julilili42/papers huggingface dataset:
Unveiling social relationships: exploring the importance of relationships as a moderator of the link between effort-reward imbalance and leader-member exchange among healthcare professionals
2024-08-10

Abstract Objective Healthcare professionals are at increased risk of experiencing occupational stress and its detrimental stress-sequalae. Relevant theories that contribute to the subjective experience of occupational stress have been identified, such as the model of effort-reward imbalance (ERI) and the concept of leader-member exchange (LMX). The aim of this study was to examine how the perceived importance of social relationships at work moderates the relationship between LMX and imbalance ERI. Methods A survey was conducted among N = 1,137 healthcare professionals from diverse occupational categories in a tertiary hospital in Germany. ERI was gauged using the German version of the Effort-Reward Imbalance Questionnaire (ERI-S 10). The quality of leader-employee dyadic relationships was assessed using the German version of the Leader-Member Exchange (LMX-7). The importance of social relationships was assessed on the basis of a previously validated polarity profile. Results More than 75% of healthcare professionals reported high levels of ERI, with those involved in direct patient care particularly affected. On average, leaders rated relationship quality higher than their respective followers. Subjectively higher LMX was associated with lower ERI. This association was moderated by the perceived importance of social relationships at work. Higher subjective ratings of their importance led to a stronger association. Conclusion The study highlights the particular challenges faced in the healthcare sector. The results emphasize that the perceived importance of social relationships at work can play a key role in healthcare professionals’ job stress and underline the need for stress prevention programs that engage both leaders and followers.
The microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides
2024-08-12

ABSTRACT Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens in vitro and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of Staphylococcus aureus . Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of S. aureus within minutes due to protonophore activity. Varying the salt species and concentrations in buffers revealed that not only protons are transported, and we demonstrate the binding of the monovalent cations K + , Na + , and Li + to lugdunin. By comparing known ionophores with various ion transport mechanisms, we conclude that the ion selectivity of lugdunin largely resembles that of 15-mer linear peptide gramicidin A. Direct interference with the main bacterial metabolic pathways including DNA, RNA, protein, and cell wall biosyntheses can be excluded. The previously observed synergism of lugdunin with dermcidin-derived peptides such as DCD-1 in killing S. aureus is mechanistically based on potentiated membrane depolarization. We also found that lugdunin was active against certain eukaryotic cells, however strongly depending on the cell line and growth conditions. While adherent lung epithelial cell lines were almost unaffected, more sensitive cells showed dissipation of the mitochondrial membrane potential. Lugdunin seems specifically adapted to its natural environment in the respiratory tract. The ionophore mechanism is refractory to resistance development and benefits from synergy with host-derived antimicrobial peptides. IMPORTANCE The vast majority of antimicrobial peptides produced by members of the microbiome target the bacterial cell envelope by many different mechanisms. These compounds and their producers have evolved side-by-side with their host and were constantly challenged by the host’s immune system. These molecules are optimized to be well tolerated at their physiological site of production, and their modes of action have proven efficient in vivo . Imbalancing the cellular ion homeostasis is a prominent mechanism among antibacterial natural products. For instance, over 120 naturally occurring polyether ionophores are known to date, and antimicrobial peptides with ionophore activity have also been detected in microbiomes. In this study, we elucidated the mechanism underlying the membrane potential-dissipating activity of the thiazolidine‐containing cycloheptapeptide lugdunin, the first member of the fibupeptides discovered in a commensal bacterium from the human nose, which is a promising future probiotic candidate that is not prone to resistance development.
Computational Studies of Dimerization of [n]-Cyclacenes
2024-08-12

Cyclacenes, C<sub>4<i>n</i></sub>H<sub>2<i>n</i></sub>, consist of <i>n</i> linearly fused benzene rings that are arranged to result in a closed nanohoop structure. Cyclacenes are thus the cyclic versions of acenes and have so far escaped synthesis. In order to estimate the tendency of [<i>n</i>]-cyclacenes (6 ≤ <i>n</i> ≤ 20) to undergo dimerization, which is assumed to be a major pathway of degradation under oxygen-free conditions, we here report the energy of dimerization as computed by density functional theory using spin-restricted, spin-unrestricted, and thermally assisted-occupation (TAO) formalisms. It is found that the energy of dimerization increases with increasing size of <i>n</i> but that this increase is not monotonic for the smaller members of the series. This is due to the combination of the cryptoannulenic effect and the inherent strain of the cyclacenes. The energy of dimerization of the largest member inspected, [20]-cyclacene, is -59.3 kcal/mol, while we expect it to converge to -46 kcal/mol for <i>n</i> → ∞ based on comparison with data obtained for acenes.
Bringing Researchers and Practitioners Together: On the Aims of a Research Network in Organic Chemistry Education
2024-08-12

Given current social and ecological challenges such as climate change, energy supply, and e-mobility, the training of future generations of chemists will play a key role in preparing them for future demands and enabling them to develop innovative solutions for current and future problems. However, given the persistent perception of chemistry courses as challenging, the largely consistent high dropout rates in these courses, and the increasing demand for well-trained chemistry graduates, it seems necessary to pursue more coordinated research efforts to support students' chemistry learning at the university level and to increase the professionalization of instructors to improve the quality of teaching. In this communication, we outline the aims of a research network funded by the German Research Foundation and the growing need for increased collaborative research activities in higher education in the field of academic chemistry training as a blueprint for others in the community. We outline our objectives along four topics to address structured and systematic research efforts in organic chemistry education and teaching at the university level. A focus is placed on organic chemistry, as this discipline can provide a clear subject-specific lens but also allows a systemic perspective, which can serve as a model for other areas of chemistry and other natural sciences at universities.
Effects of ACLY Inhibition on Body Weight Distribution: A Drug Target Mendelian Randomization Study
2024-08-12

Background: Adenosine triphosphate-citrate lyase (ACLY) inhibition has proven clinically efficacious for low-density lipoprotein cholesterol (LDL-c) lowering and cardiovascular disease (CVD) risk reduction. Clinical and genetic evidence suggests that some LDL-c lowering strategies, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition with statin therapy increase body weight and the risk of developing type 2 diabetes mellitus (T2DM). However, whether ACLY inhibition affects metabolic risk factors is currently unknown. We aimed to investigate the effects of ACLY inhibition on glycaemic and anthropometric traits using Mendelian randomization (MR). Methods: As genetic instruments for ACLY inhibition, we selected weakly correlated single-nucleotide polymorphisms at the ACLY gene associated with lower ACLY gene expression in the eQTLGen study (N = 31,684) and lower LDL-c levels in the Global Lipid Genetic Consortium study (N = 1.65 million). Two-sample Mendelian randomization was employed to investigate the effects of ACLY inhibition on T2DM risk, and glycaemic and anthropometric traits using summary data from large consortia, with sample sizes ranging from 151,013 to 806,834 individuals. Findings for genetically predicted ACLY inhibition were compared to those obtained for genetically predicted HMGCR inhibition using the same instrument selection strategy and outcome data. Results: Primary MR analyses showed that genetically predicted ACLY inhibition was associated with lower waist-to-hip ratio (β per 1 standard deviation lower LDL-c: −1.17; 95% confidence interval (CI): −1.61 to −0.73; p &lt; 0.001) but not with risk of T2DM (odds ratio (OR) per standard deviation lower LDL-c: 0.74, 95% CI = 0.25 to 2.19, p = 0.59). In contrast, genetically predicted HMGCR inhibition was associated with higher waist-to-hip ratio (β = 0.15; 95%CI = 0.04 to 0.26; p = 0.008) and T2DM risk (OR = 1.73, 95% CI = 1.27 to 2.36, p &lt; 0.001). The MR analyses considering secondary outcomes showed that genetically predicted ACLY inhibition was associated with a lower waist-to-hip ratio adjusted for body mass index (BMI) (β = −1.41; 95%CI = −1.81 to −1.02; p &lt; 0.001). In contrast, genetically predicted HMGCR inhibition was associated with higher HbA1c (β = 0.19; 95%CI = 0.23 to 0.49; p &lt; 0.001) and BMI (β = 0.36; 95%CI = 0.23 to 0.49; p &lt; 0.001). Conclusions: Human genetic evidence supports the metabolically favourable effects of ACLY inhibition on body weight distribution, in contrast to HMGCR inhibition. These findings should be used to guide and prioritize ongoing clinical development efforts.
What is the exchange-repulsion energy? Insight by partitioning into physically meaningful contributions
2024-08-12

Exchange repulsion, the dominant repulsive contribution to intermolecular interaction energies, is caused by the Pauli principle, which enforces that electrons with the same spin must not be located at the same place. Starting from the Heitler-London expression of the exchange-repulsion energy, Exr, we investigate how it can be partitioned into physically relevant and comprehensible contributions. We demonstrate that a division of Exr into a positive kinetic and a negative potential part is possible. However, these contributions correlate only poorly with the actual exchange-repulsion energy. A meaningful partitioning of Exr is derived, where the kinetic energy contribution belongs to a term that vanishes for exact Hartree-Fock wave functions. The remaining pure potential energy terms are distinguished into an exchange integral contribution, Exi, as well as contributions to the repulsion-energy with two, three and four orbital indices (Exr2, Exr3, and Exr4). Qualitative explanations of these terms and their physical origin are proposed. The forms, relationships and absolute sizes of the four parts of Exr suggest an intuitive partitioning of the exchange-repulsion energy into orbital-pair contributions. Insight into the analytic form and quantitative size of the contributions to Exr is provided by considering the 3Sigma+u (1sigma g 1sigma u) state of the H2 molecule, the water dimer, as well as an argon atom interacting with Cl2 and N2. It is demonstrated that Exr is best described as a contribution due to the potential energy and that its leading contribution, Exr2, provides an intuitive qualitative and quantitative approach towards the exchange-repulsion energy.
Proteotoxicity and Apical Toxicity of Nicosulfuron to Danio rerio Embryos: A Comprehensive Assessment at Different Temperatures and pH
2024-08-12

In the present study, the toxicity of nicosulfuron to Danio rerio embryos was evaluated in three experiments through standardized toxicity tests according to OECD TG236 guidelines. In the first experiment, six concentrations of nicosulfuron (0, 0.1, 1, 10, 100, 1000 mg/L) were tested under optimal conditions (26 °C, pH 7.0) to assess the general sensitivity of zebrafish embryos to nicosulfuron. The second and third experiment examined the effects of different pH levels (5.0 and 9.0) and temperatures (21 °C and 31 °C) on the toxicity at four nicosulfuron concentrations (0, 10, 100, 1000 mg/L). Additionally, the sub-organismic effects of nicosulfuron on stress protein levels (Hsp70) of fish embryos were analyzed. Throughout the embryo experiments, no malformations were observed in all experiments. The survival rate exceeded 80% in all groups except for the 21 °C (pH 7.0) treatment groups. No significant effect of nicosulfuron on the survival rate was found at the same temperature or pH (p &gt; 0.05). No significant difference in the heart rate was found among all nicosulfuron groups (p &gt; 0.05) at 21 °C. The heart rate of fish embryos at 31 °C, pH 5.0 and pH 9.0 increased with nicosulfuron concentrations. Except for the pH 5.0 (26 °C) and 21 °C (pH 7.0) treatment groups, nicosulfuron was found to increase the hatching rate of embryos in other treatments; however, the corresponding times of action were different. At 21 °C (pH 7.0), the embryos did not hatch until 144 h post-fertilization. In terms of proteotoxicity, nicosulfuron was found to be more toxic to zebrafish embryos in the 21 °C, pH 5.0 and pH 9.0 treatment groups. However, at 31 °C, no significant difference in Hsp70 levels was found among all the different nicosulfuron concentrations (p &gt; 0.05). Our results show that nicosulfuron exerts a weak toxicity to zebrafish embryos; however, this toxicity is amplified by inappropriate pH or temperature conditions.
Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis
2024-08-12

Amyloid beta (Aβ) plays a major role in the pathogenesis of Alzheimer’s disease and, more recently, has been shown to protect against liver fibrosis. Therefore, we studied Aβ-42 levels and the expression of genes involved in the generation, degradation, and transport of Aβ proteins in liver samples from patients at different stages of metabolic dysfunction-associated liver disease (MASLD) and under steatotic conditions in vitro/in vivo. Amyloid precursor protein (APP), key Aβ-metabolizing proteins, and Aβ-42 were analyzed using RT-PCR, Western blotting, Luminex analysis in steatotic in vitro and fatty liver mouse models, and TaqMan qRT-PCR analysis in hepatic samples from patients with MASLD. Hepatocytes loaded with palmitic acid induced APP, presenilin, and neprilysin (NEP) expression, which was reversed by oleic acid. Increased APP and NEP, decreased BACE1, and unchanged Aβ-42 protein levels were found in the steatotic mouse liver compared to the normal liver. Aβ-42 concentrations were low in MASLD samples of patients with moderate to severe fibrosis compared to the livers of patients with mild or no MASLD. Consistent with the reduced Aβ-42 levels, the mRNA expression of proteins involved in APP degradation (ADAM9/10/17, BACE2) and Aβ-42 cleavage (MMP2/7/9, ACE) was increased. In the steatotic liver, the expression of APP- and Aβ-metabolizing proteins is increased, most likely related to oxidative stress, but does not affect hepatic Aβ-42 levels. Consistent with our previous findings, low Aβ-42 levels in patients with liver fibrosis appear to be caused by the reduced production and enhanced non-amyloidogenic processing of APP.
Day-to-day fluctuations in motivation drive effort-based choices
2024-08-12

Internal states like motivation fluctuate substantially over time. However, studies of the neurocomputational mechanims of motivated behaviour have failed to capture this. Here, we examined how naturalistic ups and downs in state motivation influence the subjective value of reward and effort. In a novel microlongitudinal design (N=155, state timepoints=3344, decision-making tasks=845), we captured fluctuations in state and effort-based decision-making using smartphone-based, momentary assessments as people went about their daily lives. We found that both state and trait have independent and multiplicative effects on decision-making. State-behaviour coupling was particularly pronounced in individuals with higher trait apathy, meaning that their choices were even more state dependent. Using computational modelling, we demonstrate that state motivation prospectively boosted reward sensitivity, making people more willing to exert effort in future. Our results show that day-to-day fluctuations in state and cognition are tightly linked and critical for understanding fundamental human behaviours and mental ill-health.
Persulfate activation by biochar and iron: Effect of chloride on formation of reactive species and transformation of N,N-diethyl-m-toluamide (DEET)
2024-08-13

Fenton-like processes using persulfate for oxidative water treatment and contaminant removal can be enhanced by the addition of redox-active biochar, which accelerates the reduction of Fe(III) to Fe(II) and increases the yield of reactive species that react with organic contaminants. However, available data on the formation of non-radical or radical species in the biochar/Fe(III)/persulfate system are inconsistent, which limits the evaluation of treatment efficiency and applicability in different water matrices. Based on competition kinetics calculations, we employed different scavengers and probe compounds to systematically evaluate the effect of chloride in presence of organic matter on the formation of major reactive species in the biochar/Fe(III)/persulfate system for the transformation of the model compound N,N‐diethyl-m-toluamide (DEET) at pH 2.5. We show that the transformation of methyl phenyl sulfoxide (PMSO) to methyl phenyl sulfone (PMSO<sub>2</sub>) cannot serve as a reliable indicator for Fe(IV), as previously suggested, because sulfate radicals also induce PMSO<sub>2</sub> formation. Although the formation of Fe(IV) cannot be completely excluded, sulfate radicals were identified as the major reactive species in the biochar/Fe(III)/persulfate system in pure water. In the presence of dissolved organic matter, low chloride concentrations (0.1 mM) shifted the major reactive species likely to hydroxyl radicals. Higher chloride concentrations (1 mM), as present in a mining-impacted acidic surface water, resulted in the formation of another reactive species, possibly Cl<sub>2</sub><sup>•-</sup>, and efficient DEET degradation. To tailor the application of this oxidation process, the water matrix must be considered as a decisive factor for reactive species formation and contaminant removal.
Aperiodic activity indexes neural hyperexcitability in generalized epilepsy
2024-08-13

Generalized epilepsy (GE) encompasses a heterogenous group of hyperexcitability disorders that clinically manifest as seizures. At the whole-brain level, distinct seizure patterns as well as interictal epileptic discharges (IEDs) reflect key signatures of hyperexcitability in magneto- and electroencephalographic (M/EEG) recordings. Moreover, it had been suggested that aperiodic activity, specifically the slope of the 1/ƒ x decay function of the power spectrum, might index neural excitability. However, it remained unclear if hyperexcitability as encountered at the cellular level directly translates to putative large-scale excitability signatures, amenable to M/EEG. In order to test whether the power spectrum is altered in hyperexcitable states, we recorded resting state MEG from male and female GE patients (n = 51; 29 females; 28.82 ± 12.18 years; mean ± SD) and age-matched healthy controls (n = 49; 22 females; 32.10 ± 12.09 years). We parametrized the power spectra using FOOOF to separate oscillatory from aperiodic activity to directly test whether aperiodic activity is systematically altered in GE patients. We further identified IEDs to quantify the temporal dynamics of aperiodic activity around overt epileptic activity. The results demonstrate that aperiodic activity indexes hyperexcitability in GE at the whole-brain level, especially during epochs when no IEDs were present (p = 0.0130, d = 0.52). Upon IEDs, large-scale circuits transiently shifted to a less excitable network state (p = 0.001, d = 0.68). In sum, these results uncover that MEG background activity might index hyperexcitability based on the current brain state and does not rely on the presence of epileptic waveforms. Significance Statement It had long been suspected that electric brain activity is systematically altered in hyperexcitability disorders, such as epilepsy. To date, it remained unclear how pathologic aperiodic activity can be quantified. Kopf et al. demonstrate that aperiodic MEG activity indexes neural hyperexcitability, especially when epileptic discharges were absent; hence, providing a novel non-invasively biomarker that possibly reflects neural excitability at the level of whole-brain recordings.
Major overlap in plant and soil organic carbon hotspots across Africa
2024-08-13

Terrestrial plant and soil organic carbon stocks are critical for regulating climate change, enhancing soil fertility, and supporting biodiversity. While a global-scale decoupling between plant and soil organic carbon has been documented, the hotspots and interconnections between these two carbon compartments across Africa, the second-largest continent on the planet, have been significantly overlooked. Here, we have compiled over 10,000 existing soil organic carbon observations to generate a high-resolution map, illustrating the distribution pattern of soil organic carbon in Africa. We then showed that above- and below-ground plant carbon are significantly and positively correlated with soil organic carbon across Africa. Both soil and plant carbon compartments shared major hotspots in the tropical regions. Our study provides critical insights into the spatial distribution of carbon hotspots across Africa, essential for soil conservation and safeguarding terrestrial carbon stocks amidst the challenges of climate change.
Singlet Fission in a Binary System: Effect of Structural Changes and Temperature
2024-08-13

Singlet fission is a promising mechanism to boost the performance of solar cells. In order to establish efficient singlet fission, it is essential to understand and control competing decay channels such as the occupation of trap states and the formation of excimers, for which the local ordering of the molecules plays an essential role. To systematically explore effects of molecular packing, a promising strategy is to blend the material of interest with another molecular compound. In the present study, we investigate binary thin films of anthradithiophene (ADT) and the high bandgap molecule hexaphenylbenzene with different compound ratios. By utilizing X-ray diffraction techniques and steady state optical spectroscopy, we identify a phase separating regime where the structural quality can be systematically tuned. Combining these subtle structural modifications with time-resolved and temperature-dependent photoluminescence spectroscopy allows us to independently manipulate the energetic landscape and thermal activation of kinetic processes. Eventually, our findings enable us to refine current models of the excited-state photophysics of ADT, suggesting that singlet fission critically depends on the number of neighboring ADT molecules, whereas excimer formation is not significantly affected by mesostructural changes. We propose that control of mesostructure and temperature can be a pathway toward controlling the balance between singlet fission and other competing channels.