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Identifying the roles played by individual heterotrophic bacteria in the degradation of high molecular weight (HMW) substrates is critical to understanding the constraints on carbon cycling in the ocean. At five sites in the Atlantic Ocean, we investigated the processing of organic matter by tracking changes in microbial community composition as HMW polysaccharides were enzymatically hydrolysed over time. During this investigation, we discovered that a considerable fraction of heterotrophic bacteria uses a newly-identified ‘selfish’ mode of substrate processing. We therefore additionally examined the balance of individual substrate utilisation mechanisms at different locations by linking individual microorganisms to distinct substrate utilisation mechanisms. Through FISH and uptake of fluorescently-labelled polysaccharides, ‘selfish’ organisms were identified as belonging to the Bacteroidetes , Planctomycetes and Gammaproteobacteria . ‘Sharing’ (extracellular enzyme producing) and ‘scavenging’ (non-enzyme producing) organisms predominantly belonged to the Alteromonadaceae and SAR11 clades, respectively. The extent to which individual mechanisms prevail depended on the initial population structure of the bacterial community at a given location and time, as well as the growth rate of specific bacteria. Furthermore, the same substrate was processed in different ways by different members of a pelagic microbial community, pointing to significant follow-on effects for carbon cycling.

Understanding drop size distribution (DSD) variability has important implications for remote sensing and numerical modeling applications. Twelve disdrometer datasets across three latitude bands are analyzed in this study, spanning a broad range of precipitation regimes: light rain, orographic, deep convective, organized midlatitude, and tropical oceanic. Principal component analysis (PCA) is used to reveal comprehensive modes of global DSD spatial and temporal variability. Although the locations contain different distributions of individual DSD parameters, all locations are found to have the same modes of variability. Based on PCA, six groups of points with unique DSD characteristics emerge. The physical processes that underpin these groups are revealed through supporting radar observations. Group 1 (group 2) is characterized by high (low) liquid water content (LWC), broad (narrow) distribution widths, and large (small) median drop diameters D 0 . Radar analysis identifies group 1 (group 2) as convective (stratiform) rainfall. Group 3 is characterized by weak, shallow radar echoes and large concentrations of small drops, indicative of warm rain showers. Group 4 identifies heavy stratiform precipitation. The low latitudes exhibit distinct bimodal distributions of the normalized intercept parameter N w , LWC, and D 0 and are found to have a clustering of points (group 5) with high rain rates, large N w , and moderate D 0 , a signature of robust warm rain processes. A distinct group associated with ice-based convection (group 6) emerges in the midlatitudes. Although all locations exhibit the same covariance of parameters associated with these groups, it is likely that the physical processes responsible for shaping the DSDs vary as a function of location.

Background The risk of noncontact ACL injury reportedly is increased in patients with a greater posterior tibial slope (PTS), but clinical data are inconsistent. It is unclear whether the medial and lateral PTSs have a different impact on this connection. It also is unknown whether the meniscal slope (MS) is associated with ACL injury. Patients/methods Using MRI, we compared the medial and lateral PTSs and MSs separately in 55 matched pairs of patients with isolated noncontact ACL injuries and a control group. Results Neither the PTS nor the relative difference between the medial and lateral PTSs differed between groups. In contrast, the lateral MS was greater with ACL injuries: 2.0° versus −2.7° in males with and without ACL injury and 1.7° versus −0.9 in females. Uninjured females had a greater PTS than males: 4.9° versus 3.0° in females and males medially, respectively; 5.7° versus 4.0° lateral. Conclusions There is no obvious link between the medial or lateral PTSs and ACL injury, and there is no obvious link between the relative difference in the medial and lateral PTSs and noncontact ACL injury. However, a greater lateral MS may indicate a greater risk of injury. The PTS can differ between the genders but the average difference is small. Level of Evidence Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments.

There is an association between low socioeconomic status and chronic obstructive pulmonary disease (COPD), but it is not known whether this impacts on drug prescription for COPD treatment. The aim of the study was to explore whether drug prescription differs between COPD patients with low and high socioeconomic status. Data from patients with incident and prevalent COPD (age>40 years), without an asthma diagnosis, visiting primary care in 2021-2022 were extracted from The Swedish National Airway Register (SNAR) and linked to Swedish National Health registries. Socioeconomic status was assessed by educational level and annual income. Statistical analyses were conducted by means of chi square tests, together with post-hoc test. In total, 38692 patients (mean age 73.6 years, 55.5% women, FEV 59.5% of predicted value) were included. Subdivision into GOLD group A, B and E was possible in 29128 patients. Triple therapy (long-acting antimuscarinic antagonists, LAMA + long-acting beta-2-agonist, LABA + inhaled steroids, ICS), was more often prescribed in the low education group (observed/expected ratio 1.09; p<0.0001) and low income group (ratio 1.05; p<0.05) and less often in the high education group (ratio 0.87; p<0.0001) and high income group (ratio 0.88; p<0.0001). Monotherapy (LAMA) was more often prescribed in patients with high income (ratio 1.09; p<0.0001) and less often in patients with low income (ratio 0.93; p=0.0004). Differences between high and low education and income were driven by differences in group B. Prescription patterns were associated with small, statistically significant differences, between COPD patients with low and high socioeconomic status. Triple therapy was more often prescribed to patients with low socioeconomic status, and monotherapy with LAMA more often to patients with high. The reason for this is not clear but may be caused by differences in exacerbation rate between the socioeconomic groups.

Currently accepted fungal diagnostic techniques, such as culture, biopsy, and serology, lack rapidity and efficiency. Newer diagnostic methods, such as polymerase chain reaction (PCR)—based assays, have the potential to improve fungal diagnostics in a faster, more sensitive, and specific manner. Preliminary data indicate that, when PCR-based fungal diagnostic assays guide antifungal therapy, they may lower patient mortality and decrease unnecessary antifungal treatment, improving treatment-associated costs and avoiding toxicity. Moreover, newer PCR techniques can identify antifungal resistance DNA loci, but the clinical correlation between those loci and clinical failure has to be studied further. In addition, future studies need to focus on the implementation of PCR techniques in clinical decision making and on combining them with other diagnostic tests. A consensus on the standardization of PCR techniques, along with validation from large prospective studies, is necessary to allow widespread adoption of these assays.

While a large body of literature documents the impairing effect of anxiety on cognition, performing a demanding task was shown to be effective in reducing anxiety. Here we explored the mechanisms of this anxiolytic effect by examining how a pharmacological challenge designed to improve attentional processes influences the interplay between the neural networks engaged during anxiety and cognition. Using a double-blind between-subject design, we pharmacologically manipulated working memory (WM) using a single oral dose of 20 mg methylphenidate (MPH, cognitive enhancer) or placebo. Fifty healthy adults (25/drug group) performed two runs of a WM N-back task in a 3 T magnetic resonance imaging scanner. This task comprised a low (1-Back) and high (3-Back) WM load, which were performed in two contexts, safety or threat of shocks (induced-anxiety). Analyses revealed that (1) WM accuracy was overall improved by MPH and (2) MPH (vs. placebo) strengthened the engagement of regions within the fronto-parietal control network (FPCN) and reduced the default mode network (DMN) deactivation. These MPH effects predominated in the most difficult context, i.e., threat condition, first run (novelty of the task), and 3-Back task. The facilitation of neural activation can be interpreted as an expansion of cognitive resources, which could foster both the representation and integration of anxiety-provoking stimuli as well as the top–down regulatory processes to protect against the detrimental effect of anxiety. This mechanism might establish an optimal balance between FPCN (cognitive processing) and DMN (emotion regulation) recruitment.

The ‘KASCADE Cosmic ray Data Centre’ is a web portal (https://kcdc.ikp.kit.edu), where the data of the astroparticle physics experiment KASCADE-Grande are made available for the interested public. The KASCADE experiment was a large-area detector for the measurement of high-energy cosmic rays via the detection of extensive air showers. The multi-detector installations KASCADE and its extension KASCADE-Grande stopped the active data acquisition in 2013 after more than 20 years of data taking. In several updates since our first release in 2013 with KCDC we provide the public measured and reconstructed parameters of more than 433 million air showers. In addition, KCDC provides meta data information and documentation to enable a user outside the community of experts to perform their own data analysis. Simulation data from three different high energy interaction models have been made available as well as a compilation of measured and published spectra from various experiments. In addition, detailed educational examples shall encourage high-school students and early stage researchers to learn about astroparticle physics, cosmic radiation as well as the handling of Big Data and about the sustainable and public provision of scientific data.

The introduction of AlphaFold 2 1 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design 2 , 3 , 4 , 5 – 6 . Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein–ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein–nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody–antigen prediction accuracy compared with AlphaFold-Multimer v.2.3 7 , 8 . Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework. AlphaFold 3 has a substantially updated architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues with greatly improved accuracy over many previous specialized tools.

LOPES, the LOFAR prototype station, was an antenna array for cosmic-ray air showers operating from 2003 to 2013 within the KASCADE-Grande experiment. Meanwhile, the analysis is finished and the data of air-shower events measured by LOPES are available with open access in the KASCADE Cosmic Ray Data Center (KCDC). This article intends to provide a summary of the achievements, results, and lessons learned from LOPES. By digital, interferometric beamforming the detection of air showers became possible in the radio-loud environment of the Karlsruhe Institute of Technology (KIT). As a prototype experiment, LOPES tested several antenna types, array configurations and calibration techniques, and pioneered analysis methods for the reconstruction of the most important shower parameters, i.e., the arrival direction, the energy, and mass-dependent observables such as the position of the shower maximum. In addition to a review and update of previously published results, we also present new results based on end-to-end simulations including all known instrumental properties. For this, we applied the detector response to radio signals simulated with the CoREAS extension of CORSIKA, and analyzed them in the same way as measured data. Thus, we were able to study the detector performance more accurately than before, including some previously inaccessible features such as the impact of noise on the interferometric cross-correlation beam. These results led to several improvements, which are documented in this paper and can provide useful input for the design of future cosmic-ray experiments based on the digital radio-detection technique.