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Abstract Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.

Abstract We introduce a novel, gaseous target optical shaping laser set-up, capable to generate short scale length, near-critical target profiles via generated colliding blast waves. These profiles are capable to maintain their compressed density for several nanoseconds, being therefore ideal for laser-plasma particle acceleration experiments in the near critical density plasma regime. Our proposed method overcomes the laser-target synchronization limitations and delivers energetic protons, during the temporal evolution of the optically shaped profile, in a time window of approximately 2.5 ns. The optical shaping of the gas-jet profiles is optimised by MagnetoHydroDynamic simulations. 3D Particle-In-Cell models, adopting the spatiotemporal profile, simulate the 45 TW femtosecond laser plasma interaction to demonstrate the feasibility of the proposed proton acceleration set-up. The optical shaping of gas-jets is performed by multiple, nanosecond laser pulse generated blastwaves. This process results in steep gradient, short scale length plasma profiles, in the near critical density regime allowing operation at high repetition rates. Notably, the Magnetic Vortex Acceleration mechanism exhibits high efficiency in coupling the laser energy into the plasma in the optically shaped targets, resulting to collimated proton beams of energies up to 14 MeV.

Abstract Laser plasma-based accelerators provide an excellent source of collimated, bright, and adequately coherent betatron-type x-ray pulses with potential applications in science and industry. So far the laser plasma-based betatron radiation has been described within the concept of classical Liénard–Wiechert potentials incorporated in particle-in-cell simulations, a computing power-demanding approach, especially for the case of multi-petawatt lasers. In this work, we describe the laser plasma-based generation of betatron radiation at the most fundamental level of quantum mechanics. In our approach, photon emission from the relativistic electrons in the plasma bubble is described within a nonlinear quantum electrodynamics (QED) framework. The reported QED-based betatron radiation results are in excellent agreement with similar results using Liénard–Wiechert potentials, as well as in very good agreement with betatron radiation measurements, obtained with multi-10-TW lasers interacting with He and multielectron N $$_2$$ 2 gas targets. Furthermore, our QED approach results in a dramatic reduction of the computational runtime demands, making it a favorable tool for designing betatron radiation experiments, especially in multi-petawatt laser facilities.

Abstract Beyond SARS‐CoV2 vaccines, mRNA drugs are being explored to overcome today's greatest healthcare burdens, including cancer and cardiovascular disease. Synthetic mRNA triggers immune responses in transfected cells, which can be reduced by chemically modified nucleotides. However, the side effects of mRNA‐triggered immune activation on cell function and how different nucleotides, such as the N1‐methylpseudouridine (m1Ψ) used in SARS‐CoV2 vaccines, can modulate cellular responses is not fully understood. Here, cellular responses toward a library of uridine‐modified mRNAs are investigated in primary human cells. Targeted proteomics analyses reveal that unmodified mRNA induces a pro‐inflammatory paracrine pattern marked by the secretion of chemokines, which recruit T and B lymphocytes toward transfected cells. Importantly, the magnitude of mRNA‐induced changes in cell function varies quantitatively between unmodified, Ψ‐, m1Ψ‐, and 5moU‐modified mRNA and can be gradually tailored, with implications for deliberately exploiting this effect in mRNA drug design. Indeed, both the immunosuppressive effect of stromal cells on T‐cell proliferation, and the anti‐inflammatory effect of IL‐10 mRNA are enhanced by appropriate uridine modification. The results provide new insights into the effects of mRNA drugs on cell function and cell‐cell communication and open new possibilities to tailor mRNA‐triggered immune activation to the desired pro‐ or anti‐inflammatory application.

Abstract The purpose of this retrospective study was to investigate response of sinonasal mucosal melanoma (SMM) patients to treatment with immune checkpoint inhibitors (ICI), using hybrid PET imaging. Fifteen SMM patients underwent hybrid PET imaging before and three months after initiation of ICI. The disease-specific survival (DSS) was calculated. Quantitative PET parameters of the primary tumor and their association with DSS and therapy response were investigated. Nine of the fifteen (60%) patients responded to ICI therapy. Patients with therapy response depicted on hybrid PET imaging had better DSS than those without (p = 0.0058). Quantitative PET parameters of the initial PET harbored no association with DSS or therapy response. However, these findings lack of sufficient statistical power and must be interpreted with caution. The first restaging PET-imaging after ICI initiation can help stratify patients with regard to DSS.

Abstract Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.

Abstract The temporal rearrangement of the spectral components of an ultrafast and intense laser pulse, i.e., the chirp of the pulse, offers significant possibilities for controlling its interaction with matter and plasma. In the propagation of ultra-strong laser pulses within the self-induced plasma, laser pulse chirp can play a major role in the dynamics of wakefield and plasma bubble formation, as well as in the electron injection and related electron acceleration. Here, we experimentally demonstrate the control of the generation efficiency of a relativistic electron beam, with respect to maximum electron energy and current, by accurately varying the chirp value of a multi-10-TW laser pulse. We explicitly show that positively chirped laser pulses, i.e., pulses with instantaneous frequency increasing with time, accelerate electrons in the order of 100 MeV much more efficiently in comparison to unchirped or negatively chirped pulses. Corresponding Particle-In-Cell simulations strongly support the experimental results, depicting a smoother plasma bubble density distribution and electron injection conditions that favor the maximum acceleration of the electron beam, when positively chirped laser pulses are used. Our results, aside from extending the validity of similar studies reported for PW laser pulses, provide the ground for understanding the subtle dynamics of an efficient plasma electron accelerator driven by chirped laser pulses.

Measurement(s) mRNA Sequencing Technology Type(s) Next Generation Sequencing Factor Type(s) Tissue Source • Tissue Type Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment cell culture

Abstract This study aimed to evaluate the safety and efficacy of innovative retinoic acid (RA) eluting stents with bioabsorbable polymer. Sixty stents divided in ten groups were implanted in the iliac arteries of 30 rabbits. Two polymers (“A”, poly (lactic-co-glycolic acid) and “B”, polylactic acid), and three doses (“Low”, “Medium” and “High”) of RA (groups: AL, AM, AH, BL, BM, BH) were used on cobalt chromium stents (Rontis Corporation), one group of bare stent (C), one group (D) of Everolimus eluting stent (Xience-Pro, Abbot Vascular), and two groups of Rontis Everolimus eluting stents coated with polymer A (EA) and B (EB). Treated arteries were explanted after 4 weeks, processed by methyl methacrylate resin and evaluated by histopathology. None of the implanted stents was related with thrombus formation or extensive inflammation. Image analysis showed limited differences between groups regarding area stenosis (BH, D and EB groups had the lower values). Group BH had lower intimal mean thickness than AH (105.1 vs 75.3 μm, p = 0.024). Stents eluting RA, a non-cytotoxic drug, were not related with thrombus formation and had an acceptable degree of stenosis 4 weeks post implantation. RA dose and type of polymer may play role in the biocompatibility of the stents.

Engineering micro-emulsion plays a key role in the creation of bottom-up synthetic cells. Here, authors demonstrate a droplet laboratory platform to control membrane protein gating in functional artificial cell using microfluidics and acoustic levitation.

In addition to food supply, there is a growing recognition of the wider ecosystem benefits of Integrated Multitrophic Aquaculture (IMTA) systems in coastal waters, including regulating services such as carbon sequestration and nutrient remediation. The water trophic status and the co-cultured species combinations affect IMTA productivity. In this study, we examined the ability of different combinations of IMTA organisms to remediate nutrients and the economic/environmental gain for reducing the environmental footprint in potential IMTA systems of the eastern Mediterranean. The results showed that the co-cultivation of organisms can reduce the negative effects on the marine environment of a fish farm both on the water column and the sediment. Meso- and eutrophic water states do not show a high variation in terms of foot print mitigation, with all three of the co-cultivated organisms to perform well. In oligotrophic waters, the obligatory absence of mussels reduces the effectiveness of the IMTA system. As expected, larger-sized IMTA systems have higher production rates and as a result higher percentage of nutrient removal. Finally, bivalve harvesting helps to remove the carbon that is trapped in their shells, contributing to the mitigation of processes related to climate change, such as the acidification of the oceans.

Summary: Staphylococcus aureus can lead to chronic infections and abscesses in internal organs including kidneys, which are associated with the expansion of myeloid-derived suppressor cells (MDSCs) and their suppressive effect on T cells. Here, we developed a mathematical model of chronic S. aureus infection that incorporates the T-cell suppression by MDSCs and suggests therapeutic strategies for S. aureus clearance. A therapeutic protocol with heat-killed S. aureus (HKSA) was quantified in silico and tested in vivo. Contrary to the conventional administration of heat-killed bacteria as vaccination prior to infection, we administered HKSA as treatment in chronically infected hosts. Our treatment eliminated S. aureus in kidneys of all chronically S. aureus-infected mice, reduced MDSCs, and reversed T-cell dysfunction by inducing acute inflammation during ongoing, chronic infection. This study is a guideline for a treatment protocol against chronic S. aureus infection and renal abscesses by repurposing heat-killed treatments, directed by mathematical modeling.

Alginate is a biocompatible and industrially relevant polysaccharide that derives many of its important properties from the charged carboxylate groups within its polyuronic acid backbone. The design and inclusion of isosteric replacements for these carboxylates would underpin provision of new oligo-/polysaccharide materials with alternate physicochemical properties. Presented herein is our synthesis of mannuronic acid building blocks, appropriately modified at the carboxylate C6 position with a bioisosteric tetrazole. Thioglycosides containing a protected C6-tetrazole are accessed from a C6-nitrile, through dipolar cycloaddition using NaN3 with n-Bu2SnO. We also demonstrate access to orthogonally C4-protected donors, suitable for iterative oligosaccharide synthesis. The development of these building blocks is showcased to access anomeric 3-aminopropyl- and 1-phosphate free sugars containing this non-native motif.

Muscle spindles are encapsulated sensory organs found in most of our muscles. Prevalent models of sensorimotor control assume the role of spindles is to reliably encode limb posture and movement. Here, I argue that the traditional view of spindles is outdated. Spindle organs can be tuned by spinal γ motor neurons that receive top-down and peripheral input, including from cutaneous afferents. A new model is presented, viewing γ motor activity as an intermediate coordinate transformation that allows multimodal information to converge on spindles, creating flexible coordinate representations at the level of the peripheral nervous system. That is, I propose that spindles play a unique overarching role in the nervous system: that of a peripheral signal-processing device that flexibly facilitates sensorimotor performance, according to task characteristics. This role is compatible with previous findings and supported by recent studies with naturalistically active humans. Such studies have so far shown that spindle tuning enables the independent preparatory control of reflex muscle stiffness, the selective extraction of information during implicit motor adaptation, and for segmental stretch reflexes to operate in joint space. Incorporation of advanced signal-processing at the periphery may well prove a critical step in the evolution of sensorimotor control theories.

Abstract Between March and April 2020, Cyprus and Greece health authorities enforced three escalated levels of public health interventions to control the COVID-19 pandemic. We quantified compliance of 108 asthmatic schoolchildren (53 from Cyprus, 55 from Greece, mean age 9.7 years) from both countries to intervention levels, using wearable sensors to continuously track personal location and physical activity. Changes in ‘fraction time spent at home’ and ‘total steps/day’ were assessed with a mixed-effects model adjusting for confounders. We observed significant mean increases in ‘fraction time spent at home’ in Cyprus and Greece, during each intervention level by 41.4% and 14.3% (level 1), 48.7% and 23.1% (level 2) and 45.2% and 32.0% (level 3), respectively. Physical activity in Cyprus and Greece demonstrated significant mean decreases by − 2,531 and − 1,191 (level 1), − 3,638 and − 2,337 (level 2) and − 3,644 and − 1,961 (level 3) total steps/day, respectively. Significant independent effects of weekends and age were found on ‘fraction time spent at home’. Similarly, weekends, age, humidity and gender had an independent effect on physical activity. We suggest that wearable technology provides objective, continuous, real-time location and activity data making possible to inform in a timely manner public health officials on compliance to various tiers of public health interventions during a pandemic.

Abstract Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases’ responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Benthic–pelagic coupling studies have shown that the response of the benthic system to eutrophication is subject to complex nonlinear dynamics with specific thresholds beyond which abrupt changes in the response of the ecosystem occur and time lags between inputs and responses. The “HYPOXIA: Benthic–pelagic coupling and regime shifts” project aimed to investigate how nutrient input in the water column results in ecological processes of eutrophication, which may lead to significant, irreversible changes in the eastern Mediterranean marine ecosystems within a short period of time. The project included analysis of historical water and benthic data, field sampling, and mesocosm experiments. From the project results, it can be concluded that nutrient inputs are quickly capitalized by small phytoplankton species in the water column resulting in the bloom of specific species with high nutrient uptake capabilities. When Eutrophic Index values (calculated using nutrient and chlorophyll-a concentrations) cross the moderate-to-poor threshold, the precipitating organic matter can cause observable effects on the benthic system. Depending on eutrophication intensity and persistence, the effects can start from microbenthos, meiofauna, and macrofauna increase in abundance and biomass to significant changes in the community structure. The latter includes the proliferation of macrofaunal opportunistic species, an increase in deposit feeders, and the high risk of ecosystem quality degradation. However, contrary to other regions of the world, no water hypoxia or benthic dead zones were observed as chlorophyll-a and O2 concentrations showed a positive correlation. This is caused by the high photosynthetic activity of the phytoplankton and microphytobenthos, the increased bioturbation of macrofauna, and the increased abundance of sediment deposit-feeding species, which quickly consume the excess organic matter. Eastern Mediterranean coastal ecosystems show high resilience to the adverse effects of eutrophication, preventing hypoxia and azoic conditions when eutrophication is the only source of environmental disturbance.

Attachment is an innate human relational mechanism that develops progressively from early childhood, influences individuals' representations and behaviors, shapes relationships, and affects the social and cultural environment. Parental bonding refers to the ability of parents to be emotionally and behaviorally available to the child during infancy. Attachment style refers to the individual's relational attitude in close relationships that influences adult love, bonding, handling relationships, and social exploration. The role of intergenerational, cultural and developmental factors influencing the relationship between the attachment style in adulthood and the parental bonding style recalled during childhood has been debated. This study explores the relationships between recalled parental bonding, adult attachment style, and cultural background in a sample of Spanish, Italian, and Japanese adults using a cross-sectional and cross-cultural design. For this purpose, the validated versions of the Experience in Close Relationship Scale and the Parental Bonding Instrument were administered to a non-clinical population of three hundred and five participants in the three countries. Results show that the most frequent adult attachment style is the secure style, followed by the dismissing-avoidant, the preoccupied, and the fearful-avoidant style. The dismissing-avoidant style was the most frequent insecure attachment style in the Japanese sample whereas the preoccupied style was the most frequent insecure attachment style in the Italians and Spaniards. Japanese are more anchored to the memory of maternal and paternal overprotection, which is related to more avoidance in actual close relationships. Spaniard's current relationships are mildly independent of recalled parental bonding, showing an association between lower current avoidance to primary parental care. In the Italian sample, there is no significant relationship between current adult close relationships and recalled parental bonding. These results suggest that different cultural models influence adult attachment representations differently, in terms of the weight placed on attachment-related avoidance, attachment-related anxiety, care, and overprotection in infant and adult relationships.

Attachment is an innate human relational mechanism that develops progressively from early childhood, influences individuals’ representations and behaviors, shapes relationships, and affects the social and cultural environment. Parental bonding refers to the ability of parents to be emotionally and behaviorally available to the child during infancy. Attachment style refers to the individual’s relational attitude in close relationships that influences adult love, bonding, handling relationships, and social exploration. The role of intergenerational, cultural and developmental factors influencing the relationship between the attachment style in adulthood and the parental bonding style recalled during childhood has been debated. This study explores the relationships between recalled parental bonding, adult attachment style, and cultural background in a sample of Spanish, Italian, and Japanese adults using a cross-sectional and cross-cultural design. For this purpose, the validated versions of the Experience in Close Relationship Scale and the Parental Bonding Instrument were administered to a non-clinical population of three hundred and five participants in the three countries. Results show that the most frequent adult attachment style is the secure style, followed by the dismissing-avoidant, the preoccupied, and the fearful-avoidant style. The dismissing-avoidant style was the most frequent insecure attachment style in the Japanese sample whereas the preoccupied style was the most frequent insecure attachment style in the Italians and Spaniards. Japanese are more anchored to the memory of maternal and paternal overprotection, which is related to more avoidance in actual close relationships. Spaniard’s current relationships are mildly independent of recalled parental bonding, showing an association between lower current avoidance to primary parental care. In the Italian sample, there is no significant relationship between current adult close relationships and recalled parental bonding. These results suggest that different cultural models influence adult attachment representations differently, in terms of the weight placed on attachment-related avoidance, attachment-related anxiety, care, and overprotection in infant and adult relationships.

Accounting more than 3,700 described species, Oniscidea is the largest and at the same time the only terrestrial isopod suborder inhabiting almost all terrestrial biomes. Despite the great effort dedicated on describing taxonomic diversity of Oniscidea, mainly employing morphology, there is still a considerable number of species/genera of uncertain generic/familiar assignment. Based on different morphological characters, alternative evolutionary relationships have been proposed to describe the diversity of Oniscidea at different phylogenetic levels. Accumulating morphological and genetic data are repeatedly challenging the monophyly of established taxa, undermining the validity of several morphological characters traditionally used in terrestrial isopod taxonomy, leading to often revisions of the current taxonomy of the Oniscidea . The use of genetic data facilitates the efforts to reconstruct the complex evolutionary history of the focal group by providing important data for the identification, delimitation, and description of species. The proposed protocol with universal PCR conditions and primers was used to successfully amplify COI, 16S, 28S and NAK loci in diverse Oniscidea taxa. The application of this protocol is anticipated to facilitate the generation of new genetic data and hence promote scientific research in Isopoda taxonomy, evolution, ecology, and other related fields.

Background: Augmented reality (AR) and artificial intelligence (AI) are highly disruptive technologies that have revolutionised practices in a wide range of domains, including the security sector. Several law enforcement agencies (LEAs) employ AI in their daily operations for forensics and surveillance. AR is also gaining traction in security, particularly with the advent of affordable wearable devices. Equipping police officers with the tools to facilitate an elevated situational awareness (SA) in patrolling and tactical scenarios is expected to improve LEAs’ safety and capacity to deliver crucial blows against terrorist and/or criminal threats. Methods: In this paper we present DARLENE, an ecosystem incorporating novel AI techniques for activity recognition and pose estimation tasks, combined with a wearable AR framework for visualization of the inferenced results via dynamic content adaptation according to the wearer’s stress level and operational context. The concept has been validated with end-users through co-creation workshops, while the decision-making mechanism for enhancing LEAs’ SA has been assessed with experts. Regarding computer vision components, preliminary tests of the instance segmentation method for humans’ and objects’ detection have been conducted on a subset of videos from the RWF-2000 dataset for violence detection, which have also been used to test a human pose estimation method that has so far exhibited impressive results, constituting the basis of further developments in DARLENE. Results: Evaluation results highlight that target users are positive towards the adoption of the proposed solution in field operations, and that the SA decision-making mechanism produces highly acceptable outcomes. Evaluation of the computer vision components yielded promising results and identified opportunities for improvement. Conclusions: This work provides the context of the DARLENE ecosystem and presents the DARLENE architecture, analyses its individual technologies, and demonstrates preliminary results, which are positive both in terms of technological achievements and user acceptance of the proposed solution.

Marine benthic ecosystems face well-documented changes as a result of human activities. Describing these changes is important for predicting ecosystem functioning. In this context, long-term changes in soft-bottom macrofaunal communities after a quarter of a century were studied in the south Aegean Sea with the purpose of investigating whether temporal changes in taxa diversity are accompanied by changes in functional diversity, and secondly to determine the main mechanisms driving these changes (i.e., deterministic versus stochastic processes). To achieve this, a large data set that included species abundance data collected in 1990 and 2014 from several sampling sites along a transect line was used. A biological trait analysis (BTA) was conducted to determine the species functional roles. The results revealed a decline in taxonomic alpha and beta diversity metrics between 1990 and 2014, a difference that was also reflected in functional richness, partially in functional redundancy, but not in functional composition. The stability of functional composition indicated that replacements of functionally similar taxa may occur, ensuring the resilience of the ecosystem to provide goods and services. Finally, the comparison of co-occurrence and functional networks for 1990 indicated a non-differentiation with the null model and, it was not possible to determine if the benthic community was structured due to stochastic processes (e.g., dispersal, natural phenomena) or an overlap of deterministic processes (e.g., niche-filtering, competition). In contrast, the comparison of networks for 2014 pointed out that environmental conditions have acted as a major filter on species distribution.

[This corrects the article DOI: 10.1371/journal.pone.0060674.].

Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2’s unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant although most other diamidine drugs are excluded. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family.

Activin A functions in BMP signaling in two ways: it either engages ACVR1B to activate Smad2/3 signaling or binds ACVR1 to form a non-signaling complex (NSC). Although the former property has been studied extensively, the roles of the NSC remain unexplored. The genetic disorder fibrodysplasia ossificans progressiva (FOP) provides a unique window into ACVR1/Activin A signaling because in that disease Activin can either signal through FOP-mutant ACVR1 or form NSCs with wild-type ACVR1. To explore the role of the NSC, we generated ‘agonist-only’ Activin A muteins that activate ACVR1B but cannot form the NSC with ACVR1. Using one of these muteins, we demonstrate that failure to form the NSC in FOP results in more severe disease pathology. These results provide the first evidence for a biological role for the NSC in vivo and pave the way for further exploration of the NSC’s physiological role in corresponding knock-in mice.

Excessive primary productivity due to nutrient inputs is a potential problem in coastal areas when resulting in high organic matter sedimentation rates. Microphytobenthos and heterotrophic bacteria are two components of the benthic ecosystem that contribute to nutrient cycling and decomposition of organic matter. In this context, the effects of nutrient addition and the associated in situ produced organic matter on microphytobenthos community composition and benthic bacterial viability were assessed in a mesocosm experiment for 58 days. The experimental setup included triplicate mesocosms filled with sediment and water under three levels of nutrient addition (“control,” “low,” and “high”). Benthic algal community composition was assessed using chemotaxonomy and bacterial viability was estimated using flow cytometry and a double-staining protocol. Multivariate analysis detected a significant effect of treatment and time on microphytobenthic community composition indicating a difference between control and low mesocosms and also between low and high treatments at Days 12 and 24 of the experiment. Nonetheless, microphytobenthos implied high resistance and redundancy of benthic algae to disturbance as all three treatments showed no significant difference in community structure between Days 0 and 58. Bacterial viability responded quickly to the high nutrient addition and was significantly lower than in the “control” and “low” treatments at Days 6 and 12. Both pelagic and benthic environmental variables were correlated to these changes in benthic community.

The alpha/beta-Hydrolases (ABH) are a structural class of proteins that are found widespread in nature and includes enzymes that can catalyze various reactions in different substrates. The catalytic versatility of the ABH fold enzymes, which has been a valuable property in protein engineering applications, is based on a similar acid-base-nucleophile catalytic mechanism. In our research, we are concerned with the structure that surrounds the key units of the catalytic machinery, and we have previously found conserved structural organizations that coordinate the catalytic acid, the catalytic nucleophile and the residues of the oxyanion hole. Here, we explore the architecture that surrounds the catalytic histidine at the active sites of enzymes from 40 ABH fold families, where we have identified six conserved interactions that coordinate the catalytic histidine next to the catalytic acid and the catalytic nucleophile. Specifically, the catalytic nucleophile is coordinated next to the catalytic histidine by two weak hydrogen bonds, while the catalytic acid is directly involved in the coordination of the catalytic histidine through by two weak hydrogen bonds. The imidazole ring of the catalytic histidine is coordinated by a CH-π contact and a hydrophobic interaction. Moreover, the catalytic triad residues are connected with a residue that is located at the core of the active site of ABH fold, which is suggested to be the fourth member of a "structural catalytic tetrad". Besides their role in the stability of the catalytic mechanism, the conserved elements of the catalytic site are actively involved in ligand binding and affect other properties of the catalytic activity, such as substrate specificity, enantioselectivity, pH optimum and thermostability of ABH fold enzymes. These properties are regularly targeted in protein engineering applications, and thus, the identified conserved structural elements can serve as potential modification sites in order to develop ABH fold enzymes with altered activities.

Given the great importance of lakes in Earth’s environment and human life, continuous water quality (WQ) monitoring within the frame of the Water Framework Directive (WFD) is the most crucial aspect for lake management. In this study, Earth Observation (EO) data from Landsat 7 Enhanced Thematic Mapper Plus (ETM+) and Landsat 8 Operational Land Imager (OLI) sensors have been combined with co-orbital in situ measurements from 50 lakes located in Greece with the main objective of delivering robust WQ assessment models. Correlation analysis among in situ co-orbital WQ data (Chlorophylla, Secchi depths, Total phosphorus-TP-) contributed to distinguishing their inter-relationships and improving the WQ models’ accuracy. Subsequently, stepwise multiple regression analysis (MLR) of the available TP and Secchi depth datasets was implemented to explore the potential to establish optimal quantitative models regardless of lake characteristics. Then, further MLR analysis concerning whether the lakes are natural or artificial was conducted with the basic aim of generating different remote sensing derived models for different types of lakes, while their combination was further utilized to assess their trophic status. Correlation matrix results showed a high and positive relationship between TP and Chlorophyll-a (0.85), whereas high negative relationships were found between Secchi depth with TP (−0.84) and Chlorophyll-a (−0.83). MLRs among Landsat data and Secchi depths resulted in 3 optimal models concerning the assessment of Secchi depth of all lakes (Secchigeneral; R = 0.78; RMSE = 0.24 m), natural (Secchinatural; R = 0.95; RMSE = 0.14 m) and artificial (Secchiartificial; R = 0.62; RMSE = 0.1 m), with reliable accuracy. Study findings showed that TP-related MLR analyses failed to deliver a statistically acceptable model for the reservoirs; nevertheless, they delivered a robust TPgeneral (R = 0.71; RMSE = 1.41 mg/L) and TPnatural model (R = 0.93; RMSE = 1.43 mg/L). Subsequently, trophic status classification was conducted herein, calculating Carlson’s Trophic State Index (TSI) initially throughout all lakes and then oriented toward natural-only and artificial-only lakes. Those three types of TSI (general, natural, artificial) were calculated based on previously published satellite-derived Chlorophyll-a (Chl-a) assessment models and the hereby specially designed WQ models (Secchi depth, TP). The higher deviation of satellite-derived TSI values in relation to in situ ones was detected in reservoirs and shallower lakes (mean depth < 5 m), indicating noticeable divergences among natural and artificial lakes. All in all, the study findings provide important support toward the perpetual WQ monitoring and trophic status prediction of Greek lakes and, by extension, their sustainable management, particularly in cases when ground truth data is limited.

The ecological assessment of all surface water bodies in Europe according to the Water Framework Directive involves the monitoring of biological, physicochemical and hydromorphological quality elements. For the hydromorphological assessment in particular, there are numerous methods that have been developed and adopted by EU member countries. With this study, we compared three different methods (River Habitat Survey, Morphological Quality Index and River Hydromorphology Assessment Technique) applied in 122 river reaches that are part of the National Monitoring Network of Greece. The main objectives were (a) to identify whether different assessment systems provide similar classifications of hydromorphological status and (b) to distinguish strengths and weaknesses associated with the implementation of each method. Our results show that the River Hydromorphology Assessment Technique (RHAT) and the Morphological Quality Index (MQI) resulted in the same classification for 58% of the studied reaches, while 34% of the remaining cases differed by only one quality class. Correlations between the two indices per river type (ICT) showed that the two indices were strongly correlated for water courses located at low altitudes. Concerning the HMS index of the River Habitat Survey (RHS), which is an index that reflects the overall hydromorphological pressure, it showed larger differences with the other two indices, mainly because it classified more sites as “Poor” and “Bad” quality classes. Based on our results, we recommend that the two indices, RHAT and MQI, can be implemented complementary to the RHS for providing a rather easy and quick assessment of the overall hydromorphological status, at least until a national hydromorphological database is compiled that will allow for the proper adaptation of the Habitat Quality Assessment (HQA) index.

There is a growing global awareness about the impacts of climate change on cultural and natural heritage sites. In Greece—a homeland of important historical and cultural resources—archaeological sites are vulnerable to climate change-related flood events. In order to investigate the flood risk of the archaeological site of Ancient Messene under different climate change projections, a physically-based hydrological model was implemented and six climate change scenarios were examined. Additionally, the effectiveness of a soft structural nature-based solution adaption plan was evaluated. Based on the results, the archaeological site of Ancient Messene is shielded against small or larger flood events and only in case of extreme precipitation events is the area likely to be at risk. This flood risk can be further eliminated after implementing the soft structural nature-based solution adaptation plan proposed. Nature-based solutions provide a cost-effective alternative approach for flood risk reduction and climate change adaptation, with minimum possible disturbance, while hydrological modeling, even in case of data scarcity, constitute a valuable tool for flood risk estimation and adaptation plan management. Nature-based solutions seems to be most effective against small or medium precipitation events, and to limit the damages of extreme events. Their benefits for flood adaptation should not be underestimated.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3

Exploring the plasma processes in the pre-plasma state that lead to instabilities is challenging. Here the authors probe the evolution of the plasma phase change and the instabilities in plasma created by an exploding copper wire in Z-pinch geometry using shadowgraphy.

Water resources, especially riverine ecosystems, are globally under qualitative and quantitative degradation due to human-imposed pressures. High-temporal-resolution data obtained from automatic stations can provide insights into the processes that link catchment hydrology and streamwater chemistry. The scope of this paper was to investigate the statistical behavior of high-frequency measurements at sites with known hydromorphological and pollution pressures. For this purpose, hourly time series of water levels and key water quality indicators (temperature, electric conductivity, and dissolved oxygen concentrations) collected from four automatic monitoring stations under different hydromorphological conditions and pollution pressures were statistically elaborated. Based on the results, the hydromorphological conditions and pollution pressures of each station were confirmed to be reflected in the results of the statistical analysis performed. It was proven that the comparative use of the statistics and patterns of the water level and quality high-frequency time series could be used in the interpretation of the current site status as well as allowing the detection of possible changes. This approach can be used as a tool for the definition of thresholds, and will contribute to the design of management and restoration measures for the most impacted areas.

Riparian zones play an important role in the ecological stability of rivers. In particular, the quality of the riparian vegetation is a significant component of the hydromorphological status. In Europe, the QBR index (Qualitat del Bosc de Ribera) and the River Habitat Survey (RHS) are commonly used for the qualitative assessment of the riparian vegetation. In this study, we estimated the QBR index and the Riparian Quality index, which is derived from the RHS method, for 123 river reaches of the National Monitoring Network of Greece. Our field work included the completion of RHS and QBR protocols, as well as the use of Unmanned Aerial Vehicles (UAVs). The aim of this study is to assess the riparian vegetation status and to identify linkages with the dominant land uses within the catchment. Correlation analysis was used to identify the relationships between hydromorphological alterations and the degradation of the riparian vegetation, as well as their connection to land uses in the catchment area. Our results highlighted severe modifications of the riparian vegetation for the majority of the studied reaches. We also showed a differentiation of the QBR with respect to changes in the altitude and the land uses in the catchment area. Overall QBR reflects the variation in the riparian vegetation quality better than RQI. Our findings constitute an assessment of the status of the riparian zones in Greek rivers and set the basis for further research for the development of new and effective tools for a rapid quality assessment of the riparian zones.

The monitoring of surface waters is of fundamental importance for their preservation under good quantitative and qualitative conditions, as it can facilitate the understanding of the actual status of water and indicate suitable management actions. Taking advantage of the experience gained from the coordination of the national water monitoring program in Greece and the available funding from two ongoing infrastructure projects, the Institute of Inland Waters of the Hellenic Centre for Marine Research has developed the first homogeneous real-time network of automatic water monitoring across many Greek rivers. In this paper, its installation and maintenance procedures are presented with emphasis on the data quality checks, based on values range and variability tests, before their online publication and dissemination to end-users. Preliminary analyses revealed that the water pH and dissolved oxygen (DO) sensors and produced data need increased maintenance and quality checks respectively, compared to the more reliably recorded water stage, temperature (T) and electrical conductivity (EC). Moreover, the data dissemination platform and selected data visualization options are demonstrated and the need for both this platform and the monitoring network to be maintained and potentially expanded after the termination of the funding projects is highlighted.

River flow alterations, caused by climate variability/change and intense anthropogenic uses (e.g., flow regulation by dams) are considered among the main global challenges of which hydrologists should be dealing with. For the purpose of this study, environmental flow and potential hydrological alterations are made for the extended Drin river basin, with limited historical hydrological information available. To overcome this limitation environmental flow assessment is made using simulated streamflow data from a watershed hydrological model. Descriptive statistics applied to streamflow values indicate that median monthly flows with no anthropogenic uses are consistently greater than those with anthropogenic uses by 0–37.4 m3/s in all subbasins. Moreover, an investigation of potential climate variability/change impact on river flow regime is made using streamflow simulations from a global hydrological model. Results indicate that hydrologic alteration is intense between nonregulated and regulated streamflow conditions. More specifically, for all Global Circulation Models and Regional Climate Models combinations, and both regulated and unregulated streamflow conditions, the minimum discharge values had statistically significant decreasing trends, except one combination (RCP 4.5–RCA4/ECEARTH) for unregulated conditions. Finally, results from this preliminary analysis could enhance the necessary conversations among all relevant stakeholders to discuss and decide on sustainable water resources management issues for the development of a Drin Basin Management Plan in the future.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Assessing chlorophyll-a (Chl-a) pigments in complex inland water systems is of key importance as this parameter constitutes a major ecosystem integrity indicator. In this study, a methodological framework is proposed for quantifying Chl-a pigments using Earth observation (EO) data from Landsat 7 Enhanced Thematic Mapper Plus (ETM+) and 8 Operational Land Imager (OLI) sensors. The first step of the methodology involves the implementation of stepwise multiple regression (MLR) analysis of the available Chl-a dataset. Then, principal component analysis (PCA) is performed to explore Greek lakes’ potential interrelationships based on their Chl-a values in conjunction with certain criteria: their characteristics (artificial/natural), typology, and climatic type. Additionally, parameters such as seasonal water sampling and the date difference between sampling and satellite overpass are taken into consideration. Next, is implemented a stepwise multiple regression analysis among different groups of cases, formed by the criteria indicated from the PCA itself. This effort aimed at exploring different remote sensing-derived Chl-a algorithms for various types of lakes. The practical use of the proposed approach was evaluated in a total of 50 lake water bodies (natural and artificial) from 2013–2018, constituting the National Lake Network Monitoring of Greece in the context of the Water Framework Directive (WFD). All in all, the results evidenced the suitability of Landsat data when used with the proposed technique to estimate log-transformed Chl-a. The proposed scheme resulted in the development of models separately for natural (R = 0.78; RMSE = 1.3 μg/L) and artificial lakes (R = 0.76; RMSE = 1.29 μg/L), while the model developed without criteria proved weaker (R = 0.65; RMSE = 1.85 μg/L) in comparison to the other ones examined. The methodological framework proposed herein can be used as a useful resource toward a continuous monitoring and assessment of lake water quality, supporting sustainable water resources management.

The Water Framework Directive (WFD) requires from member states to monitor hydromorphological features of rivers in order to assess their ecological quality. Thus, numerous hydromorphological assessment methods have been developed with most of them focusing on the dynamics of hydrology, geomorphology and riparian zone extent. Within the scope of this study, we assessed the hydromorphological features of 106 river reaches distributed among thirteen WFD River Basin Districts (RBDs) to identify the main drivers of hydromorphological perturbation at a national scale. The studied reaches reflect a wide range of natural variability as they include various types of watercourses extending from lowlands to mid-altitude and mountainous systems. We employed the River Habitat Survey (RHS), and we recorded hydromorphological features and modifications in both banks and the channel bed along 500 m for each reach. Then, the Habitat Modification Score (HMS) and the individual sub-scores that indicate the extent of specific modifications (e.g., bridges, fords, weirs, bank reprofiling, bank reinforcement, etc.) were calculated in order to a) assess the severity of the total artificial modification and b) to highlight the most common and severe causes of overall alteration. The results showed that alterations such as reprofiling and reinforcement of banks contributed the most to the total HMS followed by the presence of fords and bridges. Particularly, the bank alterations indicate a serious deterioration of the longitudinal profile of the reaches, while the occurrence of many fords and bridges is the main cause for perturbations that affect locally the stream cross-sectional profile. Overall, these results compile a first nationwide assessment of the hydromorphological status of Greek rivers in line with the WFD and set the basis for further research that will focus on the diversity of stream habitat features as a measure for the overall ecological quality.

A benthic-pelagic mesocosm experiment was performed to study how the benthic macrofaunal community responds to a eutrophication gradient. The novel experimental setup allowed the induction of an eutrophication gradient in the water column and the detailed documentation of the response of the benthos in terms of biodiversity and ecosystem processes. Nine mesocosms were deployed in the facilities of the Hellenic Center for Marine Research in Crete in the eastern Mediterranean. The mesocosms were 4 m deep, contained 1.5 m3 coastal water, and included 85 liters of undisturbed sediment at the bottom. No water or sediment exchange was allowed. The experimental design included a Control and two eutrophication levels (Low and High) for the 58-day duration of the experiment. Macrofaunal samples were collected at the end of the experiment from each mesocosm and compared to the ones collected at the beginning of the experiment from the sediment collection area. Results show that the High eutrophication treatment differed significantly from the Control and Low treatments in terms of macrofaunal species composition, diversity, ecological status and ecosystem processes. The increased availability of organic matter in the sediment caused differences in macrofaunal community structure by favoring deposit-feeding species with high bioturbation ability, which significantly increased their abundance. The increased bioturbation potential of the new community combined with the high organic matter consumption contributed to the oxygenation of the sediment within the mesocosm, preventing the creation of hypoxic conditions in the sediment and maintaining ecosystem health despite the highly eutrophic conditions and significant changes in sediment geochemical variables. In the oligotrophic eastern Mediterranean, healthy benthic ecosystems may use existing ecosystem processes to “buffer” the negative effects caused by eutrophication.

The effect of episodicity of Saharan dust deposition on the pelagic microbial food web was studied in the oligotrophic Eastern Mediterranean by means of a mesocosm experiment in May 2014. Two different treatments in triplicates (addition of natural Saharan dust in a single-strong pulse or in three smaller consecutive doses of the same total quantity), and three unamended controls were employed; chemical and biological parameters were measured during a 10-day experiment. Temporal changes in primary (PP) and bacterial (BP) production, chlorophyll a (Chl a) concentration and heterotrophic bacteria, Synechococcus and mesozooplankton abundance were studied. The results suggested that the auto- and hetero-trophic components of the food web (at least the prokaryotes) were enhanced by the dust addition (and by the nitrogen and phosphorus added through dust). Furthermore, a 1-day delay was observed for PP, BP, and Chl a increases when dust was added in three daily doses; however, the maximal values attained were similar in the two treatments. Although, the effect was evident in the first osmotrophic level (phytoplankton and bacteria), it was lost further up the food web, masked under the impact of grazing exerted by predators such as heterotrophic flagellates, ciliates and dinoflagellates. This was partly proved by two dilution experiments. This study demonstrates the important role of atmospheric deposition and protist grazing when evaluating the effect on oligotrophic systems characterized by increased numbers of trophic levels.

BACKGROUND:Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE:To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. DESIGN:We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. RESULTS:Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. CONCLUSIONS:These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. We tested the hypothesis here whether the cumulative effect of glucose raising SNPs, assessed via a score, is associated with glucose levels. A total of 1,434 participants of Greek descent from the THISEAS study and 1,160 participants form the GOMAP study were included in this analysis. We developed a genetic risk score (GRS), based on the known glucose-raising loci, in order to investigate the cumulative effect of known glucose loci on glucose levels. In the THISEAS study, the GRS score was significantly associated with increased glucose levels (mmol/L) (β ± SE: 0.024 ± 0.004, P = 8.27e-07). The effect of the genetic risk score was also significant in the GOMAP study (β ± SE: 0.011 ± 0.005, P = 0.031). In the meta-analysis of the two studies both scores were significantly associated with higher glucose levels GRS: β ± SE: 0.019 ± 0.003, P = 1.41e-09. Also, variants at the SLC30A8, PROX1, MTNR1B, ADRA2A, G6PC2, LPIN3 loci indicated nominal evidence for association with glucose levels (p < 0.05). We replicate associations of the established glucose raising variants in the Greek population and confirm directional consistency of effects (binomial sign test p = 6.96e-05). We also demonstrate that the cumulative effect of the established glucose loci yielded a significant association with increasing glucose levels.

Newborns delivered late-preterm (between 340/7 and 366/7 weeks of gestation) are at increased risk of respiratory distress syndrome (RDS). Polymorphisms within the surfactant protein (SP) A and B gene have been shown to predispose to RDS in preterm neonates. The aim of this study was to investigate whether specific SP-A and/or SP-B genetic variants are also associated with RDS in infants born late-preterm.This prospective cross-sectional study included 56 late-preterm infants with and 60 without RDS. Specific SP-A1/SP-A2 haplotypes and SP-B Ile131Thr polymorphic alleles were determined in blood specimens using polymerase-chain-reaction and DNA sequencing.The SP-A1 6A4 and the SP-A2 1A5 haplotypes were significantly overrepresented in newborns with RDS compared to controls (OR 2.86, 95%CI 1.20-6.83 and OR 4.68, 95%CI 1.28-17.1, respectively). The distribution of the SP-B Ile131Thr genotypes was similar between the two late-preterm groups. Overall, the SP-A1 6A4 or/and SP-A2 1A5 haplotype was present in 20 newborns with RDS (35.7%), resulting in a 4.2-fold (1.60-11.0) higher probability of RDS in carriers. Multivariable regression analysis revealed that the effect of SP-A1 6A4 and SP-A2 1A5 haplotypes was preserved when adjusting for known risk or protective factors, such as male gender, smaller gestational age, smaller weight, complications of pregnancy, and administration of antenatal corticosteroids.Specific SP-A genetic variants may influence the susceptibility to RDS in late-preterm infants, independently of the effect of other perinatal factors.

In-situ monitoring of lake water quality in synergy with satellite remote sensing represents the latest scientific trend in many water quality monitoring programs worldwide. This study investigated the suitability of the Operational Land Imager (OLI) instrument onboard the Landsat 8 satellite platform in accurately estimating key water quality parameters such as chlorophyll-a and nutrient concentrations. As a case study the largest freshwater body of Greece (Trichonis Lake) was used. Two Landsat 8 images covering the study site were acquired on 30 October 2013 and 30 August 2014 respectively. Near concurrent in-situ observations from two water sampling campaigns were also acquired from 22 stations across the lake under study. In-situ measurements (nutrients and chlorophyll-a concentrations) were statistically correlated with various spectral band combinations derived from the Landsat imagery of year 2014. Subsequently, the most statistically promising predictive models were applied to the satellite image of 2013 and validation was conducted using in-situ data of 2013 as reference. Results showed a relatively variable statistical relationship between the in-situ and reflectances (R logchl-a: 0.58, R NH4+: 0.26, R chl-a: 0.44). Correlation coefficient (R) values reported of up to 0.7 for ammonium concentrations and also up to 0.5 and up to 0.4 for chl-a concentration and chl-a concentrations respectively. These results represent a higher accuracy of Landsat 8 in comparison to its predecessors in the Landsat satellites series, as evidenced in the literature. Our findings suggest that Landsat 8 has a promising capability in estimating water quality components in an oligotrophic freshwater body characterized by a complete absence of any quantitative, temporal and spatial variance, as is the case of Trichonis lake. Yet, even with the presence of a lot of ground information as was the case in our study, a quantitatively accurate estimation of water quality constituents in coastal/inland waters remains a great challenge. The launch of sophisticated spaceborne sensing systems, such as that of Landsat 8, can assist in improving our ability to estimate freshwater lake properties from space.

PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

The role of CD64 in late onset sepsis (LOS) in preterm infants has been described in several studies. Aim of this study was to investigate whether CD64 expression is increased in the days before clinical manifestation of LOS.Patients with birth weight below 1,500 g were eligible for study participation. During routine blood sampling CD64 index was determined between day of life 4 and 28. Patients were allocated to one of four groups: (1) blood-culture positive sepsis, (2) clinical sepsis, (3) symptoms of infection without biochemical evidence of infection, or (4) patients without suspected infection. Kinetics of CD64 expression were compared during a period before and after the day of infection in the respective groups.50 infants were prospectively enrolled and allocated to each group as follows: group (1) n = 7; group (2) n = 10; group (3) n = 8; and group (4) n = 25. CD64 index was elevated in 57% of patients in group (1) at least two days before infection. In contrast only 20% in the clinical sepsis group and 0% in group (3) had an elevated CD64 index in the days before infection. 10 of the 25 patients in the control group (4) presented increased CD64 index values during the study period.The CD64 index might be a promising marker to detect LOS before infants demonstrate signs or symptoms of infection. However, larger prospective studies are needed to define optimal cut-off values and to investigate the role of non-infectious inflammation in this patient group.

A large data set from the Eastern Mediterranean was analyzed to explore the relationship between seawater column variables and benthic community status. Our results showed a strong quantitative link between the seawater column variables (Chlorophyll a and Eutrophication Index) and various indicators describing benthic diversity and community composition. The percentage of benthic opportunistic species increased significantly in the stations with high trophic status of the seawater column and so did the strength of the coupling between values of seawater column and benthic indicators. The Eutrophication Index threshold level of 0.85, separating the "Bad and Poor" from "Moderate to High" conditions could serve as an acceptable critical value above which there is a readily observable change in benthic community composition.