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Organic amendments as a tool to restore soil microbial diversity after wildfires in native Mediterranean forests
No full textWildfires are intensifying under climate change and increasingly compromising the resilience of Mediterranean ecosystems. Soil restoration through organic amendments has been proposed as an effective tool to mitigate soil degradation after fires, yet there is limited knowledge on how different typologies of organic amendments influence soil microbial communities and the recovery of microbial-mediated functions. This study evaluated contrasting organic amendments—straw mulch, compost, and fresh swine and poultry manures—on soil microbial diversity and enzymatic activity in burned native sclerophyllous, Mediterranean forest in central Chile, the earliest in its type experiencing effects of climate change. The study took place six months after amendment application and two years after a wildfire occurrence. Enzyme activities showed different responses according to organic amendments type: while manures strongly stimulate enzymes (urease, glucosidase, and phosphatase activities), compost and mulch promoted a gradual effect on nutrient cycling. Fungal biomass, reduced by fire, recovered best under compost and swine manure. However, organic amendments significantly reduced eukaryotic alpha diversity and differentiated communities from unburned soils and burned soils with no amendment. In contrast, only manures reduced alpha diversity in prokaryotes, while beta diversity analyses revealed that compost amended soils maintained communities closer to reference conditions. Overall, manures provided short-term functional improvements in burned soils, but compost supported a more balanced recovery, preserving microbial communities closer to unburned soils. Therefore, the compost amendment can represent a practical and ecologically safer strategy to accelerate post-fire soil restoration. Targeted application, for example through “fertile islands” in the most degraded areas, may enhance soil resilience while minimizing ecological risks in fire-sensitive landscapes.</p
Urban environment in early-life and brain morphology in preadolescents
No full textRapid urbanization leads to increased exposure to air pollution, limited greenness, and denser built environments. However, evidence on how these urban factors influence brain development remains limited. We investigated associations between urban characteristics during pregnancy and childhood and brain morphology in preadolescence. The study included 2895 children from the Dutch Generation R Study, with replication in 92 children from the French PELAGIE cohort. Twelve built environment and four urban natural space indicators were estimated at residential addresses during pregnancy and childhood. Brain outcomes included cortical gray matter, cerebral white matter, cerebellum, corpus callosum, subcortical structures volumes, cortical thickness, and surface area assessed at 9–12 years. We applied multi-exposure regression models with data-driven variable selection and assessed mediation by air pollution and road-traffic noise, adjusting for confounders. In Generation R, higher NDVI during pregnancy was associated with smaller cortical gray matter volume (-5132 mm3; 95 % CI: -8611, -1652), and higher facility richness with larger nucleus accumbens volume. During childhood, higher distance to blue space was associated with larger cortical gray matter volume, and higher transport land use with smaller hippocampus. No mediation by air pollution or road-traffic noise was observed. In PELAGIE, associations were consistent but not statistically significant. Cortical thickness was associated with several built environment indicators during childhood, and surrounding greenness was linked to smaller surface area in specific cortical regions. Our findings suggest that early-life exposure to urban environments may influence brain morphology, with distinct contributions from green space, blue space, and built environment factors.</p
Intra- and inter-observer reliability of ultrasound muscle thickness of gluteal and biceps femoris long head in individuals with and without SCI
No full textPURPOSE: This study aimed to evaluate both inter- and intra-observer reliability of ultrasound-based muscle thickness measurements in able-bodied (AB) individuals, as well as intra-observer reliability in individuals with spinal cord injury (SCI).METHODS: Ultrasound measurements of the gluteus maximus, medius, minimus and biceps femoris long head were performed on 31 AB participants and 30 participants with SCI. Each AB participant was scanned on two occasions by three observers, with three repetitions per muscle per occasion. The muscle thickness in participants with SCI was measured using three repetitions during a single test occasion, conducted by one observer. A generalizability (G) study was conducted to assess the reliability of the measurements.RESULTS: In AB participants, intra-observer reliability for gluteal muscles ranged from G-coefficient: 0.57 to 0.89, and for biceps femoris long head from G-coefficient: 0.60 to 0.76. Inter-observer reliability in AB participants was G-coefficient:0.48-0.72 for the gluteal muscles and G-coefficient: 0.52 for the biceps femoris. In contrast, intra-observer reliability in participants with SCI was excellent across all muscles (G-coefficient: 0.95-0.99).CONCLUSION: Ultrasound can assess muscle thickness with moderate to good intra-observer reliability in AB participants, but with only poor to moderate inter-observer reliability. In contrast, intra-observer reliability was excellent in participants with SCI. Reliability depends on observer experience and varies across muscles and populations.</p
Navigating 3D Chemical Space:The Design, Synthesis and Exploration of 3D Fragment Libraries
No full textIn the late 1990s, fragment-based drug discovery (FBDD) emerged as a novel method for hit identification, complementing existing strategies such as high-throughput screening (HTS). Rather than screening drug-sized molecules, FBDD focuses on smaller fragment-sized compounds with molecular weights of up to 300 Da. Owing to their reduced complexity, fragments sample chemical space efficiently, which allows for the use of significantly smaller libraries that typically comprise only a few thousand compounds. Historically, fragment libraries have been dominated by relatively flat, (hetero)aromatic scaffolds. Although such libraries have successfully yielded several clinically approved drugs and numerous clinical candidates, 2D fragments explore only a narrow region of chemical space and may bias discovery toward planar chemotypes with suboptimal three-dimensional fit. In contrast, 3D fragments offer greater diversity in terms of shape and exit vectors, which, depending on the target, may better complement the three-dimensional nature of protein binding sites. This has led to growing interest in incorporating 3D fragments alongside traditional 2D libraries. However, 3D fragments also present challenges, including reduced synthetic accessibility and potentially lower hit rates. This thesis explores the challenges, as well as the opportunities, associated with 3D fragments across the key stages of fragment-based drug discovery. Following an introduction in Chapter 1, the thesis commences in Chapter 2 with a comparative analysis of the metrics commonly used to quantify the three-dimensional character of fragments, including the fraction of sp3-hybridized carbons (Fsp3), Plane of Best Fit (PBF), and Principal Moments of Inertia (PMI). Implications for their use in (fragment) library design are discussed. Chapter 3 describes the development of an automated, open-source workflow for fragment library design. The workflow is highly customizable and accounts for chemical diversity and novelty, but also allows for the incorporation of the 3D metrics evaluated in Chapter 2. To demonstrate its utility, we used it to design and synthesize a focused set of cyclopropane-based 3D fragments as isolated cis- and trans-isomers. Chapter 4 details the synthesis of two focused libraries containing a total of 28 spirocyclic cyclobutane fragments, designed using the automated workflow described in Chapter 3. It describes the large-scale synthesis of diastereomerically pure building blocks and their parallel chemistry-based derivatization into the two focused libraries, each composed of isolated sets of achiral diastereomers. Chapter 5 describes the identification of a cyclobutane-based 3D fragment hit targeting the Histamine H1 receptor (H1R), discovered by screening a diverse 80-membered set of 3D fragments comprising various aliphatic (hetero)cyclic scaffolds. Following several rounds of SAR-driven optimization, the high-affinity antagonist VUF26691 (pKi = 8.8) was identified, with retention of the cyclobutane core throughout the optimization. Chapter 6 describes the development of the Exit Vector Fingerprint (EFVP) as a novel method for designing 3D fragment libraries. Rather than relying on overall molecular shape or atom hybridization, it employs exit vector geometry, combined with the pharmacophoric features residing on those vectors, as a more pharmacologically relevant basis for describing three-dimensionality. In addition to providing a practical tool for designing the next generation of 3D fragment libraries, the EVFP offers a refined conceptual framework for evaluating three-dimensional fragments. Finally, Chapter 7 provides an integrated discussion of the findings presented throughout the thesis and outlines future perspectives
Insights into the translation and adaptation of an instrument for measuring time processing abilities among individuals with visual and intellectual disabilities
No full textBackground: People with visual and intellectual disabilities frequently face challenges in daily time management. However, there is no validated instrument for assessing underlying time-processing abilities in Dutch-speaking individuals, in general nor for this specific target group. Aims: This study aimed to translate and adapt the KaTid®-Adult instrument, originally developed in Sweden, for application in this population in Belgium (Flanders) and the Netherlands. In addition, the goal was to make the instrument more accessible to people with visual impairments. Method: The researchers translated and adapted the KaTid®-Adult, following World Health Organization guidelines and conducted pilot tests. Results: This descriptive study explains expected and unexpected issues encountered during the translation and adaptation. Conclusions: The outcome is that the KaTid®-Adult-NL is a culturally relevant instrument for measuring time processing abilities in individuals with visual and intellectual disabilities in Belgium (Flanders) and the Netherlands. However, the KaTid®-Adult was not initially designed for people with a visual impairment. In this study, first steps were taken to make the instrument accessible to people with visual impairments.</p
Basic dimensions of leader personality:a lexical study in Hebrew
No full textTraditional trait-based leadership research relies on generic personality models, overlooking the context-specific nature of personality. We used the lexical approach to develop a leadership-focused personality taxonomy. We identified 199 adjectives for describing leaders (Study 1) and factor analyzed leaders’ (Study 2, N = 402) and followers’ (Study 3, N = 421) ratings of these adjectives. Analyses revealed five dimensions shared across groups, closely related to, yet distinct from the Big Five and HEXACO factors: Energy, Psychopathy, Organization, Irritability, and Intellect. Two follower-specific dimensions—Supportiveness and Weakness—also emerged. Relationships with the Big Five, HEXACO, and leadership criteria supported construct and concurrent validity. Study 4 replicated the structure in samples of military (N = 226) and religious (N = 202) leaders.</p
Deciphering the molecular pharmacology of the histamine H3 receptor
No full textThe histamine H3 receptor (H3R) is a G protein-coupled receptor predominantly expressed in the central nervous system, where it regulates the release of histamine and other neurotransmitters involved in cognition, arousal, and sleep-wake regulation. Although H3R has been validated as a therapeutic target, the limited clinical success of H3R-directed drugs highlights the need for improved pharmacological tools and a deeper understanding of H3R signaling complexity. This thesis investigates H3R pharmacology through the development of novel photopharmacological tools, analysis of ligand-biased signaling, and characterization of seven alternatively spliced H3R isoforms. Photopharmacological strategies were applied to create a light-activated H3R agonist, enabling spatiotemporal control of receptor activation. Pharmacological profiling of human H3R isoforms revealed differences in ligand binding affinities depending on their level of constitutive activity. In addition, several synthetic agonists and receptor isoforms preferentially recruit mini-Gi protein while minimally engaging β-arrestin1 or β-arrestin2, as revealed by receptor-proximal biosensor assays. Together, these findings demonstrate that H3R signalling is shaped by ligand properties, optical control, and receptor isoforms, providing new tools and insights that may support the development of pathway-selective and isoform-aware strategies for targeting the H3R
Dual-mode mid-infrared plasmonic metasurface for real-time label-free analysis of live cells
No full textReal-time, label-free monitoring of living cells is a central goal in biosensing, and mid-infrared spectroscopy is uniquely suited to this task because it directly probes the vibrational fingerprints of biomolecules within cells. However, its use in live-cell analysis is limited by weak absorption signals and strong water background. Here, we introduce a double-resonant plasmonic metasurface composed of gold rod-shaped nanoantennas specifically engineered to overcome these limitations. This metasurface provides two complementary spectral readouts: (i) a strong plasmonic resonance matched to the amide I–II vibrational bands of proteins, and (ii) a sharp reflectance dip around 1900 cm−1 optimized for refractive-index mass sensing via plasmonic redshift. Initial validation with red blood cell sedimentation showed sensitivity to time-dependent refractive index variations corresponding to ∼3.5 ng of deposited material. We then applied this technology to a clinically relevant model, monitoring SAS oral squamous carcinoma cells treated with 18β-glycyrrhetinic acid, a natural compound with pro-apoptotic effects. Treatment resulted in a clear decrease in both the plasmonic redshift signal and the integrated amide absorption, consistent with biophysical and biochemical alterations associated with apoptosis. Spectral deconvolution of the amide I region revealed specific shifts in protein secondary structures, including a decrease in α-helical content, further supporting apoptosis-related molecular changes. These findings show that our plasmonic metasurface can sensitively monitor real-time cellular responses, supporting applications in drug screening, spectral biomarker discovery, and opening new opportunities in cell-based diagnostics and biosensing.</p
Prophecy and Power:Predictive Texts and Politics in the Hellenistic Near East
No full textThe Hellenistic period was a turbulent era, in which great changes occurred in the fields of culture and religion. Developments took place in the literature that was written in this period as well. In the centuries after the death of Alexander the Great, texts were composed throughout the Near East which combine a description of political events with a prediction of the future. Such texts often display a strong interest in kingship and in events such as battles, revolts and dynastic struggles. Strikingly, they conclude with a prediction about the arrival of an ideal ruler, who will instigate a golden age. Were such texts composed for a specific purpose, such as criticizing Greek rule? Was the emphasis on political events a literary development, instigated by the changing world of the Hellenistic period? This thesis discusses three predictive texts from the Hellenistic period: the visions of Daniel (chapters 7 to 12) from Judaea, the Dynastic Prophecy from Babylonia and the Potter’s Oracle from Egypt. The texts are translated, analysed and compared in order to shed light on the historical context, social background and political function of predictive literature in the Hellenistic Near East
