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Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB 50 ) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC 50 ) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans . Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin’s multipotentiality against these fungal infections.

Annexin A2 (AnxA2) is a cytosolic Ca2+ regulated membrane binding protein that can induce lipid domain formation and plays a role in exocytosis and endocytosis. To better understand the mode of annexin-membrane interaction, we analyzed membrane-bound AnxA2 assemblies by employing a novel 3-armed chemical crosslinker and specific AnxA2 mutant proteins. Our data show that AnxA2 forms crosslinkable oligomers upon binding to membranes containing negatively charged phospholipids. AnxA2 mutants with amino acid substitutions in residues predicted to be involved in lateral protein–protein interaction show compromised oligomer formation, albeit still being capable of binding to negatively charged membranes in the presence of Ca2+. These results suggest that lateral protein–protein interactions are involved in the formation of AnxA2 clusters on a biological membrane.

The study evaluated the preservative potential of Lafoensia replicata Pohl. leaf extracts in cosmetics, highlighting their antioxidant, antimicrobial, and in vitro cytotoxic activities for ethanolic extract prepared by the maceration and tincture method. Total phenol content showed a higher phenol concentration in ethanolic extract and tinctures, and by LC-MS/MS-ESI-QTOF analysis, flavonoids, hydrolyzed tannins, and phenolic acids were identified. The ethanolic extract and tincture showed high antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans (MIC < 50 µg mL−1), high antioxidant activity (EC50 < 50 µg mL−1 in the DPPH method, and results > 450 µmol trolox equivalent in the ABTS and FRAP method), and low cytotoxicity in human keratinocytes (IC50 > 350 µg mL−1). The results suggest these extracts could be an alternative to synthetic preservatives in the cosmetic industry.

Research summary Drawing on the demographic faultline perspective and the concept of attribute‐specific faultlines, we investigate the effect of top management team (TMT) relationship‐related (gender, age, educational level) and task‐related (functional background, tenure) faultline strengths on strategic change. In a panel study (2003–2015), we find that TMT relationship‐related faultline strength (especially educational‐level) negatively influences strategic change whereas TMT task‐related faultline strength positively affects strategic change. Environmental dynamism reduces the negative effect of TMT gender and educational‐level faultline strengths on strategic change while in fact revealing a notable positive effect between TMT age‐faultline strength and strategic change. Additionally, environmental dynamism strengthens the positive effects of task‐related TMT faultline strength on strategic change. We offer theoretical and practical implications to both the demographic faultlines and upper echelons research domains. Managerial summary Top management teams (TMTs) in firms can fracture into subgroups based on demographic characteristics (e.g., age, gender, and education level) as well as based on task‐related characteristics (e.g., functional background, and tenure). We call the former relationship‐related faultlines and the latter task‐related faultlines. We predict and find that stronger relationship based faultlines hinders between subgroup cohesion, reducing TMTs' ability to initiate strategic change. We also predict and find that stronger task‐related faultlines facilitate inter‐subgroup knowledge‐sharing, improving TMTs' ability to initiate strategic change. We find that environmental dynamism reduces the negative effect of most relationship‐related faultlines (except age where this effect is positive) on strategic change, while strengthening the positive effect of task‐related faultline strengths on strategic change. Video 

Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006-2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of -129 g (95% CI: -233, -25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (-248 g; 95% CI: -405, -92 g) compared with those with high intake (-58 g; 95% CI: -206, 90 g). Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.

Mechanisms keeping leukocytes distant of local inflammatory processes in a resting state despite systemic release of inflammatory triggers are a pivotal requirement for avoidance of overwhelming inflammation but are ill defined. Dimers of the alarmin S100A8/S100A9 activate Toll‐like receptor‐4 (TLR4) but extracellular calcium concentrations induce S100A8/S100A9‐tetramers preventing TLR4‐binding and limiting their inflammatory activity. So far, only antimicrobial functions of released S100A8/S100A9‐tetramers (calprotectin) are described. It is demonstrated that extracellular S100A8/S100A9 tetramers significantly dampen monocyte dynamics as adhesion, migration, and traction force generation in vitro and immigration of monocytes in a cutaneous granuloma model and inflammatory activity in a model of irritant contact dermatitis in vivo. Interestingly, these effects are not mediated by the well‐known binding of S100A8/S100A9‐dimers to TLR‐4 but specifically mediated by S100A8/S100A9‐tetramer interaction with CD69. Thus, the quaternary structure of these S100‐proteins determines distinct and even antagonistic effects mediated by different receptors. As S100A8/S100A9 are released primarily as dimers and subsequently associate to tetramers in the high extracellular calcium milieu, the same molecules promote inflammation locally (S100‐dimer/TLR4) but simultaneously protect the wider environment from overwhelming inflammation (S100‐tetramer/CD69). Mechanisms restricting local inflammation and preventing systemic spreading of diseases are hardly understood. Release of S100A8/S100A9‐dimers at local sites of inflammation leads to monocyte activation via TLR4 while calcium‐induced S100A8/S100A9‐tetramer formation in the extracellular space mitigates monocyte dynamics via CD69. Thus, different quaternary structures of the same molecules promote inflammation locally (S100‐dimer/TLR4) but simultaneously protect systemic spreading of inflammation (S100‐tetramer/CD69).

PurposeIn the context of professional learning networks (PLNs), there are many studies which address knowledge mobilization (KMb). The majority of these focus on how research is mobilized by various actors. This paper explores the concepts of KMb both on an individual and an organizational level and discusses the role of PLN participants and PLNs as catalysts for institutional change (IC). To illustrate this, a model was developed which draws on a concept that depicts the mobilization processes at the various levels.Design/methodology/approachThe model was developed by drawing on theoretical approaches to both KMb on an individual and an organizational level of schools. The strengths and limitations of the model are then assessed as part of an exploratory study. Interviews of PLN participants (n = 7) from two schools and detailed logbooks of two participants were used to reconstruct experiences of KMb in the PLNs and the process of KMb among schools. By contrasting two schools, the study traces how mechanisms of KMb occurred. Data sources were analyzed using a structured content analysis alongside a deductive–inductive code system.FindingsThe results of the exploratory study show that, although the model is able to map the KMb practices, some refinement is still needed. While the extension of concepts describing the work of knowledge mobilizer (KM) leads to a more theoretically differentiated perspective, the data also showed that PLN participants only partially define themselves as KMs. The connection to concepts of strategies of knowledge mobilizing on an organizational level led to an increased transparency in the theoretical model. The data showed that KMb is influenced by organizational and individual beliefs.Originality/valueThe paper adds to the current knowledge base through a theoretical model that addresses the underinvestigated topic of KMb regarding the link between the individual and organizational levels. With a special focus on individual and organizational levels, a connection between KMb and IC is provided. The theoretical framework and research findings from an additional explorative study can be used to further develop relevant insights into the actions of participants from PLNs that enable IC processes among their schools.

This study defines the assemblage, materials, and mechanical parameter of the XIV century Bargello Palace at Florence (Italy). For this purpose, according to the rule in force, NDT and LDT had been performed on the Bargello walls, namely: direct observations, georadar, ultrasonic, thermic, DAC-test, and endoscopy. The results outline that the Bargello masonries are well done, as use in Florence in the XIV–XV centuries; they are solid walls, made in tightly sealed flat quoins, with external facing and internal plastering, and with a percentage of stones to mortar equal to about 70%. The results allow assigning of the Bargello’s masonry to one of the categories provided by the rules in force, with the relative mechanical parameter values for the need of a seismic verification assessment.

The conservation of a primary importance historical building requires organization, management, continuous updating, comparison, and visualization of a large amount of data of different nature and origin. In relation to these aspects the use of a GIS brings various advantages including single and univocal management of the entire amount of existing data in a relational, dynamic, updatable and queryable way. The integration of a mobile solution permits the updating of the dataset and checking on site all information. The workflow presented uses opensource solutions, desktop and mobile, which allows the creation of an unconventional lithological Field Mapping activity: starting from photo interpretation and in situ survey, all the coating materials (stone, etc.) of some monuments of primary historical and cultural interest have been mapped (i.e., Duomo di Firenze, Duomo di Prato). The product can be considered as a lithological cartography, vertically oriented, processed by field surveys, geognostic surveys and photo interpretation. All combined to create a “lithological” mapping of the coatings of the various monuments; the advantage is a new approach for conservation and restoration of Cultural Heritage. The proposed workflow involves a mobile solution, opensource, that allows the verification and management of the database in the field.

This study defines the assemblage, lithotypes and mechanical parameters of the building stones used for the external cladding of Prato’s Cathedral and Bell Tower (XIV century), now subject to extensive conservation work. By means of a drone flight, a full 3D model of the Cathedral and Bell-Tower complex was developed with photoplanes of the façades. On this basis, a GIS of the façades with all the stone elements embedded was developed. Historical data and organoleptic analysis enabled the identification of the types of the stones constituting the cladding. The results show that the building stones used for the cladding are all local historical stones, namely white Alberese and Palombini limestones, green Verde Prato peridotites, and grey Pietra Serena sandstone. The quarries of provenance of these stones were determined, along with their physical-mechanical properties and decay processes, in order to contribute to conservation works according to authenticity and integrity principles.