Mesophotic corals in Hawai'i maintain autotrophy to survive low-light conditions.

In mesophotic coral ecosystems, reef-building corals and their photosynthetic symbionts can survive with less than 1% of surface irradiance. How depth-specialist corals rely upon autotrophically and heterotrophically derived energy sources across the mesophotic zone remains unclear. We analysed the stable carbon (δ13C) and nitrogen (δ15N) isotope values of a Leptoseris community from the 'Au'au Channel, Maui, Hawai'i (65-125 m) including four coral host species living symbiotically with three algal haplotypes. We characterized the isotope values of hosts and symbionts across species and depth to compare trophic strategies. Symbiont δ13C was consistently 0.5‰ higher than host δ13C at all depths. Mean colony host and symbiont δ15N differed by up to 3.7‰ at shallow depths and converged at deeper depths. These results suggest that both heterotrophy and autotrophy remained integral to colony survival across depth. The increasing similarity between host and symbiont δ15N at deeper depths suggests that nitrogen is more efficiently shared between mesophotic coral hosts and their algal symbionts to sustain autotrophy. Isotopic trends across depth did not generally vary by host species or algal haplotype, suggesting that photosynthesis remains essential to Leptoseris survival and growth despite low light availability in the mesophotic zone.

Annual Research Review: 'There, the dance is - at the still point of the turning world' - dynamic systems perspectives on coregulation and dysregulation during early development.

During development we transition from coregulation (where regulatory processes are shared between child and caregiver) to self-regulation. Most early coregulatory interactions aim to manage fluctuations in the infant's arousal and alertness; but over time, coregulatory processes become progressively elaborated to encompass other functions such as sociocommunicative development, attention and executive control. The fundamental aim of coregulation is to help maintain an optimal 'critical state' between hypo- and hyperactivity. Here, we present a dynamic framework for understanding child-caregiver coregulatory interactions in the context of psychopathology. Early coregulatory processes involve both passive entrainment, through which a child's state entrains to the caregiver's, and active contingent responsiveness, through which the caregiver changes their behaviour in response to behaviours from the child. Similar principles, of interactive but asymmetric contingency, drive joint attention and the maintenance of epistemic states as well as arousal/alertness, emotion regulation and sociocommunicative development. We describe three ways in which active child-caregiver regulation can develop atypically, in conditions such as Autism, ADHD, anxiety and depression. The most well-known of these is insufficient contingent responsiveness, leading to reduced synchrony, which has been shown across a range of modalities in different disorders, and which is the target of most current interventions. We also present evidence that excessive contingent responsiveness and excessive synchrony can develop in some circumstances. And we show that positive feedback interactions can develop, which are contingent but mutually amplificatory child-caregiver interactions that drive the child further from their critical state. We discuss implications of these findings for future intervention research, and directions for future work.

Organellar genomic characterization of Anunuuluaehu liula representing a new genus and species of Phyllophoraceae (Gigartinales, Rhodophyta) from the mesophotic zone of Hawai'i.

Over the last 2 decades, routine collections in the Hawaiian Archipelago have expanded to mesophotic reefs, leading to the discovery of a new red algal genus and species, here described as Anunuuluaehu liula gen. et sp. nov. This study provides a detailed genus and species description and characterizes chloroplast and mitochondrial organellar genomes. The new genus, Anunuuluaehu, shares many characteristics with the family Phyllophoraceae and shows close similarities to Archestennogramma and Stenogramma, including habit morphology, nemathecia forming proliferations at the outer cortex with terminal chains of tetrasporangia, and carposporophytes with multi-layered pericarps. The single species in this genus exhibits distinctive features within the Phyllophoraceae: the presence of single-layer construction of large medullary cells and the development of long, tubular gonimoblastic filaments. Multi-gene phylogenetic analyses confirmed it as a unique, monophyletic lineage within the family. Cis-splicing genes, interrupted by intron-encoded proteins within group II introns, are present in both the chloroplast and mitochondrial genomes of A. liula. Notably, a specific region of the coxI group II intron exhibits similarity to fungal introns. Anunuuluaehu liula is presumed to be endemic to the Hawaiian Archipelago and thus far is known to live solely at mesophotic depths from Holaniku to Kaho'olawe ranging from 54 to 201 m, which is the deepest collection record of any representative in the family. Overall, this study enhances our understanding of the genomic and taxonomic complexities of red algae in mesophotic habitats, emphasizing the significance of continued research in this area to uncover further insights into evolutionary processes and biogeographic patterns.

Vocalization and physiological hyperarousal in infant-caregiver dyads where the caregiver has elevated anxiety.

Co-regulation of physiological arousal within the caregiver-child dyad precedes later self-regulation within the individual. Despite the importance of unimpaired self-regulatory development for later adjustment outcomes, little is understood about how early co-regulatory processes can become dysregulated during early life. Aspects of caregiver behavior, such as patterns of anxious speech, may be one factor influencing infant arousal dysregulation. To address this, we made day-long, naturalistic biobehavioral recordings in home settings in caregiver-infant dyads using wearable autonomic devices and miniature microphones. We examined the association between arousal, vocalization intensity, and caregiver anxiety. We found that moments of high physiological arousal in infants were more likely to be accompanied by high caregiver arousal when caregivers had high self-reported trait anxiety. Anxious caregivers were also more likely to vocalize intensely at states of high arousal and produce intense vocalizations that occurred in clusters. High-intensity vocalizations were associated with more sustained increases in autonomic arousal for both anxious caregivers and their infants. Findings indicate that caregiver vocal behavior differs in anxious parents, cooccurs with dyadic arousal dysregulation, and could contribute to physiological arousal transmission. Implications for caregiver vocalization as an intervention target are discussed.

In infancy, it's the extremes of arousal that are 'sticky': Naturalistic data challenge purely homeostatic approaches to studying self-regulation.

Most theoretical models of arousal/regulatory function emphasise the maintenance of homeostasis; consistent with this, most previous research into arousal has concentrated on examining individuals' recovery following the administration of experimentally administered stressors. Here, we take a different approach: we recorded day-long spontaneous fluctuations in autonomic arousal (indexed via electrocardiogram, heart rate variability and actigraphy) in a cohort of 82 typically developing 12-month-old infants while they were at home and awake. Based on the aforementioned models, we hypothesised that extreme high or low arousal states might be more short-lived than intermediate arousal states. Our results suggested that, contrary to this, both low- and high-arousal states were more persistent than intermediate arousal states. The same pattern was present when the data were viewed over multiple epoch sizes from 1 s to 5 min; over 10-15-minute time-scales, high-arousal states were more persistent than low- and intermediate states. One possible explanation for these findings is that extreme arousal states have intrinsically greater hysteresis; another is that, through 'metastatic' processes, small initial increases and decreases in arousal can become progressively amplified over time. Rather than exclusively using experimental paradigms to study recovery, we argue that future research should also use naturalistic data to study the mechanisms through which states can be maintained or amplified over time.

Herbaria macroalgae as a proxy for historical upwelling trends in Central California.

Planning for future ocean conditions requires historical data to establish more informed ecological baselines. To date, this process has been largely limited to instrument records and observations that begin around 1950. Here, we show how marine macroalgae specimens from herbaria repositories may document long-term ecosystem processes and extend historical information records into the nineteenth century. We tested the effect of drying and pressing six macroalgae species on amino acid, heavy metal and bulk stable isotope values over 1 year using modern and archived paper. We found historical paper composition did not consistently affect values. Certain species, however, had higher variability in particular metrics while others were more consistent. Multiple herbaria provided Gelidium (Rhodophyta) samples collected in southern Monterey Bay from 1878 to 2018. We examined environmental relationships and found δ15N correlated with the Bakun upwelling index, the productivity regime of this ecosystem, from 1946 to 2018. Then, we hindcasted the Bakun index using its derived relationship with Gelidium δ15N from 1878 to 1945. This hindcast provided new information, observing an upwelling decrease mid-century leading up to the well-known sardine fishery crash. Our case study suggests marine macroalgae from herbaria are an underused resource of the marine environment that precedes modern scientific data streams.

Influences of environmental stressors on autonomic function in 12-month-old infants: understanding early common pathways to atypical emotion regulation and cognitive performance.

BACKGROUND: Previous research has suggested that children exposed to more early-life stress show worse mental health outcomes and impaired cognitive performance in later life, but the mechanisms subserving these relationships remain poorly understood. METHOD: Using miniaturised microphones and physiological arousal monitors (electrocardiography, heart rate variability and actigraphy), we examined for the first time infants' autonomic reactions to environmental stressors (noise) in the home environment, in a sample of 82 12-month-old infants from mixed demographic backgrounds. The same infants also attended a laboratory testing battery where attention- and emotion-eliciting stimuli were presented. We examined how children's environmental noise exposure levels at home related to their autonomic reactivity and to their behavioural performance in the laboratory. RESULTS: Individual differences in total noise exposure were independent of other socioeconomic and parenting variables. Children exposed to higher and more rapidly fluctuating environmental noise showed more unstable autonomic arousal patterns overall in home settings. In the laboratory testing battery, this group showed more labile and short-lived autonomic changes in response to novel attention-eliciting stimuli, along with reduced visual sustained attention. They also showed increased arousal lability in response to an emotional stressor. CONCLUSIONS: Our results offer new insights into the mechanisms by which environmental noise exposure may confer increased risk of adverse mental health and impaired cognitive performance during later life.

New Ulvaceae (Ulvophyceae, Chlorophyta) from mesophotic ecosystems across the Hawaiian Archipelago.

Ulvalean algae (Chlorophyta) are most commonly described from intertidal and shallow subtidal marine environments worldwide, but are less well known from mesophotic environments. Their morphological simplicity and phenotypic plasticity make accurate species determinations difficult, even at the generic level. Here, we describe the mesophotic Ulvales species composition from 13 locations across 2,300 km of the Hawaiian Archipelago. Twenty-eight representative Ulvales specimens from 64 to 125 m depths were collected using technical diving, submersibles, and remotely operated vehicles. Morphological and molecular characters suggest that mesophotic Ulvales in Hawaiian waters form unique communities comprising four species within the genera Ulva and Umbraulva, each with discrete geographic and/or depth-related distributional patterns. Three genetically distinct taxa are supported by both plastid (rbcL and tufA) and nuclear (ITS1) markers, and are presented here as new species: Umbraulva kaloakulau, Ulva ohiohilulu, and Ulva iliohaha. We also propose a new Umbraulva species (Umbraulva kuaweuweu), which is closely related to subtidal records from New Zealand and Australia, but not formally described. To our knowledge, these are the first marine species descriptions from Hawai'i resulting from the collaboration of traditional Hawaiian nomenclature specialists, cultural practitioners and scientists. The difficulty of finding reliable diagnostic morphological characters for these species reflects a common problem worldwide of achieving accurate identification of ulvalean taxa using solely morphological criteria. Mesophotic Ulvales appear to be distinct from shallow-water populations in Hawai'i, but their degree of similarity to mesophotic floras in other locations in the Pacific remains unknown.

Divergent responses of native and invasive macroalgae to submarine groundwater discharge.

Marine macroalgae are important indicators of healthy nearshore groundwater dependent ecosystems (GDEs), which are emergent global conservation priorities. Submarine groundwater discharge (SGD) supports abundant native algal communities in GDEs via elevated but naturally derived nutrients. GDEs are threatened by anthropogenic nutrient inputs that pollute SGD above ambient levels, favoring invasive algae. Accordingly, this case study draws on the GDE conditions of Kona, Hawai'i where we evaluated daily photosynthetic production and growth for two macroalgae; a culturally valued native (Ulva lactuca) and an invasive (Hypnea musciformis). Manipulative experiments-devised to address future land-use, climate change, and water-use scenarios for Kona-tested algal responses under a natural range of SGD nutrient and salinity levels. Our analyses demonstrate that photosynthesis and growth in U. lactuca are optimal in low-salinity, high-nutrient waters, whereas productivity for H. musciformis appears limited to higher salinities despite elevated nutrient subsidies. These findings suggest that reductions in SGD via climate change decreases in rainfall or increased water-use from the aquifer may relax physiological constraints on H. musciformis. Collectively, this study reveals divergent physiologies of a native and an invasive macroalga to SGD and highlights the importance of maintaining SGD quantity and quality to protect nearshore GDEs.

Laser-Induced Fluorescence for Monitoring Environmental Contamination and Stress in the Moss Thuidium plicatile.

The ability to detect, measure, and locate the source of contaminants, especially heavy metals and radionuclides, is of ongoing interest. A common tool for contaminant identification and bioremediation is vegetation that can accumulate and indicate recent and historic pollution. However, large-scale sampling can be costly and labor-intensive. Hence, non-invasive in-situ techniques such as laser-induced fluorescence (LIF) are becoming useful and effective ways to observe the health of plants through the excitation of organic molecules, e.g., chlorophyll. The technique presented utilizes images collected of LIF in moss to identify different metals and environmental stressors. Analysis through image processing of LIF response was key to identifying Cu, Zn, Pb, and a mixture of the metals at nmol/cm2 levels. Specifically, the RGB values from each image were used to create density histograms of each color channel's relative pixel abundance at each decimal code value. These histograms were then used to compare color shifts linked to the successful identification of contaminated moss samples. Photoperiod and extraneous environmental stressors had minimal impact on the histogram color shift compared to metals and presented with a response that differentiated them from metal contamination.

Introduced mangroves escape damage from marine and terrestrial enemies.

The enemy release hypothesis (ERH) posits that introduced species often leave their enemies behind when introduced to a new range. This release from enemies may allow introduced species to achieve higher growth and reproduction and may explain why some invaders flourish in new locations. Red mangroves (Rhizophora mangle) were introduced to Hawai'i from Florida over a century ago. Because Hawai'i has no native mangroves, the arrival of R. mangle fundamentally changed the structure and function of estuarine shorelines. While numerous enemies affect red mangroves in their native range (tropical America), in Hawai'i, mangroves apparently experience little herbivory, which may explain why introduced mangroves are so productive, fecund, and continue to spread. In this study, we compared the effects of enemies in native and introduced populations of brackish red mangroves (R. mangle) in 8-10 sites in the native range (Florida, Belize, and Panama) and introduced range of mangroves (Hawai'i). At each site, we measured the (1) occurrence of enemies using timed visual surveys, (2) occurrence of damage to different mangrove structures (leaves, apical buds, dead twigs, roots, propagules, and seedlings), and (3) rate of propagule herbivory using tethering experiments. Consistent with the ERH, we found an order of magnitude less damage and fewer enemies in introduced than native mangrove sites. While introduced mangroves harbored few enemies and minimal damage, native mangroves were affected by numerous enemies, including leaf-eating crabs, specialist bud moths, wood-boring insects and isopods, and propagule predators. These patterns were consistent across all plant structures (roots to leaves), among marine and terrestrial enemies, and across functional groups (browsers, borers, pathogens, etc.), which demonstrates enemy escape occurs consistently among different functional groups and via trophic (e.g., herbivores) and non-trophic (e.g., root borers) interactions. Our study is among the first biogeographical enemy release studies to take a comprehensive approach to quantifying the occurrence of damage from a broad suite of marine and terrestrial taxa across an array of wetland plant structures. Understanding how natural enemies alter this key foundation species will become increasingly relevant globally as mangroves continue to invade new regions through intentional plantings or range expansion driven by climate change.

Protocol to control the invasive alga Avrainvillea lacerata in a shallow Hawaiian reef flat.

Premise: A novel control technique was developed to mitigate an invasive siphonous green alga, Avrainvillea lacerata (Dichotomosiphonaceae), within a shallow degraded reef flat in O'ahu, Hawai'i. Methods and Results: Replicated treatments of 3% and 10% hydrogen peroxide (H2O2) were administered into individual basal attachments of the bed-forming invasive seaweed on the Paiko reef, O'ahu. Relative electron transport rate maxima (rETRm) were measured using a Walz Diving Pulse Amplitude Modulated Fluorometer in two replicate 100-m2 plots in 2020. Over the period of this short-term study, rETRm decreased following injections of either concentration of H2O2 in contrast with negative and positive controls. Conclusions: Compared with existing techniques that have used oxidizing agents in the marine environment in localized areas, the protocol described here has the potential to successfully decrease macroalgal carbon gain, potentially leading to loss of biomass at larger scales.

The effect of perinatal interventions on parent anxiety, infant socio-emotional development and parent-infant relationship outcomes: A systematic review.

Background: Infants of parents with perinatal anxiety are at elevated likelihood of experiencing disruption in the parent-infant relationship, as well as difficulties with socio-emotional functioning in later development. Interventions delivered in the perinatal period have the potential to protect the early dyadic relationship and support infants' ongoing development and socio-emotional outcomes. This review primarily aimed to examine the efficacy of perinatal interventions on parent anxiety, infant socio-emotional development/temperament, and parent-infant relationship outcomes. Secondarily, the review sought to understand how interventions focused principally on one member of the dyad affected the outcomes of the other, and which intervention components were common to successful interventions. Method: Five electronic databases as well as manual search procedures were used to identify randomised controlled trials according to a PICO eligibility criteria framework. Risk of bias assessments were undertaken, and a narrative synthesis was conducted. The review was pre-registered on PROSPERO (CRD42021254799). Results: Twelve studies were analysed in total, including five interventions focused on the adult, and seven interventions focused on the infant, or the infant's relationship with their parent. Interventions incorporating cognitive behavioural strategies for affective disorders showed reductions in parent anxiety (N = 3), and interventions focusing on altering distorted maternal internal representations showed positive change in parent-child dyadic interactions, and infant outcomes (N = 2). Evidence that interventions focused on one partner of the dyad led to improved outcomes for the other partner was limited. However, evidence was of mixed methodological quality. Conclusions: It is important to integrate both parents and infants into treatment programmes for perinatal anxiety. Implications for clinical practice and future intervention trials are discussed.

Vocal communication is tied to interpersonal arousal coupling in caregiver-infant dyads.

It has been argued that a necessary condition for the emergence of speech in humans is the ability to vocalise irrespective of underlying affective states, but when and how this happens during development remains unclear. To examine this, we used wearable microphones and autonomic sensors to collect multimodal naturalistic datasets from 12-month-olds and their caregivers. We observed that, across the day, clusters of vocalisations occur during elevated infant and caregiver arousal. This relationship is stronger in infants than caregivers: caregivers vocalisations show greater decoupling with their own states of arousal, and their vocal production is more influenced by the infant's arousal than their own. Different types of vocalisation elicit different patterns of change across the dyad. Cries occur following reduced infant arousal stability and lead to increased child-caregiver arousal coupling, and decreased infant arousal. Speech-like vocalisations also occur at elevated arousal, but lead to longer-lasting increases in arousal, and elicit more parental verbal responses. Our results suggest that: 12-month-old infants' vocalisations are strongly contingent on their arousal state (for both cries and speech-like vocalisations), whereas adults' vocalisations are more flexibly tied to their own arousal; that cries and speech-like vocalisations alter the intra-dyadic dynamics of arousal in different ways, which may be an important factor driving speech development; and that this selection mechanism which drives vocal development is anchored in our stress physiology.

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset.

BACKGROUND: Diabetes like many diseases and biological processes is not mono-causal. On the one hand multi-factorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics. RESULTS: We present a comprehensive work-flow tailored for analyzing complex data including data from multi-factorial studies. The developed approach aims at revealing effects caused by a distinct combination of experimental factors, in our case genotype and diet. Applying the developed work-flow to the analysis of an established polygenic mouse model for diet-induced type 2 diabetes, we found peptides with significant fold changes exclusively for the combination of a particular strain and diet. Exploitation of redundancy enables the visualization of peptide correlation and provides a natural way of feature selection for classification and prediction. Classification based on the features selected using our approach performs similar to classifications based on more complex feature selection methods. CONCLUSIONS: The combination of ANOVA and redundancy exploitation allows for identification of biomarker candidates in multi-dimensional MALDI-TOF MS profiling studies with complex experimental design. With respect to feature selection our method provides a fast and intuitive alternative to global optimization strategies with comparable performance. The method is implemented in R and the scripts are available by contacting the corresponding author.

Deciphering the complexity of sainfoin (Onobrychis viciifolia) proanthocyanidins by MALDI-TOF mass spectrometry with a judicious choice of isotope patterns and matrixes.

Use of superdihydroxybenzoic acid as the matrix enabled the analysis of highly complex mixtures of proanthocyanidins from sainfoin (Onobrychis viciifolia) by MALDI-TOF mass spectrometry. Proanthocyanidins contained predominantly B-type homopolymers and heteropolymers up to 12-mers (3400 Da). Use of another matrix, 2,6-dihydroxyacetophenone, revealed the presence of A-type glycosylated dimers. In addition, we report here how a comparison of the isotopic adduct patterns, which resulted from Li and Na salts as MALDI matrix additives, could be used to confirm the presence of A-type linkages in complex proanthocyanidin mixtures. Preliminary evidence suggested the presence of A-type dimers in glycosylated prodelphinidins and in tetrameric procyanidins and prodelphinidins.

Physiological stress, sustained attention, emotion regulation, and cognitive engagement in 12-month-old infants from urban environments.

Over the last 2 centuries there has been a rapid increase in the proportion of children who grow up in cities. However, relatively little work has explored in detail the physiological and cognitive pathways through which city life may affect early development. To assess this, we observed a cohort of infants growing up in diverse settings across South East England across a 2-day assessment battery. On Visit 1, day-long home recordings were made to monitor infants' physiological stress in real-world settings. On Visit 2, lab batteries were administered to measure infants' cognitive, emotional, and neural reactivity. Infants from more high-density urban environments showed increased physiological stress (decreased parasympathetic nervous system activity) at home. This relationship was independent of socioeconomic status and lifelong stressors. Behaviorally, infants raised in high-density settings showed lower sustained attention in the lab, along with increased behavioral and physiological reactivity during an emotion elicitation task. However, they also showed increased recognition memory for briefly presented stimuli and increased neural engagement with novel stimuli. This pattern is consistent with other research into how elevated physiological stress influences cognition, and with theoretical approaches from adult research that predict that city life is associated with a profile of cognitive strengths as well as weaknesses. Implications for education and developmental psychopathology are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Identifying wastewater management tradeoffs: Costs, nearshore water quality, and implications for marine coastal ecosystems in Kona, Hawai'i.

Untreated and minimally treated wastewater discharged into the environment have the potential to adversely affect groundwater dependent ecosystems and nearshore marine health. Addressing this issue requires a systems approach that links land use and wastewater management decisions to potential impacts on the nearshore marine environment via changes in water quality and quantity. To that end, a framework was developed to assess decisions that have cascading effects across multiple elements of the ridge-to-reef system. In an application to Kona (Hawai'i, USA), eight land use and wastewater management scenarios were evaluated in terms of wastewater system upgrade costs and wastewater related nutrient loads in groundwater, which eventually discharge to nearshore waters, resulting in potential impacts to marine habitat quality. Without any upgrades of cesspools or the existing wastewater treatment plant (WWTP), discharges of nutrients are expected to increase substantially with permitted development, with potential detrimental impacts to the marine environment. Results suggest that converting all of the existing cesspools to aerobic treatment units (ATU) and upgrading the existing WWTP to R-1 quality provide the highest protection to nearshore marine habitat at a cost of $569 million in present value terms. Other wastewater management options were less effective but also less costly. For example, targeted cesspool conversion (a combination of septic and ATU installation) in conjunction with the WWTP upgrade still provided a substantial reduction in nutrients and potential impacts to marine habitat quality relative to the present situation at a price point roughly $100 million less than the entirely ATU option. Of note, results were more sensitive to the inclusion of the WWTP upgrade option than they were to assumptions regarding the efficiency of the cesspool conversion technologies. The model outputs also suggest that the spatial distribution of potential impacts should be carefully considered when comparing different wastewater management scenarios. When evaluated separately, the WWTP option reduced total nutrients by more than the targeted cesspool conversion option at a fraction of the cost. However, potential improvements in marine habitat quality only occurred in the immediate vicinity of the WWTP, whereas the benefits under targeted cesspool conversion were more evenly distributed along the coast.

A well-characterised peak identification list of MALDI MS profile peaks for human blood serum.

MALDI MS profiling, using easily available body fluids such as blood serum, has attracted considerable interest for its potential in clinical applications. Despite the numerous reports on MALDI MS profiling of human serum, there is only scarce information on the identity of the species making up these profiles, particularly in the mass range of larger peptides. Here, we provide a list of more than 90 entries of MALDI MS profile peak identities up to 10 kDa obtained from human blood serum. Various modifications such as phosphorylation were detected among the peptide identifications. The overlap with the few other MALDI MS peak lists published so far was found to be limited and hence our list significantly extends the number of identified peaks commonly found in MALDI MS profiling of human blood serum.

Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer.

BACKGROUND: The serum peptidome may be a valuable source of diagnostic cancer biomarkers. Previous mass spectrometry (MS) studies have suggested that groups of related peptides discriminatory for different cancer types are generated ex vivo from abundant serum proteins by tumor-specific exopeptidases. We tested 2 complementary serum profiling strategies to see if similar peptides could be found that discriminate ovarian cancer from benign cases and healthy controls. METHODS: We subjected identically collected and processed serum samples from healthy volunteers and patients to automated polypeptide extraction on octadecylsilane-coated magnetic beads and separately on ZipTips before MALDI-TOF MS profiling at 2 centers. The 2 platforms were compared and case control profiling data analyzed to find altered MS peak intensities. We tested models built from training datasets for both methods for their ability to classify a blinded test set. RESULTS: Both profiling platforms had CVs of approximately 15% and could be applied for high-throughput analysis of clinical samples. The 2 methods generated overlapping peptide profiles, with some differences in peak intensity in different mass regions. In cross-validation, models from training data gave diagnostic accuracies up to 87% for discriminating malignant ovarian cancer from healthy controls and up to 81% for discriminating malignant from benign samples. Diagnostic accuracies up to 71% (malignant vs healthy) and up to 65% (malignant vs benign) were obtained when the models were validated on the blinded test set. CONCLUSIONS: For ovarian cancer, altered MALDI-TOF MS peptide profiles alone cannot be used for accurate diagnoses.