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DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.

Traditional methods of biodiversity monitoring are often logistically challenging, time‐consuming, require experienced experts on species identification, and sometimes include destruction of the targeted specimens. Here, we investigated a non‐invasive approach of combining the use of drones and environmental DNA (eDNA) to monitor insect biodiversity on vegetation. We aimed to assess the efficiency of this novel method in capturing insect diversity and comparing insect composition across different vegetation types (grassland, shrub and forest) in Switzerland. A commercial, off‐the‐shelf drone was equipped with a specialised probe that autonomously swabbed vegetation and collected eDNA. Then, samples were processed using rapid third‐generation Oxford Nanopore sequencing. The obtained data were analysed for insect diversity, comparing taxonomic richness, evenness and community composition across the three habitat types using statistical techniques. Sequencing of the samples yielded 76 hexapod taxa, revealing an insect community with notable differences in taxonomic richness but not in evenness across grassland, shrub and forest habitats. Our study demonstrates the potential of drone‐based sampling integrated with eDNA and nanopore sequencing for biodiversity monitoring, offering a non‐destructive method for detecting insect occurrence on plant surfaces. Integrating robotics and eDNA technology provides a promising solution for fast, large‐scale, non‐invasive biodiversity monitoring, potentially improving conservation efforts and ecosystem management. We developed a novel method combining drone‐based sampling and environmental DNA (eDNA) with Oxford Nanopore sequencing to monitor insect biodiversity on vegetation. Using a DJI Matrice 3 drone, we collected eDNA samples from grassland, shrub and forest habitats in Switzerland, detecting 64 insect taxa and revealing habitat‐specific differences in diversity. This approach offers a non‐invasive, scalable solution for biodiversity monitoring, enhancing conservation and ecosystem management efforts.

The ability of environmental DNA (eDNA) to provide rapid assessments of mammal taxa composition at the watershed scale can make it an efficient survey method on large‐scale landscapes, complementing camera traps. Due to the rugged and inaccessible terrain of many areas in Bhutan, camera trapping is associated with logistical challenges, increasing the cost of sampling considerably. In this study, conducted in the Upper Punatsangchhu catchment basin of Bhutan, we investigated the ability of eDNA water samples to capture the diversity of terrestrial mammals in comparison with camera trapping, using six watersheds within the basin as a baseline sampling frame. Combined, the two methods detected a total of 72 mammalian species: eDNA metabarcoding identified 60 species, while camera trapping detected 33 species, with an overlap of 21 species between the two methods. In addition, eDNA metabarcoding detected 90% of the IUCN Red List species detected by the camera traps. Small mammals were frequently detected using eDNA metabarcoding, while camera trapping more often detected large mammals. The mean detection probabilities recorded from eDNA were higher for all species grouped by orders and size categories compared with camera trapping. Biodiversity models based on eDNA metabarcoding and camera trapping both retrieved dominant effects of temperature and isolation in structuring the mammal assemblage. We conclude that eDNA sampling based on watersheds accurately represents the spatial distribution of species across each watershed in our study area in Bhutan to provide a rapid assessment of mammals from river water.

Biodiversity monitoring in difficult‐to‐access areas, such as rugged mountain ranges, is currently challenging and thus often absent. Environmental DNA (eDNA) offers new opportunities to monitor remote or strictly protected areas, as rivers integrate the biodiversity information of entire catchments. Environmental samples can be analyzed either with metabarcoding or using species‐specific assays. Species‐specific assays like quantitative polymerase chain reaction assays do not require a fully‐equipped laboratory and thus can be used in settings with limited resources and are especially suited to monitoring elusive or threatened species of management concern. Recently developed molecular tools, such as CRISPR‐based diagnostic systems (CRISPR‐Dx), provide new avenues to facilitate eDNA analysis through species‐specific assays. Here, we combine multispecies primers with CRISPR‐Dx to detect terrestrial mammal species in parallel with one amplification to detect multiple species with CRISPR‐Dx. Given the short length of metabarcoding amplicons, designing species‐specific assays within them can be challenging. We designed species‐specific CRISPR‐Dx for eight terrestrial mammals within a commonly used metabarcoding amplicon ~59 base pairs in length and tested the assays on eDNA samples collected in high‐alpine catchments. Additionally, we compared the detections from CRISPR‐Dx with metabarcoding results of the same samples and with catchment‐based species inventories obtained through traditional monitoring. First, we show that designing species‐specific CRISPR‐Dx within a short amplicon allows terrestrial mammal detection in eDNA. Second, we demonstrate that CRISPR‐Dx assays combined with multispecies primers are comparable in sensitivity to metabarcoding and thus can bridge a gap between species‐specific assays and community analysis without requiring fully equipped laboratories. Third, we highlight that catchment‐based eDNA sampling can be used to monitor terrestrial mammals in remote or protected areas. Overall, we demonstrate that eDNA and particularly CRISPR‐Dx are a promising tool to monitor inaccessible and/or protected areas and to detect rare species across large spatiotemporal scales, thereby promoting biodiversity conservation. We combine multispecies primers with species‐specific CRISPR‐Dx—a method termed ampliscanning—to enable eDNA analysis without the need for a fully‐equipped laboratory and test our approach using water samples from high‐alpine catchments. By comparing our method to metabarcoding on the same extracts, we demonstrate that ampliscanning has a similar sensitivity. Additionally, we highlight that catchment‐based eDNA sampling can be effectively used to monitor terrestrial mammals in remote areas, such as rugged high‐alpine environments.

Recent reintroductions of the Eurasian beaver ( Castor fiber ) across Europe represents an ecological shift with potential implications for carbon cycling in stream corridors. However, the capacity of beaver impacts to influence short- and long-term carbon fluxes, and the mechanisms that govern these changes, remains poorly understood. We present a comprehensive carbon budget of a beaver-influenced stream corridor, covering all major aqueous and atmospheric exchanges, as well as biomass and sedimentary carbon storages, from a beaver wetland in Switzerland. By integrating carbon flux measurements with hydrology and bathymetry, we identify dominant pathways and dynamics in gaseous carbon emissions. Annually, the beaver wetland was a net carbon sink (98.3 ± 34.4 t yr -1 ), driven by subsurface removal of dissolved inorganic carbon. Carbon dioxide emissions were the dominant source of carbon loss, seasonally shifting the system to a net carbon source during summer water recession. Projecting the long-term sediment and deadwood storage following wetland infilling, our upper estimate of sequestered carbon was 1194 t (10.1 t ha -1 yr -1 ), nearly an order of magnitude greater than without beaver modification. Our findings demonstrate that beaver-induced hydrological change is fundamentally reshaping carbon cycling and reinforces the relevance of headwater catchments in climate change mitigation strategies. Beaver-induced hydrological change turned wetland into a net carbon sink with an approximate carbon storage of 100 tons per year, according to a comprehensive carbon budget analysis from a beaver wetland in Switzerland

In this paper, we studied the fate of endocytosed glycosylphosphatidyl inositol anchored proteins (GPI‐ APs) in mammalian cells, using aerolysin, a bacterial toxin that binds to the GPI anchor, as a probe. We find that GPI‐APs are transported down the endocytic pathway to reducing late endosomes in BHK cells, using biochemical, morphological and functional approaches. We also find that this transport correlates with the association to raft‐like membranes and thus that lipid rafts are present in late endosomes (in addition to the Golgi and the plasma membrane). In marked contrast, endocytosed GPI‐APs reach the recycling endosome in CHO cells and this transport correlates with a decreased raft association. GPI‐APs are, however, diverted from the recycling endosome and routed to late endosomes in CHO cells, when their raft association is increased by clustering seven or less GPI‐APs with an aerolysin mutant. We conclude that the different endocytic routes followed by GPI‐APs in different cell types depend on the residence time of GPI‐APs in lipid rafts, and hence that raft partitioning regulates GPI‐APs sorting in the endocytic pathway.

Since 2014, the Swiss Hepatitis Strategy (SHS) has targeted the elimination of Hepatitis C Virus (HCV) in Switzerland. The epidemiology of HCV is diverse across Swiss cantons, therefore cantonal-level screening and treatment strategies should be developed. This study aimed to identify scenarios to achieve HCV elimination in the canton of Bern by 2030. A preexisting Markov disease burden model was populated with data for Bern, and used to forecast the current and future prevalence of HCV, annual liver-related deaths (LRDs), and incidence of hepatocellular carcinoma and decompensated cirrhosis until 2030. Scenarios were developed to assess the current standard of care and potential long-term impact of the COVID-19 crisis on the HCV infected population. Additionally, potential scenarios for achieving the WHO 2030 targets and the SHS 2025 and 2030 targets (reduction of new cases of HCV, HCV-related mortality and viremic HCV cases) were identified. In 2019, there were an estimated 4,600 (95% UI: 3,330-4,940) viremic infections in the canton of Bern and 57% (n = 2,600) of viremic cases were diagnosed. This modelling forecasted a 10% increase in LRDs (28 in 2020 to 31 in 2030) with the current standard of care and a 50% increase in LRDs in a scenario assuming long-term delays. To achieve the WHO and SHS targets, the canton of Bern needs to increase the annual number of patients diagnosed (from 90 in 2019 to 250 per year in 2022-2024 [WHO], or 500 per year in 2022-2025 [SHS]) and treated (from 130 in 2019 to 340 per year in 2022-2024 [WHO] or 670 per year in 2022-2025 [SHS]). The SHS goals and the WHO targets for HCV elimination can be achieved in the Swiss canton of Bern by 2030; however, not at the current pace of screening, linkage to care and treatment.

Background Legionnaires’ disease (LD) is a severe form of primarily community-acquired pneumonia (CAP). To confirm a Legionella infection, microbiological testing is required. The Swiss and European guidelines recommend LD testing for all hospitalised CAP patients. However, the low positivity rate of such routine testing (1.5–3%) raises concerns about its cost-effectiveness and clinical utility. In a setting where routine testing is recommended, this multicentre study evaluated the impact of LD testing on the clinical management of the infection and antimicrobial prescribing. Methods Data from medical records of 195 community-acquired LD (CALD) patients from 20 Swiss hospitals (August 2022–March 2024) were analysed. We assessed the clinical management of CALD, focusing on the impact of microbiological testing on antibiotic prescribing. The appropriateness of antibiotic choice and duration of treatment was assessed using a standardised pathway analysis approach. Factors associated with unsupported antibiotic prescribing were assessed using mixed-effects logistic regression analysis. Results Microbiological testing was initiated promptly, with results available within 24 h after presenting to the hospital for 85.1% and within 48 h for 92.3% of patients. Antibiotics with Legionella coverage were initiated in 88.2% of patients within 24 h of admission. A positive Legionella test influenced antibiotic prescribing: 97.9% of patients received antibiotics active against Legionella spp. , and 79.6% were prescribed appropriate and targeted monotherapy within 24 h of receiving the test result. Overall, 35.4% of patients were treated with antibiotics for a median of 4 days (IQR 3–4 days) longer than guidelines recommend (defined as > 10 days for immunocompetent or > 21 days for immunocompromised patients). Prolonged treatment was associated with CALD severity and antibiotic use > 2 days postdischarge (proxy for clinical stability reached). 38.5% of patients with impaired renal function received a suboptimal loading dose of levofloxacin. Conclusion Routine aetiological testing for LD has improved the clinical management of CALD by facilitating rapid detection of CALD cases and timely initiation of appropriate and targeted antibiotic therapy. Future antimicrobial stewardship efforts should sensitise physicians that a shorter duration of antibiotic treatment for CALD of 5 to 7 days according to the latest Swiss CAP guidelines is sufficient and safe.

Background Currently, Roux-en Y gastric bypass (RYGB) is the most efficient therapy for severe obesity. Weight loss after surgery is, however, highly variable and genetically influenced. Genome-wide association studies have identified several single nucleotide polymorphisms (SNP) associated with body mass index (BMI) and waist-hip ratio (WHR). We aimed to identify two genetic risk scores (GRS) composed of weighted BMI and WHR-associated SNPs to estimate their impact on excess BMI loss (EBMIL) after RYGB surgery. Methods Two hundred and thirty-eight obese patients (BMI 45.1 ± 6.2 kg/m 2 , 74 % women), who underwent RYGB, were genotyped for 35 BMI and WHR-associated SNPs and were followed up after 2 years. SNPs with high impact on post-surgical weight loss were filtered out using a random forest model. The filtered SNPs were combined into a GRS and analyzed in a linear regression model. Results An up to 11 % lower EBMIL with higher risk score was estimated for two GRS models ( P  = 0.026 resp. P  = 0.021) composed of seven BMI-associated SNPs (closest genes: MC4R , TMEM160 , PTBP2 , NUDT3 , TFAP2B , ZNF608 , MAP2K5 , GNPDA2 , and MTCH2 ) and of three WHR-associated SNPs (closest genes: HOXC13 , LYPLAL1 , and DNM3 - PIGC ). Patients within the lowest GRS quartile had higher EBMIL compared to patients within the other three quartiles in both models. Conclusions We identified two GRSs composed of BMI and WHR-associated SNPs with significant impact on weight loss after RYGB surgery using random forest analysis as a SNP selection tool. The GRS may be useful to pre-surgically evaluate the risks for patients undergoing RYGB surgery.

Switzerland has one of the highest annual Legionnaires’ disease (LD) notification rates in Europe (7.8 cases/100,000 population in 2021). The main sources of infection and the cause for this high rate remain largely unknown. This hampers the implementation of targeted Legionella spp. control efforts. The SwissLEGIO national case–control and molecular source attribution study investigates risk factors and infection sources for community-acquired LD in Switzerland. Over the duration of one year, the study is recruiting 205 newly diagnosed LD patients through a network of 20 university and cantonal hospitals. Healthy controls matched for age, sex, and residence at district level are recruited from the general population. Risk factors for LD are assessed in questionnaire-based interviews. Clinical and environmental Legionella spp. isolates are compared using whole genome sequencing (WGS). Direct comparison of sero- and sequence types (ST), core genome multilocus sequencing types (cgMLST), and single nucleotide polymorphisms (SNPs) between clinical and environmental isolates are used to investigate the infection sources and the prevalence and virulence of different Legionella spp. strains detected across Switzerland. The SwissLEGIO study innovates in combining case–control and molecular typing approaches for source attribution on a national level outside an outbreak setting. The study provides a unique platform for national Legionellosis and Legionella research and is conducted in an inter- and transdisciplinary, co-production approach involving various national governmental and national research stakeholders.