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Abstract The sophisticated envelope of Gram-negative bacteria modulates the uptake of small molecules in a side-chain-sensitive manner. Despite intensive theoretical and experimental investigations, a general set of pathways underpinning antibiotic uptake has not been identified. This manuscript discusses the passive influx versus active efflux of antibiotics, considering the responsible membrane proteins and the transported molecules. Recent methods have analyzed drug transport across the bacterial membrane in order to understand their activity. The combination of in vitro, in cellulo and in silico methods shed light on the key, mainly electrostatic, interactions between the molecule surface, porins and transporters during permeation. A key factor is the relationship between the dose of an active compound near its target and its antibacterial activity during the critical early window. Today, methodology breakthroughs provide fruitful tools to precisely dissect drug transport, identify key steps in drug resistance associated with membrane impermeability and efflux, and highlight key parameters to generate more effective drugs.

Amplicon sequencing has long served as a robust method for characterising microbial communities, and despite inherent resolution limitations, it remains a preferred technique, offering cost‐ and time‐effective insights into bacterial compositions. Here, we introduce ONT‐AmpSeq, a user‐friendly pipeline designed for processing amplicon sequencing data generated from Oxford Nanopore Technology (ONT) devices. Our pipeline enables efficient creation of taxonomically annotated operational taxonomic unit (OTU) tables from ONT sequencing data, with the flexibility to multiplex amplicons on the same barcode. The pipeline encompasses six main steps—statistics, quality filtering, alignment, clustering, polishing, and taxonomic classification—integrating various state‐of‐the‐art software tools. We provide a detailed description of each step, along with performance tests and robustness evaluations using both test data and a ZymoBIOMICS® Microbial Community Standard mock community dataset. Our results demonstrate the ability of ONT‐AmpSeq to effectively process ONT amplicon data, offering valuable insights into microbial community composition. Additionally, we discuss the influence of polishing tools on taxonomic insight and the impact of taxonomic annotation methods on the derived microbial composition. Overall, ONT‐AmpSeq represents a comprehensive solution for analysing ONT amplicon sequencing data, facilitating streamlined and reliable microbial community analysis. The pipeline, along with test data, is freely available for public use.

Abstract Background Komagataella phaffii (K. phaffii), formerly known as Pichia pastoris, is a widely utilized yeast for recombinant protein production. However, due to the formation of overflow metabolites, carbon yields may be reduced and product recovery becomes challenging. This study investigates the impact of oxygen availability, different glucose concentrations and feeding strategies on overflow metabolite formation and recombinant protein production in K. phaffii. Results High glucose concentrations in batch fermentation, as applied in literature, lead to substantial ethanol accumulation, adversely affecting biomass yield and product formation. Increasing dissolved oxygen setpoints does not significantly reduce ethanol formation, indicating that glucose surplus, rather than oxygen availability, drives overflow metabolism. Decreasing the initial glucose concentration to 5 g/L and adapting the feeding strategy of the fed-batch phase, effectively mitigates overflow metabolite formation, improving biomass yield by up to 9% and product concentration by 40% without increasing process time. Conclusions These findings underscore the importance of a suitable glucose-feeding strategy in K. phaffii fermentation processes and highlight the detrimental effects of overflow metabolites on productivity. By optimizing carbon source utilization, it is possible to enhance fermentation efficiency and recombinant protein production with K. phaffii.

The syntypes of Carychium reticulatum Hauffen, 1856 and Carychium bidentatum Hauffen, 1856, thought to be lost to science, have been rediscovered in a recent inventory of the shell collection of Domink Bilimek (1813–1884) at the University of Natural Resources and Life Sciences in Vienna, Austria (BOKU). In this work, we present (1) the historical context of the Dominik Bilimek and Heinrich (also: Henrik) Hauffen collections and (2) provide a contemporary image dataset of Hauffen’s original material while considering today’s taxonomic understanding of the genus Zospeum. We clarify the taxonomic status of the syntypes by using light microscopy, Scanning Electron Microcopy (SEM) and 3D X-ray Micro-CT data in conjunction with Hauffen’s original illustrations and compare them to contemporary investigations of their closest congeners. Analysis of Zospeum reticulatum (Hauffen, 1856) is supported by historical documentation from Heinrich Hauffen’s original annotations and Bilimek’s diary entries, as well as from individual collection labels in Hauffen’s own script (verified by archive material from the Archive of the National Museum of Slovenia, NMS). Hauffen’s descriptions are based on apertural morphology and shell microstructure. Our re-investigation of Zospeum reticulatum provides corroborating evidence supporting its assignment to Zospeum spelaeum (Rossmaessler, 1839) while that of Carychium bidentatum corroborates its status as junior synonym of Zospeum costatum (Freyer, 1855).

Water and contaminated hospital surfaces have been reported as major causes of Hospital acquirеd (nosocomial) infections (HAIs), a significant global safety problem for both patients and medical staff. However, the frequency of Intensive Care Units (ICU)-HAIs has been reported to be at least 2-3 times greater in low- to middle-income countries, particularly in Zimbabwe, than in high-income countries. Thus, this study aimed at determining the presence of pathogenic bacteria in water and surfaces from selected high-risk areas within the intensive care units of three hospitals (A, B, and C) in Harare, Zimbabwe. Water and surface samples were collected and processed within 24 hours of collection. The water samples were tested for the presence of microbial indicators using standard methodology of microbial plating. The surface swabs were also investigated using microbial plating. The organisms that were found to be present in surface samples were then identified using biochemical tests and 16S polymerase chain reaction (16S PCR). The results showed no bacteria present in any of the water samples tested during the study. However, using morphological characteristics, six different types of bacteria were identified in surface samples. The bacteria identified to be present on surfaces were Escherichia coli, Salmonella, Shigella, Staphylococcus, Pseudomonas, and Streptococcus. Hospital A surfaces may be the major cause of some bacterial infection outbreaks, hence, there is a need for better ways of reducing contamination of surfaces in the intensive care units.

Abstract The associative theory of creativity proposes that creative ideas result from connecting remotely related concepts in memory. Previous research found that higher creative individuals exhibit a more flexible organization of semantic memory, generate more uncommon word associations, and judge remote concepts as more related. In this study (N = 93), we used fMRI to investigate brain regions involved in judging the relatedness of concepts that vary in their semantic distance, and how such neural involvement relates to individual differences in creativity. Brain regions where activity increased with semantic relatedness mainly overlapped with default, control, salience, semantic control, and multiple demand networks. The default and semantic control networks exhibited increased involvement when evaluating more remote associations. Finally, higher creative people, who provided higher relatedness judgements on average, exhibited lower activity in those regions, possibly reflecting higher neural efficiency. We discuss these findings in the context of the neurocognitive processing underlying creativity. Overall, our findings indicate that judging remote concepts as related reflects a cognitive mechanism underlying creativity and shed light on the neural correlates of this mechanism.

One of the major setbacks in environmental restoration is how to promote the arrival of propagules in degraded areas, and this issue is intensified at sites without vegetation, where natural dispersal is limited. To overcome this issue, one of the methods employed is the use of artificial perches, intended for attracting seed-dispersing birds, providing perching sites, and thus, facilitating the formation of vegetation nuclei from the seeds that are excreted, regurgitated, or accidentally dropped. The aim of this study was to quantify and identify the birds that used the artificial perches in a degraded area on the margins of the Forqueta River, RS, Brazil, in order to evaluate their effectiveness as an ecological restoration method. Over one year, 11 bird species were observed to use the perches. Despite the presence of birds, there was no significant seed germination at the base of the perches. Absence of frugivorous species and adverse conditions of the soil might have contributed to this result. Previous studies showed diverging results on the effectiveness of artificial perches, indicating the need for considering several factors, such as availability of food resources and the presence of invasive species. The present study highlights the complexity of ecological processes involved in the restoration of degraded areas and the importance of adaptive approaches to reach effective results.

The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest. As more and more ligands for novel E3 ligases are discovered, the chemical effort to identify the best E3 ligase for a given target is exploding. Therefore, a genetic system to identify degradation-causing E3 ligases and suitable target/E3 ligase pairs is urgently needed. Here, we used the well-established dimerization of the FKBP12 protein and FRB domain by rapamycin to bring the target protein WDR5 into proximity with candidate E3 ligases. Strikingly, this rapamycin-induced proximity assay (RiPA) revealed that VHL, but not Cereblon, is able to induce WDR5 degradation - a finding previously made by PROTACs, demonstrating its predictive power. By optimizing the steric arrangement of all components and fusing the target protein with a minimal luciferase, RiPA can identify the ideal E3 for any target protein of interest in living cells, significantly reducing and focusing the chemical effort in the early stages of PROTAC development.

Abstract Myrciinae, one of the nine subtribes of Myrteae, is a monophyletic group and only includes Myrcia. Phylogenetic studies have culminated in the establishment of sections in this genus supported by floral morphological traits. The anatomy of reproductive organs in Myrteae has proven to be important for understanding the evolution in subtribes. We described the floral anatomy of 12 species of Myrcia in eight of the nine sections to identify characteristics that may be useful for species or section delimitation. Herbarium samples and freshly collected material were processed using standard anatomical techniques. Anatomical aspects in all floral whorls that were similar between the species studied, but may occur in species in other subtribes of Myrteae, are the monocyclic pattern of ovarian vascularization, an outer, median and inner parenchymatic ovarian mesophyll, homogeneous mesophyll in the sepal, and campylotropous ovule. Spongy parenchyma in the petal seems to be the most common pattern for Myrteae, but in Pliniinae, a sister subtribe of Myciinae, homogeneous mesophyll is the most frequent type. The discrete differences observed that should be further explored in the subtribe Myrciinae are the presence or absence of unicellular, non-glandular trichomes in the indumentum of the pedicel, gynoecium, hypanthium, sepal, and petal.

Chronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Similarly, the consequences of chronic HIV infection on the integrity of the female genital epithelium are poorly understood, despite its importance in HIV transmission and replication. Ectocervical biopsies were obtained from HIV-seropositive (n = 14) and HIV-seronegative (n = 47) female Kenyan sex workers. RNA sequencing and bioimage analysis of epithelial junction proteins (E-cadherin, desmoglein-1, claudin-1, and zonula occludens-1) were conducted, along with CD4 staining. RNA sequencing revealed upregulation of immunoregulatory genes in HIV-seropositive women, primarily associated with heightened T cell activity and interferon signaling, which further correlated with plasma viral load. Transcription factor analysis confirmed the upregulation of pro-inflammatory transcription factors, such as RELA, NFKB1, and IKZF3, which facilitates HIV persistence in T cells. Conversely, genes and pathways associated with epithelial barrier function and structure were downregulated in the context of HIV. Digital bioimage analysis corroborated these findings, revealing significant disruption of various epithelial junction proteins in ectocervical tissues of the HIV-seropositive women. Thus, chronic HIV infection associated with ectocervical inflammation, characterized by induced T cell responses and interferon signaling, coupled with epithelial disruption. These alterations may influence HIV transmission and heighten susceptibility to other sexually transmitted infections. These findings prompt exploration of therapeutic interventions to address HIV-related complications and mitigate the risk of sexually transmitted infection transmission.

Background This study investigated malaria epidemiology in Edo-North, Nigeria; a region within the equatorial rainforest belt that has lacked prior research on malaria prevalence. This research sought to investigate the prevalence of malaria and identify potential risk factors in Edo-North, Nigeria. Additionally, the study aimed to analyze trends in malaria cases to inform the development of effective malaria control measures. Methodology A cross-sectional study was conducted in six local government areas of Edo-North, Nigeria, between June and August 2023. Using systematic sampling, study zones, local governments, towns, villages, and households were selected. Data on sociodemographics and environmental risk factors were collected from 605 participants through questionnaires and blood samples. Blood smears were microscopically examined, binary and multivariate logistic regression was used for data analysis. Malaria disease rate trends were also analyzed from health records. Statistical analyses were performed using R software, with p-values less than 0.05 considered statistically significant. Results The overall malaria prevalence in the study area was 15.54%, with males more likely to be infected than females. Prevalence varied across localities, with Akoko-Edo having the highest rate. Children had the highest prevalence. Rural residents were more likely to have malaria than urban residents. Binary logistic regression identified several risk factors, including age, location, local government area, education, occupation, marital status, housing type, household size, water source, sanitation, surrounding environment, window net use, ceiling type, water storage, and parasite density. The multivariate logistic regression analysis identified several significant risk factors for malaria in the study population. Children, residents of Owan-East, individuals using pit latrines, and those not sleeping under LLINs were at significantly increased risk. Environmental factors such as proximity to bushes, streams/rivers, and storing water in open containers were also associated with higher malaria prevalence. History of malaria treatment at pharmacies and use of Chloroquine/Quinine medication were linked to recurrent infections. The study found a high average parasite density (5,146 parasites/μL) and low consistent LLIN use despite widespread ownership. Trend analysis from malaria records revealed a decline in malaria prevalence from 2020 to 2023. Conclusions The study identified several demographic, environmental and behavioural factors associated with malaria risk in Edo North. Males, children, urban dwellers, those living in mud houses and those in large households, proximity to natural features such as bushes, rivers and streams and low LLIN were more likely to contract malaria. These findings highlight the importance of implementing targeted interventions to address these risk factors and reduce the burden of malaria.

Summary: Impaired sleep is a common aspect of aging and often precedes the onset of Alzheimer’s disease. Here, we compare the effects of sleep deprivation in young wild-type mice and their APP/PS1 littermates, a murine model of Alzheimer’s disease. After 7 h of sleep deprivation, both genotypes exhibit an increase in EEG slow-wave activity. However, only the wild-type mice demonstrate an increase in the power of infraslow norepinephrine oscillations, which are characteristic of healthy non-rapid eye movement sleep. Notably, the APP/PS1 mice fail to enhance norepinephrine oscillations 24 h after sleep deprivation, coinciding with an accumulation of cerebral amyloid-β protein. Proteome analysis of cerebrospinal fluid and extracellular fluid further supports these findings by showing altered protein clearance in APP/PS1 mice. We propose that the suppression of infraslow norepinephrine oscillations following sleep deprivation contributes to increased vulnerability to sleep loss and heightens the risk of developing amyloid pathology in early stages of Alzheimer’s disease.

This study aims to determine the effectiveness of using the ARSINAPS mobile augmented reality application on learning motivation and outcomes in high school and biology education students. The method used in this study was quasi-experimental with a post-test control group design. The research sample consisted of two experimental classes and two control classes from three schools in the Jakarta, Bekasi, and Tangerang areas, totalling 140 students, and from the college level, consisting of one experimental class and one control class, totalling 68 students. The data obtained were in the form of learning outcomes in the respiratory system and learning motivation scores in biology learning. The average high school-level motivation score in the control class was 85.99, and the overall average for learning outcomes was 77.33 and 63.05. Based on the results of the data calculations, the application effectively improves students’ learning outcomes at the high school and undergraduate levels

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P

A prioritisation study was conducted to address the lack of adequate information about potential pests likely to be introduced in Zambia and become invasive. The study was conducted by subject matter experts from relevant institutions in and outside Zambia. Although this study focused on major pest categories, this paper only addresses bacteria and Protista. A list of 306 bacterial and 10 Protista species adjudged to affect plants was generated using CABI’s Horizon Scanning Tool. The 316 (total) pest species were refined to focus on pests that affect value chains important to Zambia’s economy. This resulted in a final list of 133 bacteria and eight Protista. Four additional bacteria species considered of phytosanitary interest were added and all 137 bacteria and eight Protista species were subjected to a rapid risk assessment using agreed guidelines. Vectors reported to transmit any of the pathogenic organisms were also subjected to a risk assessment. A proportion of 53% (n = 77 of 145) comprising 73 bacteria and four Protista species were reported as present in Africa. Of these, 42 (57%, n = 73) bacterial species and two (n=4) Protista species were reported in neighbouring countries. Considering a cut-off of 54, the highest scoring pests were 40 bacteria (highest score of 140) and three Protista (highest score of 125). Three actions were suggested for high-scoring pests, a detection surveillance, a pest-initiated pest risk analysis (PRA) or a detection surveillance followed by pest-initiated PRA. A “no action” was suggested where the risk was very low although, for some pathogenic organisms, a “no action” was followed by periodic monitoring. This information will contribute towards proactive prevention and management of biological invasions.

The bat Furipterus horrens (Cuvier, 1828) is endemic to the Neotropics, and in Brazil, it is widespread. However, there are few records in the Amazon Region where it is known only from the states of Amazonas and Pará. Here, we report the occurrence of a colony of F. horrens in an anthropogenic environment in the Brazilian Amazon. This type of habitat has not been previously reported for this species. We also compile and update the known occurrences of F. horrens in Brazil. Our new data brings to the number of localities for this species in Brazil to 76.

Background: The generation and perfusion of complex vascularized tissues in vitro requires sophisticated perfusion techniques. For multiscale arteriovenous networks, not only the arterial, but also the venous, biomechanical and biochemical conditions that physiologically exist in the human body must be accurately emulated. For this, we here present a modular arteriovenous perfusion system for the in vitro culture of a multi-scale bioartificial vascular network. Methods: The custom-built perfusion system consisted of two circuits: in the arterial circuit, physiological arterial biomechanical and biochemical conditions were simulated using a modular set-up with a pulsatile peristaltic pump, compliance chambers, and resistors. In the venous circuit, venous conditions were emulated accordingly. In the center of the system, a bioartificial multi-scale vascularized fibrin-based tissue was perfused by both circuits simultaneously under biomimetic arteriovenous conditions. Culture conditions were monitored continuously using a multi-sensor monitoring system. Results: The physiological arterial and venous pressure- and flow-curves, as well as the microvascular arteriovenous oxygen partial pressure gradient, were accurately emulated in the perfusion system. The multi-sensor monitoring system facilitated live monitoring of the respective parameters and data-logging. In a proof-of-concept experiment, vascularized three-dimensional fibrin tissues showed sustained cell viability and homogenous microvessel formation after culture in the perfusion system. Conclusions: The arteriovenous perfusion system facilitated the in vitro culture of a multiscale vascularized tissue under physiological pressure-, flow-, and oxygen-gradient conditions. With that, it presents a promising technique for the in vitro generation and culture of complex large-scale vascularized tissues.

In this study, we present the design, simulation, and implementation of a DC-DC synchronous buck converter utilizing IISB’s 2 μm 4H-silicon carbide (SiC) complementary metal–oxide–semiconductor (CMOS) technology. The converter is designed to meet the demands of modern integrated circuits, particularly in the field of integrated power management. The SiC technology offers enhanced performance and reliability at high temperatures, making it especially suitable for applications that operate in these conditions, including automotive systems, and aerospace, among others. The power transistors and gate drivers are fully integrated on-chip, optimizing efficiency and minimizing footprint. Additionally, the study contributes to the understanding of SiC technology and its application in integrated circuit design. Simulation results demonstrate a peak efficiency of 86.6% at 120 mA load current and 84.8% at 300 mA load current, showing the converter performance under different operating conditions. Furthermore, at high temperatures (295 °C), the converter achieves an efficiency of 89.6%, demonstrating its robustness and versatility in extreme environments. These findings contribute to the advancement of integrated circuit design and facilitate advancements in more efficient and robust power management solutions.

The intricate structure of human hands requires personalized orthotic treatments, especially with the growing aging population’s demand for accessible care. While traditional orthoses are effective, they face challenges of cost, customization time, and accessibility. Additive manufacturing, particularly material extrusion (MEX) techniques, can effectively address challenges in orthotic device production by enabling automated, complex, and cost-effective solutions. This work aims to provide engineers with a comprehensive set of design considerations for developing hand orthoses using MEX technology, focusing on applying design for additive manufacturing principles, to enhance rehabilitation outcomes. This objective is achieved by establishing design requirements for hand orthoses, reviewing design choices and methodologies across conventional and state-of-the-art MEX-based devices, and proposing an innovative approach to orthotic design. Hand orthosis design requirements were gathered through workshops with occupational therapists and categorized into engineer-, medical-, and patient-specific needs. A review of 3D-printed hand orthoses using MEX analyzes various design approaches, providing insights into existing solutions. The study introduces a modular design concept aimed at improving rehabilitation by enhancing customizability and functionality. It highlights the potential of MEX for creating personalized, cost-effective orthoses and offers recommendations for future research, to optimize designs and improve patient outcomes.

The potato is the most important non-cereal food crop, and thus improving potato growth and yield is the focus of agricultural researchers and practitioners worldwide. Several studies reported beneficial effects of silicon (Si) fertilization on potato performance, although plant species from the family Solanaceae are generally considered to be non-Si-accumulating. We used results from two field experiments in the temperate zone to gain insight into silica accumulation in potato plants, as well as corresponding long-term potato yield performance. We found relatively low Si contents in potato leaves and roots (up to 0.08% and 0.3% in the dry mass, respectively) and negligible Si contents in potato tuber skin and tuber flesh for plants grown in soils with different concentrations of plant-available Si (field experiment 1). Moreover, potato yield was not correlated to plant-available Si concentrations in soils in the long term (1965–2015, field experiment 2). Based on our results, we ascribe the beneficial effects of Si fertilization on potato growth and yield performance reported in previous studies mainly to antifungal/osmotic effects of foliar-applied Si fertilizers and to changes in physicochemical soil properties (e.g., enhanced phosphorus availability and water-holding capacity) caused by soil-applied Si fertilizers.

Background/Objectives: Despite current treatments extending the lifespan of Glioblastoma (GBM) patients, the average survival time is around 15–18 months, underscoring the fatality of GBM. This study aims to investigate the impact of sample heterogeneity on gene expression in GBM, identify key metabolic pathways and gene modules, and explore potential therapeutic targets. Methods: In this study, we analysed GBM transcriptome data derived from The Cancer Genome Atlas (TCGA) using genome-scale metabolic models (GEMs) and co-expression networks. We examine transcriptome data incorporating tumour purity scores (TPSs), allowing us to assess the impact of sample heterogeneity on gene expression profiles. We analysed the metabolic profile of GBM by generating condition-specific GEMs based on the TPS group. Results: Our findings revealed that over 90% of genes showing brain and glioma specificity in RNA expression demonstrate a high positive correlation, underscoring their expression is dominated by glioma cells. Conversely, negatively correlated genes are strongly associated with immune responses, indicating a complex interaction between glioma and immune pathways and non-tumorigenic cell dominance on gene expression. TPS-based metabolic profile analysis was supported by reporter metabolite analysis, highlighting several metabolic pathways, including arachidonic acid, kynurenine and NAD pathway. Through co-expression network analysis, we identified modules that significantly overlap with TPS-correlated genes. Notably, SOX11 and GSX1 are upregulated in High TPS, show a high correlation with TPS, and emerged as promising therapeutic targets. Additionally, NCAM1 exhibits a high centrality score within the co-expression module, which shows a positive correlation with TPS. Moreover, LILRB4, an immune-related gene expressed in the brain, showed a negative correlation and upregulated in Low TPS, highlighting the importance of modulating immune responses in the GBM mechanism. Conclusions: Our study uncovers sample heterogeneity’s impact on gene expression and the molecular mechanisms driving GBM, and it identifies potential therapeutic targets for developing effective treatments for GBM patients.

Phage therapy has been proposed as a therapeutic alternative to antibiotics for the treatment of chronic, biofilm-related P. aeruginosa infections. To gain a deeper insight into the complex biofilm–phage interactions, we investigated in the present study the effect of three successive exposures to lytic phages of biofilms formed by the reference strains PAO1 and PA14 as well as of two sequential clinical P. aeruginosa isolates from the sputum of a patient with cystic fibrosis (CF). The Calgary device was employed as a biofilm model and the efficacy of phage treatment was evaluated by measurements of the biomass stained with crystal violet (CV) and of the cell density of the biofilm bacterial population (CFU/mL) after each of the three phage exposures. The genetic alterations of P. aeruginosa isolates from biofilms exposed to phages were investigated by whole-genome sequencing. We show here that the anti-biofilm efficacy of the phage treatment decreased rapidly with repeated applications of lytic phages on P. aeruginosa strains with different genetic backgrounds. Although we observed the maintenance of a small subpopulation of sensitive cells after repeated phage treatments, a fast recruitment of mechanisms involved in the persistence of biofilms to the phage attack occurred, mainly by mutations causing alterations of the phage receptors. However, mutations causing phage-tolerant phenotypes such as alginate-hyperproducing mutants were also observed. In conclusion, a decreased anti-biofilm effect occurred after repeated exposure to lytic phages of P. aeruginosa biofilms due to the recruitment of different resistance and tolerance mechanisms.

TIN-X (Target Importance and Novelty eXplorer) is an interactive visualization tool for illuminating associations between diseases and potential drug targets and is publicly available at newdrugtargets.org. TIN-X uses natural language processing to identify disease and protein mentions within PubMed content using previously published tools for named entity recognition (NER) of gene/protein and disease names. Target data is obtained from the Target Central Resource Database (TCRD). Two important metrics, novelty and importance, are computed from this data and when plotted as log(importance) vs. log(novelty), aid the user in visually exploring the novelty of drug targets and their associated importance to diseases. TIN-X Version 3.0 has been significantly improved with an expanded dataset, modernized architecture including a REST API, and an improved user interface (UI). The dataset has been expanded to include not only PubMed publication titles and abstracts, but also full-text articles when available. This results in approximately 9-fold more target/disease associations compared to previous versions of TIN-X. Additionally, the TIN-X database containing this expanded dataset is now hosted in the cloud via Amazon RDS. Recent enhancements to the UI focuses on making it more intuitive for users to find diseases or drug targets of interest while providing a new, sortable table-view mode to accompany the existing plot-view mode. UI improvements also help the user browse the associated PubMed publications to explore and understand the basis of TIN-X’s predicted association between a specific disease and a target of interest. While implementing these upgrades, computational resources are balanced between the webserver and the user’s web browser to achieve adequate performance while accommodating the expanded dataset. Together, these advances aim to extend the duration that users can benefit from TIN-X while providing both an expanded dataset and new features that researchers can use to better illuminate understudied proteins.

Familial amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is due to mutations in one of several target genes, including SOD1. So far, clinical records, rodent studies, and in vitro models have yielded arguments for either a primary motor neuron disease, or a pleiotropic pathogenesis of ALS. While mouse models lack the human origin, in vitro models using human induced pluripotent stem cells (hiPSC) have been recently developed for addressing ALS pathogenesis. In spite of improvements regarding the generation of muscle cells from hiPSC, the degree of maturation of muscle cells resulting from these protocols has remained limited. To fill these shortcomings, we here present a new protocol for an enhanced myotube differentiation from hiPSC with the option of further maturation upon coculture with hiPSC-derived motor neurons. The described model is the first to yield a combination of key myogenic maturation features that are consistent sarcomeric organization in association with complex nAChR clusters in myotubes derived from control hiPSC. In this model, myotubes derived from hiPSC carrying the SOD1 D90A mutation had reduced expression of myogenic markers, lack of sarcomeres, morphologically different nAChR clusters, and an altered nAChR-dependent Ca2+ response compared to control myotubes. Notably, trophic support provided by control hiPSC-derived motor neurons reduced nAChR cluster differences between control and SOD1 D90A myotubes. In summary, a novel hiPSC-derived neuromuscular model yields evidence for both muscle-intrinsic and nerve-dependent aspects of neuromuscular dysfunction in SOD1-based ALS.

Cell polarity is crucial for gastric mucosal barrier integrity and mainly regulated by polarity-regulating kinase partitioning-defective 1b (Par1b). During infection, the carcinogen Helicobacter pylori hijacks Par1b via the bacterial oncoprotein CagA leading to loss of cell polarity, but the precise molecular mechanism is not fully clear. Here we discovered a novel function of the actin-binding protein cortactin in regulating Par1b, which forms a complex with cortactin and the tight junction protein zona occludens-1 (ZO-1). We found that serine phosphorylation at S405/418 and the SH3 domain of cortactin are important for its interaction with both Par1b and ZO-1. Cortactin knockout cells displayed disturbed Par1b cellular localization and exhibited morphological abnormalities that largely compromised transepithelial electrical resistance, epithelial cell polarity, and apical microvilli. H. pylori infection promoted cortactin/Par1b/ZO-1 abnormal interactions in the tight junctions in a CagA-dependent manner. Infection of human gastric organoid-derived mucosoids supported these observations. We therefore hypothesize that CagA disrupts gastric epithelial cell polarity by hijacking cortactin, and thus Par1b and ZO-1, suggesting a new signaling pathway for the development of gastric cancer by Helicobacter.

Animals are influenced by the season, yet we know little about the changes that occur in most species throughout the year. This is particularly true in tropical marine animals that experience relatively small annual temperature and daylight changes. Like many coral reef inhabitants, the crown-of-thorns starfish (COTS), well known as a notorious consumer of corals and destroyer of coral reefs, reproduces exclusively in the summer. By comparing gene expression in 7 somatic tissues procured from wild COTS sampled on the Great Barrier Reef, we identified more than 2,000 protein-coding genes that change significantly between summer and winter. COTS genes that appear to mediate conspecific communication, including both signalling factors released into the surrounding sea water and cell surface receptors, are up-regulated in external secretory and sensory tissues in the summer, often in a sex-specific manner. Sexually dimorphic gene expression appears to be underpinned by sex- and season-specific transcription factors (TFs) and gene regulatory programs. There are over 100 TFs that are seasonally expressed, 87% of which are significantly up-regulated in the summer. Six nuclear receptors are up-regulated in all tissues in the summer, suggesting that systemic seasonal changes are hormonally controlled, as in vertebrates. Unexpectedly, there is a suite of stress-related chaperone proteins and TFs, including HIFa, ATF3, C/EBP, CREB, and NF-κB, that are uniquely and widely co-expressed in gravid females. The up-regulation of these stress proteins in the summer suggests the demands of oogenesis in this highly fecund starfish affects protein stability and turnover in somatic cells. Together, these circannual changes in gene expression provide novel insights into seasonal changes in this coral reef pest and have the potential to identify vulnerabilities for targeted biocontrol.

Tens of millions of images from biological collections have become available online over the last two decades. In parallel, there has been a dramatic increase in the capabilities of image analysis technologies, especially those involving machine learning and computer vision. While image analysis has become mainstream in consumer applications, it is still used only on an artisanal basis in the biological collections community, largely because the image corpora are dispersed. Yet, there is massive untapped potential for novel applications and research if images of collection objects could be made accessible in a single corpus. In this paper, we make the case for infrastructure that could support image analysis of collection objects. We show that such infrastructure is entirely feasible and well worth investing in.

Abstract Background RNA editing has been described as promoting genetic heterogeneity, leading to the development of multiple disorders, including cancer. The cytosine deaminase APOBEC3B is implicated in tumor evolution through DNA mutation, but whether it also functions as an RNA editing enzyme has not been studied. Results Here, we engineer a novel doxycycline-inducible mouse model of human APOBEC3B-overexpression to understand the impact of this enzyme in tissue homeostasis and address a potential role in C-to-U RNA editing. Elevated and sustained levels of APOBEC3B lead to rapid alteration of cellular fitness, major organ dysfunction, and ultimately lethality in mice. Importantly, RNA-sequencing of mouse tissues expressing high levels of APOBEC3B identifies frequent UCC-to-UUC RNA editing events that are not evident in the corresponding genomic DNA. Conclusions This work identifies, for the first time, a new deaminase-dependent function for APOBEC3B in RNA editing and presents a preclinical tool to help understand the emerging role of APOBEC3B as a driver of carcinogenesis.

Background: Prediabetes is frequently underdiagnosed and undertreated, yet it poses significant cardiovascular risks. This study investigates the impact of prediabetes on short- and long-term survival outcomes in patients who experienced ST-elevation myocardial infarction (STEMI). Methods: In this retrospective, single-center cohort study, we evaluated 725 STEMI patients stratified into non-diabetic, prediabetic, and diabetic groups based on HbA1c levels at presentation. A Kaplan–Meier survival analysis was employed to compare long-term outcomes over a three-year follow-up period. Cardiovascular risk factors, including hypertension and dyslipidemia, were analyzed across the groups. The discriminatory power of HbA1c for predicting all-cause mortality was assessed using an Area Under the Receiver Operating Characteristic (AUROC) analysis. Results: Of the 725 patients, 407 (56.1%) were non-diabetic, 184 (25.4%) were prediabetic, and 134 (18.5%) were diabetic. Prediabetic patients exhibited significant additional cardiovascular risk factors, such as arterial hypertension (67.4%) and dyslipidemia (78.3%), with prevalence rates between those of non-diabetic and diabetic patients. The Kaplan–Meier analysis revealed that at a three-year follow-up, prediabetic patients faced a survival disadvantage, with a significant decrease in survival rates compared to non-diabetic patients (log-rank p = 0.016); their survival outcomes approached those of diabetic patients (p = 0.125). The AUROC analysis demonstrated that HbA1c was a significant predictor of short- and long-term mortality, with a cut-off value of 5.75% and an Area Under the Curve (AUC) of 0.580–0.617 (95% CI: 0.458–0.721), indicating a moderate ability to predict survival in patients with STEMI. Conclusions: Prediabetes significantly worsens survival outcomes following STEMI, nearly approaching the risk level of diabetes. Integrating rigorous cardiovascular risk management strategies for prediabetic individuals, including lifestyle interventions and potentially pharmacological treatments, could prevent the progression to diabetes and mitigate associated cardiovascular risks.

Salvinia auriculata Aublet is a floating aquatic plant, capable of absorbing the excess of nutrients and water contaminants and can be used in effluent treatment plants. The ability to survive in degraded areas may be related to the association with beneficial bacteria capable of promoting plant growth. However, little is known about the microbiota associated with this aquatic plant and its potential application to the aquatic environment. In this sense, this work aims to identify bacteria associated with S. auriculata that could be able to promote plant growth. Eighteen bacterial strains were identified by sequencing of the 16S rRNA gene, belonging to the genera Agrobacterium, Bacillus, Curtobacterium, Enterobacter, Pseudomonas, Siccibacter, and Stenotrophomonas. All isolates produced indole compounds, 12 fixed N2, and 16 solubilized phosphate. A new strain of Enterobacter (sp 3.1.3.0.X.18) was selected for inoculation into S. auriculata. For this purpose, 500 mL of nutrient solution and 1 g of the plant were used in the control and inoculated conditions. Enterobacter inoculation promoted a significant increase (p ≤ 0.05) in fresh plant biomass (17%) after 4 days of cultivation. In summary, the present study characterized 18 plant-growth-promoting bacteria isolated from S. auriculata with potential for biotechnological application, such as the production of bioinoculants or biomass resources, to protect or improve plant growth under conditions of stress.

This study aimed to evaluate the microbiological quality of coconut water sold from street carts equipped with cooling coils or refrigerated at bakeries in the Grande Vitória Region, Brazil. Additionally, it assessed the phenotypic and genotypic antimicrobial resistance profiles of isolated enterobacteria. The results indicated that coconut water sold at street carts had lower microbiological quality compared to refrigerated samples, as evidenced by significantly higher counts of mesophilic microorganisms. Using MALDI-TOF, the following opportunistic pathogens were identified: Citrobacter freundii, Enterobacter bugandensis, E. kobei, E. roggenkampii, Klebsiella pneumoniae, and Kluyvera ascorbata. Three isolates—E. bugandensis, K. pneumoniae, and K. ascorbata—were classified as multidrug-resistant (MDR). Widespread resistance to β-lactams and cephalosporins was detected, and some isolates were resistant to quinolones, nitrofurans, and phosphonic acids. The gene blaCTX-M-2 was detected in C. freundii, E. bugandensis, E. kobei, and K. ascorbata. However, genes blaNDM, blaKPC, blaCMY-1, and blaCMY-2 were not detected in any isolate. The findings underscore the need to enhance good manufacturing practices in this sector to control the spread of antimicrobial resistance (AMR). To our knowledge, this is the first study documenting the presence of potentially pathogenic enterobacteria in coconut water samples and their associated phenotypic and genotypic AMR profiles.

Migration, a multifaceted phenomenon, has a significant impact on health. Migrants perform similar movement patterns within their country of origin, in transit, and in the country of destination, thus making it difficult to monitor TB treatment throughout the journey. The objective was to compare the effectiveness of different treatment modalities in adherence to the short-term regimen for LTBI (3HP) among international migrants and refugees. This is a quasi-experimental study conducted in Manaus-AM. The study population was made up of international migrants. The certification and monitoring of medication intake employed three strategies: self-administration (SA), directly observed conventional therapy (DOT), and Video Telemonitoring System for Tuberculosis Treatment (VDOT). The VDOT group and SA group exhibited the lowest rate of treatment dropout or interruption at 16.1%, followed by the DOT group at 23.1%. The results suggest that the most effective strategy for ensuring adherence among migrants and refugees was VDOT (OR_adj 0.26; CI 0.7–0.94), suggesting that migrants may be more likely to adhere to and complete their treatment. The results show that relying on different treatment strategies, adapted to the individuals’ needs and risk factors, is a viable and effective way of providing person-centered TB care.

Effects of pre- and probiotics on intestinal health are well researched and microbiome-targeting solutions are commercially available. Even though a trend to appreciate the presence of certain microbes on the skin is seeing an increase in momentum, our understanding is limited as to whether the utilization of skin-resident microbes for beneficial effects holds the same potential as the targeted manipulation of the gut microflora. Here, we present a selection of molecular mechanisms of cross-communication between human skin and the skin microbial community and the impact of these interactions on the host’s cutaneous health with implications for the development of skin cosmetic and therapeutic solutions. Malassezia yeasts, as the main fungal representatives of the skin microfloral community, interact with the human host skin via lipid mediators, of which several are characterized by exhibiting potent anti-inflammatory activities. This review therefore puts a spotlight on Malassezia and provides a comprehensive overview of the current state of knowledge about these fungal-derived lipid mediators and their capability to reduce aesthetical and sensory burdens, such as redness and itching, commonly associated with inflammatory skin conditions. Finally, several examples of current skin microbiome-based interventions for cosmetic solutions are discussed, and models are presented for the use of skin-resident microbes as endogenous bio-manufacturing platforms for the in situ supplementation of the skin with beneficial metabolites.

Urban sprawl leads to the degradation of aquatic environments and, consequently, to the destruction of biodiversity. With the aim of highlighting the distribution profile of benthic macroinvertebrates in the city of Yaoundé and its surroundings according to the level of degradation, this study was carried out in seven rivers. A total of 144 taxa of benthic macroinvertebrates, belonging to 74 families, 15 orders, five classes, and three phyla, were collected from seven rivers in urban, peri-urban, and forest environments on Yaoundé and its surroundings. The self-organizing map (SOM) analysis tool was used to group the collected taxa from all stations into three clusters or affinity cores. The indicator value analysis (IndVal) method was employed to determine, based on their ecological preferences, which organisms were most likely to belong to each group. Out of the 144 collected taxa, only 44 were indicated to represent the three different groups. Thus, three communities were defined: the Hydropsyche community, with Hydropsyche sp. as the predominant taxon in Group III, characterizing well-oxygenated and low-mineralized stations; the Hydrocyrius community, where the species Hydrocyrius sp. predominates in Group I, describing stations with low oxygenation and moderate mineralization; and the Lumbriculidae community, where Lumbriculidae is the taxon associated with environments with high mineralization and critical oxygenation. These two methods contribute to the biomonitoring of tropical aquatic environments, firstly by grouping organisms by affinity and then identifying those that reflect the environment conditions. This facilitates the detection of changes in the quality of hydrosystems and guides management and conservation efforts.

Abstract Background Liquid biopsy is a minimally-invasive method of sampling bodily fluids, capable of revealing evidence of cancer. The distribution of cell-free DNA (cfDNA) fragment lengths has been shown to differ between healthy subjects and cancer patients, whereby the distributional shift correlates with the sample’s tumour content. These fragmentomic data have not yet been utilised to directly quantify the proportion of tumour-derived cfDNA in a liquid biopsy. Results We used statistical learning to predict tumour content from Fourier and wavelet transforms of cfDNA length distributions in samples from 118 cancer patients. The model was validated on an independent dilution series of patient plasma. Conclusions This proof of concept suggests that our fragmentomic methodology could be useful for predicting tumour content in liquid biopsies.

Abstract Background Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. Main Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects (“SNP-to-gene” mapping), (ii) genes with kidney phenotypes in mice or human (“gene-to-phenotype”), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function (“GPS tab”) to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data ( https://kidneygps.ur.de/gps/ ). Conclusion With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo research.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.

Predicting the interaction between Major Histocompatibility Complex (MHC) class I-presented peptides and T-cell receptors (TCR) holds significant implications for vaccine development, cancer treatment, and autoimmune disease therapies. However, limited paired-chain TCR data, skewed towards well-studied epitopes, hampers the development of pan-specific machine-learning (ML) models. Leveraging a larger peptide-TCR dataset, we explore various alterations to the ML architectures and training strategies to address data imbalance. This leads to an overall improved performance, particularly for peptides with scant TCR data. However, challenges persist for unseen peptides, especially those distant from training examples. We demonstrate that such ML models can be used to detect potential outliers, which when removed from training, leads to augmented performance. Integrating pan-specific and peptide-specific models alongside with similarity-based predictions, further improves the overall performance, especially when a low false positive rate is desirable. In the context of the IMMREP22 benchmark, this modeling framework attained state-of-the-art performance. Moreover, combining these strategies results in acceptable predictive accuracy for peptides characterized with as little as 15 positive TCRs. This observation places great promise on rapidly expanding the peptide covering of the current models for predicting TCR specificity. The NetTCR 2.2 model incorporating these advances is available on GitHub (https://github.com/mnielLab/NetTCR-2.2) and as a web server at https://services.healthtech.dtu.dk/services/NetTCR-2.2/.

The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as it requires the decoupling of the mechanisms supporting progenitor self-renewal and expansion from those mechanisms promoting their differentiation. This study focuses on the expansion of human pluripotent stem (hPS) cell-derived pancreatic progenitors (PP) to advance novel therapies for diabetes. We obtained mechanistic insights into PP expansion requirements and identified conditions for the robust and unlimited expansion of hPS cell-derived PP cells under GMP-compliant conditions through a hypothesis-driven iterative approach. We show that the combined stimulation of specific mitogenic pathways, suppression of retinoic acid signaling, and inhibition of selected branches of the TGFβ and Wnt signaling pathways are necessary for the effective decoupling of PP proliferation from differentiation. This enabled the reproducible, 2000-fold, over 10 passages and 40–45 d, expansion of PDX1+/SOX9+/NKX6-1+ PP cells. Transcriptome analyses confirmed the stabilization of PP identity and the effective suppression of differentiation. Using these conditions, PDX1+/SOX9+/NKX6-1+ PP cells, derived from different, both XY and XX, hPS cell lines, were enriched to nearly 90% homogeneity and expanded with very similar kinetics and efficiency. Furthermore, non-expanded and expanded PP cells, from different hPS cell lines, were differentiated in microwells into homogeneous islet-like clusters (SC-islets) with very similar efficiency. These clusters contained abundant β-cells of comparable functionality as assessed by glucose-stimulated insulin secretion assays. These findings established the signaling requirements to decouple PP proliferation from differentiation and allowed the consistent expansion of hPS cell-derived PP cells. They will enable the establishment of large banks of GMP-produced PP cells derived from diverse hPS cell lines. This approach will streamline SC-islet production for further development of the differentiation process, diabetes research, personalized medicine, and cell therapies.

The pervasive presence of plastic in the environment has reached a concerning scale, being identified in many ecosystems. Bioremediation is the cheapest and most eco-friendly alternative to remove this polymer from affected areas. Recent work described that a novel cold-active esterase enzyme extracted from the bacteria Kaistella jeonii could promiscuously degrade PET. Compared to the well-known PETase from Ideonella sakaiensis, this novel esterase presents a low sequence identity yet has a remarkably similar folding. However, enzymatic assays demonstrated a lower catalytic efficiency. In this work, we employed a strict computational approach to investigate the binding mechanism between the esterase and PET. Understanding the underlying mechanism of binding can shed light on the evolutive mechanism of how enzymes have been evolving to degrade these artificial molecules and help develop rational engineering approaches to improve PETase-like enzymes. Our results indicate that this esterase misses a disulfide bridge, keeping the catalytic residues closer and possibly influencing its catalytic efficiency. Moreover, we describe the structural response to the interaction between enzyme and PET, indicating local and global effects. Our results aid in deepening the knowledge behind the mechanism of biological catalysis of PET degradation and as a base for the engineering of novel PETases.

Understanding habitat extension that limits species distribution is a crucial tool for management and conservation, in which habitat mapping plays a pivotal role. The mesovoid shallow substratum (MSS) is a type of shallow subterranean habitat with an important conservation value for invertebrate communities, functioning as climatic/reproductive refuge, biogeographic corridor and/or permanent habitat. Methodologies to map the mesovoid shallow substratum (MSS) are currently lacking. We propose a novel method for colluvial MSS habitat mapping, combining geographic information systems, geological maps, and geological knowledge on the habitat genesis. We tested and validated the efficiency of the method using the Arrábida karst area (Portugal) as a model. The method allowed the remote detection of MSS habitats suitable for invertebrate communities ex situ within the study area, and enabled the estimation of habitat extent. The faunal communities sampled in the selected location were dominated by arthropods, especially insects, showcasing the efficacy of this mapping method to detect suitable MSS habitats. The use of this method considerably reduces the in situ scouting area, providing a more efficient way of locating these habitats. The MSS is protected under EU legislation concerning floral communities and geological features, completely neglecting its faunal communities. This method also allows to estimate potential MSS habitat extension in several lithologies, facilitating the implementation of invertebrate prospections, and the establishment of more effective conservation measures.

Haemotrophic mycoplasmas (haemoplasmas) are a group of highly specific and adapted bacteria. Three different haemoplasma species in pigs are known to date: Mycoplasma (M.) suis, M. parvum and ‘Candidatus (Ca.) M. haemosuis’. Even though these bacteria have been known in pig farming for a long time, it is difficult to draw general conclusions about the relevance of their infections in pigs. This review summarizes the current knowledge on the three porcine haemoplasma species with regards to clinical and pathological descriptions, pathobiology, epidemiology and diagnostics as well as prevention and therapy. Overall, it is clear that considerably more data are available for M. suis than for the other two species, but generally, porcine haemoplasmas were found to be highly prevalent all over the world. Mycoplasma suis is the most virulent species, causing acute infectious anaemia in pigs (IAP), whereas M. parvum usually results in chronic and subclinical infections associated with performance losses. Little is known about the clinical significance of the recently discovered third porcine species ‘Ca. M. haemosuis’. So far, the described pathogenic mechanisms mainly include direct destruction of erythrocytes via adhesion, invasion, eryptosis and nutrient scavenging, indirect erythrocyte lysis due to immune-mediated events and immune dysregulation processes. A review of published diagnostic data confirms PCR assays as the current standard method, with various cross-species and species-specific protocols. Overall, there is a need for further examination to obtain valuable insights for practical application, specifically regarding the importance of subclinical infections in naturally infected animals. An essential requirement for this will be to gain a more comprehensive understanding of the mechanisms operating between the host and the pathogen.

Hemotrophic mycoplasmas (HMs) are highly host-adapted and specialized pathogens infecting a wide range of mammals including farm animals, i.e., pigs, cattle, sheep, and goats. Although HMs have been known for over 90 years, we still do not know much about the natural transmission routes within herds. Recently, it has been repeatedly discussed in publications that arthropod vectors may play a role in the transmission of HMs from animal to animal. This is mainly since several HM species could be detected in different potential arthropod vectors by PCR. This review summarizes the available literature about the transmission of bovine, porcine, ovine, and caprine HM species by different hematophagous arthropod vectors. Since most studies are only based on the detection of HMs in potential vectors, there are rare data about the actual vector competence of arthropods. Furthermore, there is a need for additional studies to investigate, whether there are biological vectors in which HMs can multiply and be delivered to new hosts.

This study explores social-psychological barriers that may affect resilience in the context of sustainability. These barriers can be understood as unobserved processes that reduce the capacity of a social-ecological system to recover after a perturbation or transformation. Analyzing social-psychological processes enables us to distinguish passive and active processes, at the individual and collective levels. Our work suggests that interacting social and psychological processes should be considered as dynamically evolving determinants of resilience, especially when perturbations can change the psychology of individuals, and thus the underlying dynamics of social-ecological systems. Hence, considering social-psychological barriers and the conditions under which they emerge may provide decision makers with useful insights for coping with ineluctable uncertainties that reduce systems’ transformative capacity and thus their general resilience.

A high-performance liquid chromatography method coupled to tandem mass spectrometry was validated in order to study the pharmacokinetics of cefotaxime in shrimp hepatopancreases and plasma, as well as its withdrawal time related to a maximum residue limit (MRL) in shrimp muscle. Pharmacokinetics parameters were investigated through oral medication at a single dose of 25 mg/kg shrimp body weight and subsequent hepatopancreas and plasma cefotaxime concentration measurements at 0.5, 1, 2, 4, 8, 12 and 24 h after shrimp were fed with medication. The maximum concentration of cefotaxime was observed after one hour in the hepatopancreas (Cmax, 19.45 ± 2.10 mg/kg) and 4 h in plasma (0.184 ± 0.061 mg/L). Based on a minimum inhibitory concentration (MIC) of cefotaxime of 4.13 mg/L against Vibrio parahaemolyticus (known to cause acute hepatopancreatic necrosis disease (AHPND) in white leg shrimp), it was observed that the time during which the hepatopancreas cefotaxime concentration was above the MIC was 23 h. An every 24 h cefotaxime treatment could thus be effective in fighting against this bacterium in shrimp. The withdrawal time of cefotaxime was determined after shrimp were fed with medicated feed once a day and twice a day for three consecutive days. Shrimp muscle was collected on day 1 and day 3 during medication and 1, 3, 7, 14 and 21 days after medication was stopped. Considering an MRL of 50 μg/kg, the withdrawal times were 8.5 degree-days (corresponding to 6.9 h at 29.5 °C) after shrimp were fed with medicated feed once a day for 3 days and 95.5 degree-days (77.7 h at 29.5 °C) after shrimp were fed with medicated feed twice a day for 3 days. Moreover, histological analysis revealed that feeding shrimp with cefotaxime at the given dose in once- or twice-a-day treatments did not negatively impact the shrimp hepatopancreas.

Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate. Methods: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations. Findings: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals. Interpretation: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.

Prosopis juliflora is a shrub/tree originating from the Americas. Since its introduction for fuel wood afforestation into eastern Africa, it has been invading crop- and rangelands with negative effects on the environment and on livelihoods. Understanding the management strategies for Prosopis and matching them with ecological, social-cultural, and economic needs of the eastern African region is a pressing scientific issue. We analyzed management strategies of Prosopis, focusing on determinants and drivers of their choice of applied management strategies as well as their effectiveness. We identified 1917 scientific contributions published between 1970 and 2022. Following a multi-step screening, we reduced the references to 53 relevant (internationally) published papers with a focus on the management of Prosopis in the east African region. Analysis of the literature shows that factors driving invasion dynamics but also land users’ social-economic as well as cultural attributes determine the type of management strategy and shape local control actions. Main strategies comprise (1) physical containment of invasive spread, (2) chemical, mechanical and biological approaches to reduce stand densities, (3) complete eradication, (4) restoration of invaded land, and (5) economic use of Prosopis products. Adopted strategies are based on actual and perceived impacts of invasion, and the adoption and success of individual strategies is highly location specific.