Metabolomic and high-throughput sequencing analysis—modern approach for the assessment of biodeterioration of materials from historic buildings

Preservation of cultural heritage is of paramount importance worldwide. Microbial colonization of construction materials, such as wood, brick, mortar and stone in historic buildings can lead to severe deterioration. The aim of the present study was to give modern insight into the phylogenetic diversity and activated metabolic pathways of microbial communities colonized historic objects located in the former Auschwitz II-Birkenau concentration and extermination camp in Oświęcim, Poland. For this purpose we combined molecular, microscopic and chemical methods. Selected specimens were examined using Field Emission Scanning Electron Microscopy (FESEM), metabolomic analysis and high-throughput Illumina sequencing. FESEM imaging revealed the presence of complex microbial communities comprising diatoms, fungi and bacteria, mainly cyanobacteria and actinobacteria, on sample surfaces. Microbial diversity of brick specimens appeared higher than that of the wood and was dominated by algae and cyanobacteria, while wood was mainly colonized by fungi. DNA sequences documented the presence of 15 bacterial phyla representing 99 genera including Halomonas, Halorhodospira, Salinisphaera, Salinibacterium, Rubrobacter, Streptomyces, Arthrobacter and 9 fungal classes represented by 113 genera including Cladosporium, Acremonium, Alternaria, Engyodontium, Penicillium, Rhizopus and Aureobasidium. Most of the identified sequences were characteristic of organisms implicated in deterioration of wood and brick. Metabolomic data indicated the activation of numerous metabolic pathways, including those regulating the production of primary and secondary metabolites, for example, metabolites associated with the production of antibiotics, organic acids and deterioration of organic compounds. The study demonstrated that a combination of electron microscopy imaging with metabolomic and genomic techniques allows to link the phylogenetic information and metabolic profiles of microbial communities and to shed new light on biodeterioration processes

First-generation structure-activity relationship studies of 2,3,4,9-tetrahydro-1H-carbazol-1-amines as CpxA phosphatase inhibitors

Genetic activation of the bacterial two-component signal transduction system, CpxRA, abolishes the virulence of a number of pathogens in human and murine infection models. Recently, 2,3,4,9-tetrahydro-1H-carbazol-1-amines were shown to activate the CpxRA system by inhibiting the phosphatase activity of CpxA. Herein we report the initial structure-activity relationships of this scaffold by focusing on three approaches 1) A-ring substitution, 2) B-ring deconstruction to provide N-arylated amino acid derivatives, and 3) C-ring elimination to give 2-ethylamino substituted indoles. These studies demonstrate that the A-ring is amenable to functionalization and provides a promising avenue for continued optimization of this chemotype. Further investigations revealed that the C-ring is not necessary for activity, although it likely provides conformational constraint that is beneficial to potency, and that the (R) stereochemistry is required at the primary amine. Simplification of the scaffold through deconstruction of the B-ring led to inactive compounds, highlighting the importance of the indole core. A new lead compound 26 was identified, which manifests a ∼30-fold improvement in CpxA phosphatase inhibition over the initial hit. Comparison of amino and des-amino derivatives in bacterial strains differing in membrane permeability and efflux capabilities demonstrate that the amine is required not only for target engagement but also for permeation and accumulation in Escherichia coli

The factor structure of the Forms of Self-Criticising/Attacking & Self-Reassuring Scale in thirteen distinct populations

There is considerable evidence that self-criticism plays a major role in the vulnerability to and recovery from psychopathology. Methods to measure this process, and its change over time, are therefore important for research in psychopathology and well-being. This study examined the factor structure of a widely used measure, the Forms of Self-Criticising/Attacking & Self-Reassuring Scale in thirteen nonclinical samples (N = 7510) from twelve different countries: Australia (N = 319), Canada (N = 383), Switzerland (N = 230), Israel (N = 476), Italy (N = 389), Japan (N = 264), the Netherlands (N = 360), Portugal (N = 764), Slovakia (N = 1326), Taiwan (N = 417), the United Kingdom 1 (N = 1570), the United Kingdom 2 (N = 883), and USA (N = 331). This study used more advanced analyses than prior reports: a bifactor item-response theory model, a two-tier item-response theory model, and a non-parametric item-response theory (Mokken) scale analysis. Although the original three-factor solution for the FSCRS (distinguishing between Inadequate-Self, Hated-Self, and Reassured-Self) had an acceptable fit, two-tier models, with two general factors (Self-criticism and Self-reassurance) demonstrated the best fit across all samples. This study provides preliminary evidence suggesting that this two-factor structure can be used in a range of nonclinical contexts across countries and cultures. Inadequate-Self and Hated-Self might not by distinct factors in nonclinical samples. Future work may benefit from distinguishing between self-correction versus shame-based self-criticism.Peer reviewe

Evaluating psychometric properties of the Emotional Eating Scale Adapted for Children and Adolescents (EES-C) in a clinical sample of children seeking treatment for obesity: a case for the unidimensional model.

BackgroundThe Emotional Eating Scale - Adapted for Children and Adolescents (EES-C) assesses children's urge to eat in response to experiences of negative affect. Prior psychometric studies have demonstrated the high reliability, concurrent validity, and test-retest reliability of theoretically defined subconstructs among non-clinical samples of children and adolescents who were primarily healthy weight; however, no psychometric studies exist investigating the EES-C among clinical samples of children with overweight/obesity (OW/OB). Furthermore, studies conducted in different contexts have suggested a discordant number of subconstructs of emotions related to eating. The purpose of this study was to evaluate the validity of the EES-C in a clinical sample of children seeking weight-loss treatment.MethodUsing a hierarchical bi-factor approach, we evaluated the validity of the EES-C to measure a single general construct, a set of two separate correlated subconstructs, or a hierarchical arrangement of two constructs, and determined reliability in a clinical sample of treatment-seeking children with OW/OB aged 8-12 years (N = 147, mean age = 10.4 years.; mean BMI z = 2.0; female = 66%; Hispanic = 32%, White and other = 68%).ResultsComparison of factor-extraction methods suggested a single primary construct underlying EES-C in this clinical sample. The bi-factor indices provided clear evidence that most of the reliable variance in the total score (90.8 for bi-factor model with three grouping factors and 95.2 for bi-factor model with five grouping factors) was attributed to the general construct. After adjusting for relationships with the primary construct, remaining correlations among sets of items did not suggest additional reliable constructs.ConclusionResults suggest that the primary interpretive emphasis of the EES-C among treatment-seeking children with overweight or obesity should be placed on a single general construct, not on the 3- or 5- subconstructs as was previously suggested

The Atapuerca sites and the Ibeas hominids

The Atapuerca railway Trench and Ibeas sites near Burgos, Spain, are cave fillings that include a series of deposits ranging from below the Matuyama/Bruhnes reversal up to the end of Middle Pleistocene. The lowest fossil-bearing bed in the Trench contains an assemblage of large and small Mammals including Mimomys savini, Pitymys gregaloides, Pliomys episcopalis, Crocuta crocuta, Dama sp. and Megacerini; the uppermost assemblage includes Canis lupus, Lynx spelaea, Panthera (Leo) fossilis, Felis sylvestris, Equus caballus steinheimensis, E.c. germanicus, Pitymys subtenaneus, Microtus arvalis agrestis, Pliomys lenki, and also Panthera toscana, Dicerorhinus bemitoechus, Bison schoetensacki, which are equally present in the lowest level. The biostratigraphic correlation and dates of the sites are briefly discussed, as are the paleoclimatic interpretation of the Trench sequences. Stone artifacts are found in several layers; the earliest occurrences correspond to the upper beds containing Mimomys savini. A set of preserved human occupation floors has been excavated in the top fossil-bearing beds. The stone-tool assemblages of the upper levels are of upper-medial Acheulean to Charentian tradition. The rich bone breccia SH, in the Cueva Mayor-Cueva del Silo, Ibeas de Juarros, is a derived deposit, due to a mud flow that dispersed and carried the skeletons of many carnivores and humans. The taxa represented are: Vrsus deningeri (largely dominant), Panthera (Leo) fossilis, Vulpes vulpes, Homo sapiens var. Several traits of both mandibular and cranial remains are summarized. Preliminary attempts at dating suggest that the Ibeas fossil man is older than the Last Interglacial, or oxygen-isotope stage 5

Revisiting the five-facet structure of mindfulness

The current study aimed to replicate the development of the Five-Facet Mindfulness Questionnaire (FFMQ) in a sample of 399 undergraduate students. We factor analyzed the Mindful Attention and Awareness Questionnaire (MAAS), the Freiburg Mindfulness Scale, the Southampton Mindfulness Questionnaire (SMQ), the Cognitive Affective Mindfulness Scale Revised (CAMS-R), and the Kentucky Inventory of Mindfulness Skills (KIMS), but also extended the analysis by including a conceptually related measure, the Philadelphia Mindfulness Scale (PHLMS), and a conceptually unrelated measure, the Langer Mindfulness Scale (LMS). Overall, we found a partial replication of the five-factor structure, with the exception of non-reacting and non-judging which formed a single factor. The PHLMS items loaded as expected with theoretically related factors, whereas the LMS items emerged as separate factor. Finally, we found a new factor that was mostly defined by negatively worded items indicating possible item wording artifacts within the FFMQ. Our conceptual validation study indicates that some facets of the FFMQ can be recovered, but item wording factors may threaten the stability of these facets. Additionally, measures such as the LMS appear to measure not only theoretically, but also empirically different constructs

Sea level and climate changes during OIS 5e in the Western Mediterranean

Palaeontological, geomorphological and sedimentological data supported by isotopic dating on Oxygen Isotopic Stage (OIS) 5e deposits from the Spanish Mediterranean coast, are interpreted with the aim of reconstructing climatic instability in the Northern Hemisphere. Data point to marked climatic instability during the Last Interglacial (OIS 5e), with a change in meteorological conditions and, consequently, in the sedimentary environment. The oolitic facies generated during the first part of OIS 5e (ca. 135 kyr) shift into reddish conglomeratic facies during the second part (ca. 117 kyr). Sea surface Temperature (SST) and salinity are interpreted mainly on the basis of warm Senegalese fauna, which show chronological and spatial differential distribution throughout the Western Mediterranean. Present hydrological and meteorological conditions are used also as modern analogues to reconstruct climatic variability throughout the Last Interglacial, and this variability is interpreted within the wider framework of the North Atlantic record. All the available data indicate an increase in storminess induced by an increase in the influence of northwesterlies, a slight drop of SST in the northern Western Mediterranean, and an important change in meteorological conditions at the end of OIS 5e (117 kyr). These changes correlate well with the decrease in summer insolation and with the climatic instability recorded in North Atlantic high latitudes

Further evidence for a relatively high sea level during the penultimate interglacial: open-system U-series ages from La Marina (Alicante, East Spain)

The elevation and timing of high sea stands during Oxygen Isotope Stage (OIS) 7 are not as well constraíned as those of OIS 5e. Conflictíng values are reported from Medíterranean coastlines, and fossil dating is inaccurate because of ubiquitous open U-series systems. New morphostratigraphic data from La Marina (eastem Spain) supported by open-system U-series coral ages shed light on the maximum sea level duríng OIS 7. Fossil corals (Cladocora Caespitosa) underlying an OIS 5e marine unít yielded U-series ages from 178 ± (0 to 208 ± 1) ka (± 20σ n=7) with an outlier al 240 ± 18 ka. Mean open-system limit ages of 170 ± 10 (minimum age after correction for 234Th-230Th uptake) and 237 ± 20 ka (maximum ase after correction for 238U - 234U uptake) were calculated to have a probable age closer to the minimum value, for an assignment of OlS 7a or 7c. The occurrence of a warn-water "Senegalese" fauna (Strombus bubonius) in OIS5e and OIS 7 marine units confirms the arrival of tropical species to the Mediterranean before the last interglacial periodo Morpho-sedimentological and neotectonic studies suggest that the maximum paleo-sea level during OIS 7c or 7a was a few melers below that of OlS Se

Re-evaluation of the latent structure of common childhood disorders: is there a general psychopathology factor (P-factor)?

In the field of psychopathology, there is high comorbidity between different disorders. Traditionally, support for two broad correlated dimensions of internalizing and externalizing symptoms has consistently emerged for children and adolescents. To date, oblique 2 and 3 first-order factor models (factors for externalizing and internalizing, and fear, distress, and externalizing) and bi-factor models with the corresponding two and three group factors have been suggested for common internalizing and eternalizing child and adolescent disorders. The present study used confirmatory factor analyses to examine the relative support for these models in adolescents (≥ 12 to 18 years; N = 866) and children (6 to < 12 years; N = 1233) and the reliability and convergent and divergent validities of the psychopathology factor (P-factor) and group factors in the optimum bi-factor model. All participants were from a clinic and underwent Diagnostic and Statistical Manual of Mental Disorders, 4th Edition clinical diagnosis. The findings showed that the bi-factor model with two group factors (internalizing and externalizing) was the optimum model for both children and adolescents. For both groups, findings showed relatively higher reliability for the P-factor than the group factors, although the externalizing group factor showed substantial reliability in adolescents, and both the externalizing and internalizing group factors also showed substantial reliability in children. The factors of the optimum bi-factor model also showed good convergent and discriminant validities. The implications for theory and clinical and research practice related to psychopathology are discussed

Blood coagulation and beyond: position paper from the fourth Maastricht consensus conference on thrombosis

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ- specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/ or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of- the- art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i. e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID- 19-associated coagulopathy is revisited.Nephrolog