an impairment of specific defense-related components rather than of resource limitation, unless compensatory growth was given priority over defense

Perioperative course and accuracy of screw positioning in conventional, open robotic-guided and percutaneous robotic-guided, pedicle screw placement

Robotic-guided and percutaneous pedicle screw placement are emerging technologies. We here report a retrospective cohort analysis comparing conventional open to open robotic-guided and percutaneous robotic-guided pedicle screw placement. 112 patient records and CT scans were analyzed concerning the intraoperative and perioperative course. 35 patients underwent percutaneous, 20 open robotic-guided and 57 open conventional pedicle screw placement. 94.5% of robot-assisted and 91.4% of conventionally placed screws were found to be accurate. Percutaneous robotic and open robotic-guided subgroups did not differ obviously. Average X-ray exposure per screw was 34 s in robotic-guided compared to 77 s in conventional cases. Subgroup analysis indicates that percutaneously operated patients required less opioids, had a shorter hospitalization and lower rate of adverse events in the perioperative period. The use of robotic guidance significantly increased accuracy of screw positioning while reducing the X-ray exposure. Patients seem to have a better perioperative course following percutaneous procedures

DAM pilot project: Exclusion of bottom trawl fishery in marine protected areas of the German EEZ (North Sea) - DAM MPA Geo 1, Cruise No. HE588, October 24 - November 4, 2021, Bremerhaven (Germany) - Bremerhaven (Germany)

During HE588, data were collected in five research areas in the south-eastern part of the German Bight as part of the DAM Pilotmission on the exclusion of mobile bottom-contact fishing in the North Sea (www.mgf-nordsee.de). The cruise started on October 24, 2021, and had a duration of twelve days at sea. The conducted tasks consisted of seafloor mapping with hydroacoustic devices, multicoring and grab sampling from the seafloor surface, lander deployments for the study of current characteristics, and video and diving surveys of benthic fauna. Despite the unstable weather conditions, all scientific tasks could be conducted successfully within the allocated time

Anti-Fouling Effects of Saponin-Containing Crude Extracts from Tropical Indo-Pacific Sea Cucumbers

Sea cucumbers are bottom dwelling invertebrates, which are mostly found on subtropical and tropical sea grass beds, sandy reef flats, or reef slopes. Although constantly exposed to fouling communities in these habitats, many species are surprisingly free of invertebrate epibionts and microfouling algae such as diatoms. In our study, we investigated the anti-fouling (AF) activities of different crude extracts of tropical Indo-Pacific sea cucumber species against the fouling diatom Cylindrotheca closterium. Nine sea cucumber species from three genera (i.e., Holothuria, Bohadschia, Actinopyga) were selected and extracted to assess their AF activities. To verify whether the sea cucumber characteristic triterpene glycosides were responsible for the observed potent AF activities, we tested purified fractions enriched in saponins isolated from Bohadschia argus, representing one of the most active anti-fouling extracts. Saponins were quantified by vanillin-sulfuric acid colorimetric assays and identified by LC-MS and LC-MS/MS analyses. We were able to demonstrate that AF activities in sea cucumber extracts were species-specific, and growth inhibition as well as attachment of the diatom to surfaces is dependent on the saponin concentration (i.e., Actinopyga contained the highest quantities), as well as on the molecular composition and structure of the present saponins (i.e., Bivittoside D derivative was the most bioactive compound). In conclusion, the here performed AF assay represents a promising and fast method for selecting the most promising bioactive organism as well as for identifying novel compounds with potent AF activities for the discovery of potentially novel pharmacologically active natural products

Proteomic Investigation Uncovers Potential Targets and Target Sites of Pneumococcal Serine-Threonine Kinase StkP and Phosphatase PhpP

Like eukaryotes, different bacterial species express one or more Ser/Thr kinases and phosphatases that operate in various signaling networks by catalyzing phosphorylation and dephosphorylation of proteins that can immediately regulate biochemical pathways by altering protein function. The human pathogen Streptococcus pneumoniae encodes a single Ser/Thr kinase-phosphatase couple known as StkP-PhpP, which has shown to be crucial in the regulation of cell wall synthesis and cell division. In this study, we applied proteomics to further understand the physiological role of pneumococcal PhpP and StkP with an emphasis on phosphorylation events on Ser and Thr residues. Therefore, the proteome of the non-encapsulated D39 strain (WT), a kinase (ΔstkP), and phosphatase mutant (ΔphpP) were compared in a mass spectrometry based label-free quantification experiment. Results show that a loss of function of PhpP causes an increased abundance of proteins in the phosphate uptake system Pst. Quantitative proteomic data demonstrated an effect of StkP and PhpP on the two-component systems ComDE, LiaRS, CiaRH, and VicRK. To obtain further information on the function, targets and target sites of PhpP and StkP we combined the advantages of phosphopeptide enrichment using titanium dioxide and spectral library based data evaluation for sensitive detection of changes in the phosphoproteome of the wild type and the mutant strains. According to the role of StkP in cell division we identified several proteins involved in cell wall synthesis and cell division that are apparently phosphorylated by StkP. Unlike StkP, the physiological function of the co-expressed PhpP is poorly understood. For the first time we were able to provide a list of previously unknown putative targets of PhpP. Under these new putative targets of PhpP are, among others, five proteins with direct involvement in cell division (DivIVA, GpsB) and peptidoglycan biosynthesis (MltG, MreC, MacP)

Host-specific assembly of sponge-associated prokaryotes at high taxonomic ranks

Sponges (Porifera) are abundant and diverse members of benthic filter feeding communities in most marine ecosystems, from the deep sea to tropical reefs. A characteristic feature is the associated dense and diverse prokaryotic community present within the sponge mesohyl. Previous molecular genetic studies revealed the importance of host identity for the community composition of the sponge-associated microbiota. However, little is known whether sponge host-specific prokaryotic community patterns observed at 97% 16S rRNA gene sequence similarity are consistent at high taxonomic ranks (from genus to phylum level). In the present study, we investigated the prokaryotic community structure and variation of 24 sponge specimens (seven taxa) and three seawater samples from Sweden. Results show that the resemblance of prokaryotic communities at different taxonomic ranks is consistent with patterns present at 97% operational taxonomic unit level

Decreased depth distribution of Fucus vesiculosus (Phaeophyceae) in the Western Baltic: effects of light deficiency and epibionts on growth and photosynthesis

For many coastal areas of the world, a decrease in abundance and depth penetration of perennial macroalgae and seagrasses has been documented and attributed to eutrophication. A surplus of nutrients impairs perennial seaweeds in at least two ways: increased phytoplankton densities reduce the depth penetration of light and in addition filamentous seaweeds and microalgae growing epiphytically shade their perennial hosts. A reduction of depth limit and total abundance has also been observed for the brown seaweed Fucus vesiculosus at many sites in the Baltic Sea. However, in most cases the mechanistic reason for the loss of Fucus has been deduced from observations rather than from experimental evidence. Here, we present results of a two-factorial (water depth/light supply and epibionts) experiment that was run in the Kiel Fjord, western Baltic, from August to October 2005. Performance of F. vesiculosus was recorded by growth and chlorophyll measurements, PI-curves and in situ measurements of the photosynthetic activity as the relative rate of electron transport (rETR). rETR and growth decreased with water depth. Chlorophyll a concentrations increased with reduced light intensities, but this apparently could not compensate for the light deficiency. Epibionts enhanced the negative effect of reduced light conditions on growth. According to these findings we estimated the physiological depth limit of F. vesiculosus in the Kiel Fjord to lie between 4 and 6 m water depth

Towards an ICF core set for ADHD : a worldwide expert survey on ability and disability

This is the second in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF and Children and Youth version, ICF-CY) core sets for attention deficit hyperactivity disorder (ADHD). The objective of this stage was to gather the opinions from international experts on which ability and disability concepts were considered relevant to functioning in ADHD. An email-based survey was carried out amongst international experts in ADHD. Relevant functional ability and disability concepts were extracted from their responses and linked to the ICF/-CY categories by two independent researchers using a standardised linking procedure. 174 experts from 11 different disciplines and 45 different countries completed the survey. Meaningful concepts identified in their responses were linked to 185 ICF/-CY categories. Of these, 83 categories were identified by at least 5 % of the experts and considered the most relevant to ADHD: 30 of these were related to Body functions (most identified: attention functions, 85 %), 30 to Activities and Participation (most identified: school education, 52 %), 20 to Environmental factors (most identified: support from immediate family, 61 %), and 3 to Body structures (most identified: structure of brain, 83 %). Experts also provided their views on particular abilities related to ADHD, naming characteristics such as highenergy levels, flexibility and resiliency. Gender differences in the expression of ADHD identified by experts pertained mainly to females showing more internalising (e.g. anxiety,low self-esteem) and less externalising behaviours (e.g. hyperactivity), leading to a risk of late- and under-diagnosis in females. Results indicate that the impact of ADHD extends beyond the core symptom domains, into all areas of life and across the lifespan. The current study in combination with three additional preparatory studies (comprehensive scoping review, focus groups, clinical study) will provide the scientific basis to define the ADHD ICF/-CY core sets for multi-purpose use in basic and applied research and every day clinical practice