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Mutualistic interactions benefit both partners, promoting coexistence and genetic diversity. Spatial structure can promote cooperation, but spatial expansions may also make it hard for mutualistic partners to stay together, because genetic drift at the expansion front creates regions of low genetic and species diversity. To explore the antagonism between mutualism and genetic drift, we grew cross-feeding strains of the budding yeast Saccharomyces cerevisiae on agar surfaces as a model for mutualists undergoing spatial expansions. By supplying varying amounts of the exchanged nutrients, we tuned strength and symmetry of the mutualistic interaction. Strong mutualism suppresses genetic demixing during spatial expansions and thereby maintains diversity, but weak or asymmetric mutualism is overwhelmed by genetic drift even when mutualism is still beneficial, slowing growth and reducing diversity. Theoretical modeling using experimentally measured parameters predicts the size of demixed regions and how strong mutualism must be to survive a spatial expansion.

We assessed morningness–eveningness in teachers and its relationship with sense of coherence and with burnout. The sense of coherence (SOC) is a major factor in determining how well a person manages stress and stays healthy. Burnout is defined as a three-component syndrome of emotional exhaustion, depersonalization, and low personal accomplishment. In study I, 73 primary school teachers (16 men, 57 women, mean age: 41.27 ± 11.50 years) filled the Composite Scale of Morningness (CSM) and the SOC. Morning oriented teachers reported a higher total SOC. Comprehensibility and manageability were positively related to morningness. In study II, 177 teachers (48 men, 128 women, 1 not specified, mean age: 46.0 ± 11.21 years) filled the CSM and the Maslach Burnout Inventory. Morning oriented teachers had a lower emotional exhaustion. Correlation coefficients were higher in the morning affect. Personal accomplishment was positively related to morningness. These studies suggest that morningness is an influential predictor of well-being in teachers.

Biological membranes constitute a critical component in all living cells. In addition to providing a conducive environment to a wide range of cellular processes, including transport and signaling, mounting evidence has established active participation of specific lipids in modulating membrane protein function through various mechanisms. Understanding lipid–protein interactions underlying these mechanisms at a sufficiently high resolution has proven extremely challenging, partly due to the semi-fluid nature of the membrane. In order to address this challenge computationally, multiple methods have been developed, including an alternative membrane representation termed highly mobile membrane mimetic (HMMM) in which lateral lipid diffusion has been significantly enhanced without compromising atomic details. The model allows for efficient sampling of lipid–protein interactions at atomic resolution, thereby significantly enhancing the effectiveness of molecular dynamics simulations in capturing membrane-associated phenomena. In this review, after providing an overview of HMMM model development, we will describe briefly successful application of the model to study a variety of membrane processes, including lipid-dependent binding and insertion of peripheral proteins, the mechanism of phospholipid insertion into lipid bilayers, and characterization of optimal tilt angle of transmembrane helices. We conclude with practical recommendations for proper usage of the model in simulation studies of membrane processes.

Intracellular transport is based on molecular motors that pull cargos along cytoskeletal filaments. One motor species always moves in one direction, e.g., conventional kinesin moves to the microtubule plus end, whereas cytoplasmic dynein moves to the microtubule minus end. However, many cellular cargoes are observed to move bidirectionally, involving both plus- and minus-end-directed motors. The presumably simplest mechanism for such bidirectional transport is provided by a tug-of-war between the two motor species. This mechanism is studied theoretically using the load-dependent transport properties of individual motors as measured in single-molecule experiments. In contrast to previous expectations, such a tug-of-war is found to be highly cooperative and to exhibit seven different motility regimes depending on the precise values of the single motor parameters. The sensitivity of the transport process to small parameter changes can be used by the cell to regulate its cargo traffic.

The investigation of ultrafast electronic and structural dynamics in low-dimensional systems such as nanowires and two-dimensional materials requires femtosecond probes providing high spatial resolution and strong interaction with small volume samples. Low-energy electrons exhibit large scattering cross-sections and high sensitivity to electric fields, but their pronounced dispersion during propagation in vacuum so far prevented their use as femtosecond probe pulses in time-resolved experiments. Here, employing a laser-triggered point-like source of either divergent or collimated electron wave packets, we developed a hybrid approach for femtosecond point projection microscopy and femtosecond low-energy electron diffraction. We investigate ultrafast electric currents in nanowires with sub-100 femtosecond temporal and few 10 nm spatial resolutions, and demonstrate the potential of our approach for studying structural dynamics in crystalline single-layer materials. Femtosecond low-energy electron pulses allow probing ultrafast processes in nanoscale systems with high spatial and temporal resolution. Here, the authors develop a hybrid approach for studying ultrafast electric currents and structural dynamics in low-dimensional systems.

Background: Dissecting the complex genetic basis of hypertrophic cardiomyopathy (HCM) may be key to both better understanding and optimally managing this most prevalent genetic cardiovascular disease. An array-based resequencing (ABR) assay was developed to facilitate genetic testing in HCM. Methods: An Affymetrix resequencing array and a single long-range PCR protocol were developed to cover the 3 most commonly affected genes in HCM, MYH7 (myosin, heavy chain 7, cardiac muscle, beta), MYBPC3 (myosin binding protein C, cardiac), and TNNT2 [troponin T type 2 (cardiac)]. Results: The assay detected the underlying point mutation in 23 of 24 reference samples and provided pointers toward identifying a G insertion and a 3-bp deletion. The comparability of array-based assay results to conventional capillary sequencing was ≥99.9%. Both techniques detected 1 heterozygous variant that was missed by the other method. Conclusions: The data provide evidence that ABR can substantially reduce the high workload previously associated with a genetic test for HCM. Therefore, the HCM array could facilitate large-scale studies aimed at broadening the understanding of the genetic and phenotypic diversity of HCM and related cardiomyopathies.

The Mediator kinase module regulates eukaryotic transcription by phosphorylating transcription-related targets and by modulating the association ofMediator and RNA polymerase II. The activity of its catalytic core, cyclin-dependent kinase 8 (CDK8), is controlled by Cyclin C and regulatory subunit MED12, with its deregulation contributing to numerous malignancies. Here, we combine in vitro biochemistry, cross-linking coupled to mass spectrometry, and in vivo studies to describe the binding location of the N-terminal segment of MED12 on the CDK8/Cyclin C complex and to gain mechanistic insights into the activation of CDK8 by MED12. Our data demonstrate that the N-terminal portion of MED12 wraps around CDK8, whereby it positions an “activation helix” close to the T-loop of CDK8 for its activation. Intriguingly, mutations in the activation helix that are frequently found in cancers do not diminish the affinity of MED12 for CDK8, yet likely alter the exact positioning of the activation helix. Furthermore, we find the transcriptome-wide gene-expression changes in human cells that result from a mutation in the MED12 activation helix to correlate with deregulated genes in breast and colon cancer. Finally, functional assays in the presence of kinase inhibitors reveal that binding of MED12 remodels the active site of CDK8 and thereby precludes the inhibition of ternary CDK8 complexes by type II kinase inhibitors. Taken together, our results not only allowus to propose a revised model of how CDK8 activity is regulated by MED12, but also offer a path forward in developing small molecules that target CDK8 in its MED12-bound form.

The durability of vaccine-induced immunity is often limited by waning responses, antigenic drift, and anti-vector immunity, highlighting the need for innovative vaccination strategies. Heterologous prime–boost approaches can help overcome these barriers by exploiting the complementary strengths of distinct platforms. Here, we evaluated a replication-deficient Orf virus-based spike vaccine (ORFV-S) in combination with the licensed Ad26 vector vaccine Jcovden (Ad26.COV2.S), using SARS-CoV-2 model. In a clinically aligned intramuscular immunogenicity screen in mice, Jcovden induced strong early anti-spike antibody responses but showed limited boostability, whereas ORFV-S was highly boost-responsive. Mixed regimens outperformed both homologous schedules. ORFV-S prime followed by Jcovden boost elicited the highest spike-binding antibody titers and vigorous CD4 + and CD8 + T-cell responses with a dominant Th1 profile. In the reverse regimen, ORFV-S boost improved inhibition across multiple SARS-CoV-2 variants, including immune-evasive strains and indicated qualitative improvements in the response breadth. Together, these findings suggest that sequence-dependent effects allow heterologous schedules to emphasize either cellular or humoral arms of the adaptive response.

Heterologous prime–boost vaccination has emerged as a promising approach to enhance immune responses by combining vaccines with complementary mechanisms of antigen delivery and immune activation. Here, we evaluated the immunogenicity of heterologous regimens combining the licensed inactivated SARS-CoV-2 vaccine (VLA2001) with the replication-deficient Orf virus-based vector vaccine (Prime-2-CoV). Using a mouse model, we compared these regimens to homologous vaccinations with each vaccine alone. Among the combinations tested, priming with VLA2001 followed by boosting with Prime-2-CoV induced the strongest spike-specific antibody responses, superior ACE2-binding inhibition against pre-Omicron variants, and robust Th1-biased immunity, with robust CD4 + and CD8 + T-cell responses. This sequence also enhanced nucleocapsid-specific immunity, underscoring the benefit of multiantigen targeting. These findings highlight the immunological synergy between inactivated whole-virus and ORFV vector vaccines and support the strategic use of Prime-2-CoV as a potent heterologous booster. The ORFV platform’s favorable safety profile and Th1-polarizing capacity make it a valuable candidate for future heterologous vaccine strategies beyond SARS-CoV-2.

Type IV pili are ubiquitous bacterial motors that power surface motility. In peritrichously piliated species, it is unclear how multiple pili are coordinated to generate movement with directional persistence. Here we use a combined theoretical and experimental approach to test the hypothesis that multiple pili of Neisseria gonorrhoeae are coordinated through a tug-of-war. Based on force-dependent unbinding rates and pilus retraction speeds measured at the level of single pili, we build a tug-of-war model. Whereas the one-dimensional model robustly predicts persistent movement, the two-dimensional model requires a mechanism of directional memory provided by re-elongation of fully retracted pili and pilus bundling. Experimentally, we confirm memory in the form of bursts of pilus retractions. Bursts are seen even with bundling suppressed, indicating re-elongation from stable core complexes as the key mechanism of directional memory. Directional memory increases the surface range explored by motile bacteria and likely facilitates surface colonization. Bacteria such as Neisseria gonorrhoeae use filamentous appendages known as pili to move on surfaces. Here, using a combined theoretical and experimental approach, the authors show that pili are coordinated through a tug-of-war mechanism that provides directional persistence.