Understanding the relationship between surface and deep geological processes in tectonically active settings is crucial for unraveling the factors controlling landscape evolution and topographic growth. Here, we present the first basin-averaged 10Be-derived denudation rates for the Albanides, a subduction orogen in the Central Mediterranean. By integrating these data with topographic and fluvial analyses, we quantify Quaternary uplift rates and better constrain the spatial and temporal distribution of tectonic deformation, linking the existing long-term thermochronological data with short-term river incision rates. Denudation rates from nine basins range from 0.18 to 1.28 mm/yr, showing a general increase from the external compressional domain to the internal extensional domain. The denudation rates, calculated in catchments assumed to be in dynamic equilibrium and hence interpreted as proxies for uplift, reveal a consistent spatial pattern of tectonic uplift that aligns with active tectonic structures. Higher rates are observed in basins located at the hanging wall of thrust faults or at the footwall of normal faults. The imprint of active tectonics in the landscape is indicated by evidence of river network reorganisation and in the topography. A broad, across-strike increase in mean elevation, combined with local topographic variations along faults, suggests tectonic control on relief, modulated by lithological contrasts. We considered this uplift signal to be potentially controlled by a combination of both deep (e.g., crustal accretion) and shallow (i.e., surface faulting) processes. The former appears to drive the regional topographic pattern, while the latter contributes to localized uplift signals, enhanced denudation rates, and drainage reorganisation.

The development of robust catalysts that can work under harsh conditions bring promise but a challenge for photocatalytic hydrogen peroxide production. Here, we report the design of thiazole-based homologous heteropolyaromatic COFs (TTT-COF) via post-cyclization reaction for photocatalytic H2O2 production and aerobic oxidation of C(sp3)-H bonds. Our studies demonstrate that the elemental S heteroatom enables modified COF materials with high chemical stability, continuous π-conjugation, efficient electron and energy transfer, and an enhanced donor-acceptor (D-A) structure and charge separation, thus boosting their intrinsic photocatalytic activities and stability. Consequently, TTT-COF achieves a photosynthetic H2O2 production rate of 29.9 mmol g−1 h−1 with more than 200 hours of long-term stability when employing 10 % benzyl alcohol (V/V) as a sacrificial agent. Notably, the TTT-COF photocatalyst exhibits high reactivity in the oxidation of ethylbenzene derivatives. We believe this strategy offers a promising pathway to synthesize homologous heteropolyaromatic COFs and holds the potential for large-scale production of COF materials with tailored properties for broad applications in photocatalysis and beyond.

Achieving modular, selective and homogeneous protein modifications is of utmost importance for the design of next generation biopharmaceuticals, especially in the context of antibody-drug conjugates (ADCs). Here, we introduce unsaturated phosphine oxides as versatile triple-reactive reagents, allowing orthogonal chemoselective bioconjugation schemes. Starting from triethynyl-phosphine oxide, a variety of functionalized diethynyl-triazolyl-phosphine oxides (DTPOs) could be accessed by using CuI-catalyzed azide-alkyne cycloaddition (CuAAC). We showcase DTPO-reagents in the fast and selective generation of various highly stable antibody-conjugates via antibody disulfide rebridging. A highlight from this methodology is the synthesis of a DAR 4 ADC following a modular 2-step strategy using bioorthogonal tetrazine-labeling with bicyclo-[6.1.0]non-4-yne (BCN) or trans-cyclooctene (TCO) containing payloads. Notably, the DTPO-rebridged ADC exhibited potent cytotoxicity against Her2+ cancer cells. Moreover, we utilize triethynyl-phosphine oxide to obtain ethynyl-ditriazolyl-phosphine oxides (EDPOs) which enable a unique, single-reagent peptide-cyclization-bioconjugation protocol resulting in functional cyclic peptide-protein conjugates. Overall, our work provides versatile and powerful chemoselective modalities for the controlled modification of antibodies, peptide-cyclization and peptide-protein conjugation, expanding the toolkit for chemical biology and therapeutic development.

Organic molecular dimers serve as valuable model systems for manipulating and exploring interchromophore interactions. However, the structural flexibility introduced by linker or chromophore rotation gives rise to conformational isomers with distinct atomic arrangements, complicating the interpretation of photophysical processes. In this study, we investigate 9,9′,10,10′-tetraphenyl-2,2′-bianthracene (TPBA) to elucidate the distinct electronic characteristics of its two primary rotational isomers: syn- and anti-TPBA. To address the “Janus-type” photophysical behavior of these isomers, we employed a comprehensive suite of static and time-resolved spectroscopic techniques, including excitation-wavelength-dependent time-resolved photoluminescence, transient absorption, and time-resolved electron paramagnetic resonance, complemented by theoretical calculations. syn- and anti-TPBA exhibit markedly different emissive properties and charge-transfer characteristics, reflecting their unique exciton coupling behaviors. Additionally, they showcase distinct triplet formation rates and exhibit environment-dependent triplet formation mechanisms. This in-depth study of the Janus-like electronic properties of TPBA underscores the critical role of conformational isomerism in organic molecular dimers. Neglecting these structural variations can obscure the true photophysical landscape and lead to misinterpretations of mechanistic processes, highlighting the necessity of considering conformational heterogeneity in molecular design and photophysical studies.

Application of chemical compounds for the control and prevention of arthropod infestations is standard in small animal veterinary medicine. However, concerns about potential negative effects of such substances in the environment, including their circulation in water, soil or plants, and consequent impacts, including infertility or death of sensitive non-target organisms, such as bird, fish, and insects, in particular pollinators, are increasing. Factors that determine the risk of environmental harm from different chemicals are not only their release, but also their retention, bioavailability, degradation, accumulation in different environmental compartments, bioaccumulation in different organisms or their organs, and the effects of excipients commonly used in drug formulations vs. not medical or veterinary use of chemicals. Here we briefly review the substance classes of insecticides, acaricides, or repellents used in veterinary medicine, their effects and possible side effects, and their fate in the environment, including reports of undesirable environmental impacts. In addition to existing literature, the possibilities of preventing, reducing and containing the unwanted release of such chemicals from animal treatments and the pivotal role of experts in veterinary parasitology are discussed. Knowledge gaps concerning the properties of chemicals used for the control of ectoparasites in veterinary medicine that must be addressed in future research are emphasized.

Background

Childhood maltreatment increases the risk for mental disorders, including postpartum depression (PPD). Outside the peripartum period, attenuated long-term hypothalamic-pituitary-adrenal (HPA) axis regulation and perceived chronic stress are discussed as potential mechanisms underlying the adverse effects of childhood maltreatment. Hair cortisol concentration (HCC) enables the detection of long-term changes in HPA axis regulation. This study aimed to examine the mediating role of HCC in linking childhood maltreatment with symptoms of PPD.

Methods

We measured childhood maltreatment, symptoms of PPD and chronic stress via online questionnaires in N = 111 individuals 12 months after childbirth. Current and past major depressive episodes were assessed using the Structured Clinical Interview for DSM-5. To determine HCC from months 09–12 postpartum, participants provided self-collected hair samples. Mediated regression models examined the role of HCC and chronic stress for the relation between childhood maltreatment and PPD symptoms.

Results

Childhood maltreatment predicted higher levels of PPD symptoms and chronic stress, and was associated with higher rates of a current depressive episode, but not with HCC. Perceived chronic stress mediated the relationship between childhood maltreatment and symptoms of PPD.

Interpretation

Individuals with a history of childhood maltreatment are highly vulnerable to adverse mental health outcomes in the postpartum period. Perceived chronic stress may be an important underlying pathway, while neuroendocrinological mechanisms linking CM and PPD remain poorly understood. Longitudinal studies are needed to improve our understanding of the pathways between CM and PPD, thereby enabling the development of targeted prevention and intervention strategies.

A mechanistic understanding of how intracellular pathogens evade the intrinsic defenses of their host cells could open up intriguing therapeutic opportunities. Here, we applied a genome-wide genetic screening approach to investigate the nature of the defensive host cell death response suppressed by the membrane trafficking modulator CpoS, an effector protein secreted by the obligate intracellular bacterial pathogen Chlamydia trachomatis. Initially, this work revealed a CpoS-deficient mutant to exhibit a markedly increased dependence on host cellular synthesis of ceramides, the precursors of complex sphingolipids. Using novel microscopic reporters, we then established CpoS’ role in defense evasion to occur by preserving the integrity of Chlamydia’s parasitophorous vacuole (the inclusion) via ensuring an adequate sphingolipid supply. More specifically, we observed CpoS deficiency to destabilize inclusions, initially characterized by a release of individual bacteria into the host cell cytosol, then followed by inclusion rupture concomitant with host cell death. Exogenous addition of sphingosine stabilized CpoS-deficient inclusions, whereas disruption of host cellular ceramide synthesis destabilized wild-type inclusions. In combination, CpoS deficiency and impaired ceramide synthesis – presumably disrupting both Chlamydia’s vesicular and non-vesicular sphingolipid supply routes – destabilized inclusions even earlier, resulting in infection clearance and host cell survival rather than host cell death. Overall, this study highlights how the vacuolar pathogen C. trachomatis maintains vacuole integrity by ensuring a steady sphingolipid supply, potentially offering inspiration and directions for future therapeutic strategies targeting parasitophorous vacuoles.

High prevalences of mental disorders have been found among people from Arabic-speaking countries. Perceived social support has often been identified as a significant factor in the development of mental disorders, and the social environment is especially important with respect to treatment-seeking. However, the extent to which different sources of perceived social support are associated with mental health remains unclear. This cross-sectional study examined latent profiles based on perceived social support from different sources, and examined their relationship with sociodemographic characteristics, psychopathological symptom severity, and quality of life (QoL). The sample consisted of N = 5,977 treatment-seeking adults from different Arabic-speaking countries. Latent profile analysis was performed to identify subgroups of individuals based on perceived social support from family, friends, and significant others. Multinomial logistic regression was used to analyze predictors of profile membership. Differences between profiles regarding depressive, posttraumatic stress, somatoform symptom severity, and QoL, were examined using tests for equality of means. We identified a five-profile class-invariant unrestricted solution. Marital status, sex, age, education, and country of origin were significant predictors of profile membership. The profiles differed significantly regarding depressive, posttraumatic stress, and somatoform symptom severity, and QoL. Participants perceiving moderate to high social support from different sources indicated lower psychopathological symptom levels. The low perceived social support profile showed lower QoL compared to all other profiles (p < .05). Individuals who perceive low social support from different sources appear to show higher psychopathological symptom severity and lower QoL. Our key finding reveals that individuals with multi-source support profiles showed significantly lower psychopathological symptom severity and higher quality of life compared to those with limited support profiles. Social support perception varies systematically between participants from different Arabic-speaking countries, with individuals from more stable countries reporting higher perceived support. Therefore, clinical interventions should integrate family members and community networks as integral components to enhance therapeutic outcomes. At a systemic level, policy initiatives should focus on strengthening societal-level support infrastructure, with approaches tailored to the local political and economic contexts of the target populations. Enhancing perceived social support must be prioritized not only within psychotherapy but also through diverse societal levels, to promote sustained mental health in Arabic-speaking countries

Despite the complexity of real-world environments, natural vision is seamlessly efficient. To explain this efficiency, researchers often use predictive processing frameworks, in which perceptual efficiency is determined by the match between the visual input and internal models of what the world should look like. In scene vision, predictions derived from our internal models of a scene should play a particularly important role, given the highly reliable statistical structure of our environment. Despite their importance for scene perception, we still do not fully understand what is contained in our internal models of the environment. Here, we highlight that the current literature disproportionately focuses on an experimental approach that tries to infer the contents of internal models from arbitrary, experimenter-driven manipulations in stimulus characteristics. To make progress, additional participant-driven approaches are needed, focusing on participants’ descriptions of what constitutes a typical scene. We discuss how recent studies on memory and perception used methods like line drawings to characterize internal representations in unconstrained ways and on the level of individual participants. These emerging methods show that it is now time to also study natural scene perception from a different angle—starting with a characterization of an individual’s expectations about the world.

Functional traits provide key insights into ecological strategies and evolutionary diversification. In this study, we analyzed a comprehensive trait dataset to investigate morphological predictors of feeding ecology in testate amoebae from the Northern Holarctic realm, focusing on variability across 372 species. We also examined whether trait diversity mirrors taxonomic richness at the family level. Morphological traits included shell length, shell width, aperture dimensions, shape, and covering. The Principal Component Analysis (PCA) indicated that Axis 1 predominantly represented variation in shell and aperture size, while Axis 2 was associated with differences in overall shape proportions. Bacterivorous species exhibited the greatest morphological and taxonomic diversity, spanning 21 families and 48 genera, with mixotrophs and predators occupying nested subsets of their broader morphospace. The regression analyses demonstrated significant associations between species richness and variation in protective features, including aperture rim morphology and the presence of spines. Decision tree models identified the aperture width-to-length ratio as a key predictor of feeding strategy, although classification accuracy was lower for mixotrophs and predators. Future research should integrate shell morphology with phylogenetic data to enhance ecological strategy predictions in testate amoebae and explore hypotheses regarding functional diversification across a broader geographical scale and within different environments.

Streptococcus suis is an important zoonotic pathogen that can cause severe infections in both humans and pigs. The prevalence of S. suis serotype 14 in sporadic cases in China has been gradually increasing during recent years. However, the current understanding of S. suis serotype 14 is limited. In this study, we investigated the population structure, phylogenetic relationships, antimicrobial resistance, and pathogenicity of 125 S. suis serotype 14 strains. These strains clustered into 12 sequence types (STs) and three clonal complexes (CCs), with ST7 accounting for the highest proportion (73.6%), which indicates significant pathogenic potential, given that ST1 and ST7 are well-known high-virulence STs in S. suis. Bioinformatic analysis showed that all serotype 14 strains carry the virulence genes sly and epf, while 74.4% of the strains carry the virulence gene mrp. In the pathogenicity test (n = 5), the human strain Ss2301, Ss2401, and the porcine strain L966, SC42 proved to be highly virulent strains. These data highlight the virulence potential of serotype 14 S. suis. Tetracycline resistance genes and macrolide, lincosamide, and streptogramin B (MLSB) resistance genes were most frequently detected in the population. The transmission of the former genes mainly depends on integrative and conjugative elements (ICEs), while the latter depends on both ICEs and prophages. This study not only confirmed the pathogenic potential of serotype 14 S. suis but also provided valuable information for improving prevention and control strategies for S. suis infections.

Streptococcus canis is an important opportunistic pathogen of cats, dogs, and cows, which can cause a range of infections, ranging from skin and soft tissue infections to septicemia and endocarditis. As a zoonotic agent, S. canis has also recently been implicated in serious human infections, following trauma or immunosuppression. In this work, we describe a novel protease of S. canis, termed IdeC (Immunoglobulin G degrading enzyme of S. canis), which may be involved in bacterial immune evasion. The cleaving ability of IdeC against IgG from various species was assessed; this revealed that IdeC successfully cleaved canine, feline, and human IgG. We also confirmed that IdeC is a cysteine protease, similar to IdeS of Streptococcus pyogenes. Investigation of the cleavage site in IgG sequences showed that it is highly conserved across IgGs from all species tested. From this analysis, it was determined that IdeC cleavage occurs between the CH2 and hinge regions of IgG. Interestingly, feline IgG was consistently cleaved with the highest efficiency, with human and canine IgG displaying less efficient cleavage. High-resolution crystal structures of two IdeC constructs provided insights into the catalytic machinery and substrate recognition. Modeling of the full-length IdeC:IgG complexes for human, canine, and feline cases explains the mechanism of action of the protease and reveals the molecular basis for the observed cleavage preference for feline IgG. Understanding and managing S. canis as a pathogen is important in both veterinary and human medicine, as this bacterium underscores the need for awareness of zoonotic transmission.

There is a dire lack of standardized in vivo studies investigating the human hazard by microplastics by OECD test guidelines. The lack of suitable test materials contributes to this situation. Here we report on results of test guideline 407 with 28-day oral exposure of male rats to small microplastic (polyamide (PA-6) with a size distribution from 2.2 µm to 16.5 µm). The tested material was chosen by the boundary conditions that a relatively large amount (0.3 kg) should be available with size as small as possible, with realistic shapes (irregular, not spherical) and with composition as representative as possible for pristine PA-6. The conditions were met by extracting the smallest 0.1% of particles from the “fines” that are rejected during commercial production of 3D printing powder, whereof tons are produced as intermediate for selective laser sintering. This strategy of generating larger amounts of microplastic test materials may be accessible also for other types of plastic. The study was performed as limit test in accordance with OECD test guideline 407 applying 1000 mg test substance/kg body weight/day for 28 days. Hematological and clinical chemical examinations were performed at the end of the administration period. All organs listed in the guideline were assessed, including histopathology. Under the current study conditions, no local or systemic toxicological effects were seen after 28-day oral exposure to PA-6.

One key barrier to applying deep learning (DL) to omics and other biological datasets is data scarcity, particularly when each gene or protein is represented by a single sequence. This fundamental challenge is mainly relevant in research involving genetically constrained organisms, organelles, specialized cell types, and biological cycles and pathways. This study introduces a novel data augmentation strategy designed to facilitate the application of DL models to omics datasets. This approach generated a high number of overlapping subsequences with controlled overlaps and shared nucleotide features through a sliding window technique. A hybrid model of Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) layers was applied across augmented datasets comprising genes and proteins from eight microalgae and higher plant chloroplasts. The data augmentation strategy enabled employing DL methods on these datasets and significantly improved the model performance by avoiding common issues such as overfitting and non-representative sequence variations. The current augmentation process is highly adaptable, providing flexibility across different types of biological data repositories. Furthermore, a complementary k-mer-based data augmentation strategy was introduced for unlabeled datasets, enhancing unsupervised analysis. Overall, these innovative strategies provide robust solutions for optimizing model training potential in the study of datasets with limited data availability.

The photolysis of 1-phosphabarrelenes, generated from 3,5-diarylphosphinines and benzyne in a [4 + 2] cycloaddition reaction, affords hitherto unknown 2-phosphasemibullvalenes via di-π-methane rearrangement reaction. These compounds occur only as intermediates, while subsequent and rapid dimerization to 6-membered, cyclic diphosphanes with a P–P bond was observed. The results are in stark contrast to the photochemical conversion of 1-phosphabarrelenes, obtained from 2,4,6-triarylphosphinines and a strong dienophile. In this case, the corresponding 5-phosphasemibullvalenes are formed selectively and exclusively. Our results nicely demonstrate the strong impact of the substitution pattern of the starting material on the outcome of the di-π-methane rearrangement reaction.

Background Increasing prevalence of morbid obesity accompanied by comorbidities like type 2 diabetes mellitus (T2DM) led to a demand for improving therapeutic strategies and pharmacological intervention options. Apart from genetics, inflammation processes have been hypothesized to be of importance for the development of obesity and related aspects like insulin resistance.Main textWithin this review, we provide an overview of the intricate interplay between chronic inflammation of the adipose tissue and the hypothalamus and the development of obesity. Further understanding of this relationship might improve the understanding of the underlying mechanism and may be of relevance for the establishment of new treatment strategies.

Background Urinary tract infections (UTI) in men differ relevantly to women by their pathogens. Gram-positive uropathogens play a relevant role in UTI in men. In this study, we aimed to analyze the epidemiology of Enterococcus faecalis in UTI in male outpatients.Methods We conducted a retrospective observational multicenter study during 2015 to 2020 consisting of urine samples of 99,415 adult male outpatients sent from 6,749 outpatient practices from Germany. Proportions were compared using the z-Test and 95% confidence intervals were calculated using the Clopper-Pearson method.Results E. faecalis is the 2(nd) most frequent bacteria (16%) detected in suspected UTI in male outpatients. Young men are predominantly at risk (17%) for isolation of E. faecalis in suspected UTI. In polymicrobial infections E. faecalis is isolated in 47% of all suspected UTI in men. Recurrency of suspected UTI is significantly more frequent when E. faecalis is isolated compared to Escherichia coli (22% vs 26%; p < .001). Recurrency rates of E. faecalis associated UTI increases by age from 12% (18-29 years) to 28% (>= 70 years); p < .001. Congruently the resistance of E. faecalis against ciprofloxacin increases by age from 22% (18-29 years; 2019) to 37% (>= 70 years; 2019); p < .001.Conclusions E. faecalis is frequently isolated in suspected UTI in male patients. Consequently, Nitrate-sticks results cannot be recommended to exclude UTI in men. The empirical use of ciprofloxacin in young adults can be reasonable. Frequent recurrences in E. faecalis associated suspected UTI emphasizes the importance of microbiological pathogen identification and susceptibility testing in men suffering from UTI.

Background The availability and correct use of personal protective equipment (PPE) to prevent and control infections plays a critical role in the safety of medical students in clinical placements. This study explored their experiences and perspectives in their final clerkship year with PPE during the COVID-19 pandemic.MethodsThis qualitative study was based on social constructivism and was conducted in 2021 at the Charite - Universitatsmedizin Berlin. In three online focus group discussions, 15 medical students in their final clerkship year reported their experiences with PPE training and use during the COVID-19 pandemic. Data were recorded, transcribed and analysed based on Kuckartz's approach to content analysis. We drew upon the a priori dimensions of the capability, opportunity, motivation - behaviour (COM-B) model as main categories as well as emergent issues raised by the study participants (subcategories).ResultsIn addition to the three main categories of the COM-B model, eleven subcategories were identified through inductive analysis. The study participants reported several factors that hindered the correct use of PPE. In the area of capabilities, these factors were related to learning experience with PPE in terms of both theoretical and practical learning together with later supervision in practice. In the area of opportunities, these factors included the limited availability of some PPE components, a lack of time for PPE instruction and supervision and inappropriate role modelling due to the inconsistent use of PPE by physicians and nursing staff. The area of motivation to use PPE was characterized by an ambivalent fear of infection by the SARS-CoV-2 virus and the prioritization of patient safety, i.e., the need to prevent the transmission of the virus to patients.ConclusionsOur study revealed several limitations pertaining to the enabling factors associated with the trainable behaviour "correct use of PPE". The concept of shared responsibility for student safety was used to derive recommendations for future improvement specifically for the medical school as an organization, the teachers and supervisors, and students themselves. This study may guide and stimulate other medical schools and faculties to explore and analyse components of student safety in clinical settings in times of infectious pandemics.

Background GHB (gammahydroxybutyrate) and its precursors are popular recreational drugs due to their sedative, anxiolytic and sexually stimulating effects. Their use has been steadily increasing in recent years. The detoxification process is complex and prone to high rates of complications while little is known about the pathophysiology. This study aims to elucidate the characteristics of GHB-addicted patients and to evaluate the risks and complications of GHB withdrawal treatment.MethodsThis observational study describes prospectively the socioeconomic status, clinical history and course of inpatient detoxification treatment of a group of 39 patients suffering from GHB substance use disorder. Detoxification treatment took place in a highly specialized psychiatric inpatient unit for substance use disorders.ResultsGHB patients were characterised by being young, well-educated and by living alone. More than 50% of the patients had no regular income. The patients were male and female in equal numbers. Detoxification treatment was complicated, with high rates of delirium (30.8%) and high need for intensive care (20.5%).ConclusionsIn our sample, GHB users were young, well-educated people and male and female in equal number. Detoxification proved to be dangerous for GHB-addicted patients. The presence of delirium and the need for transfer to an intensive care unit during detoxification treatment was extraordinarily high, even with appropriate clinical treatment. The reasons for this remain unknown. Therefore an intensive care unit should be available for GHB detoxification treatment. Further studies are needed to evaluate the options for prophylactic treatment of delirium during detoxification.

In three recent articles published in Nature and Cell, Weatherbee et al.1, Pedroza et al.2 and Liu et al.3 have demonstrated how human pluripotent stem cells can be coaxed to self-organize into compartmentalized structures that mirror post-implantation embryos. Building on the successful establishment of stem cell-derived mouse embryo models ex utero, these models now shed light on human embryo development during the period between implantation and gastrulation, which has so far been challenging to investigate.