Quinone outside inhibitor (QoI) fungicide resistance in A. alternata populations was reported in Brazil for the first time in 2019, in São Paulo orchards, and the mutation G143A in cytochrome b ( cytb) was found in resistant isolates. Our study investigated the infectious process, production of Reactive Oxygen Species (ROS) and fungal cell death in resistant (QoI-R) and sensitive (QoI-S) Alternaria alternata pathotype tangerine (Aapt) isolates. Morphological characterization of Aapt isolates was performed using Confocal Laser Scanning Microscopy (CLSM). Alternaria brown spot (ABS) symptoms were produced by Aapt isolates on tangelo cv. BRS Piemonte. Germination of QoI-R conidia and production of germ tubes on tangelo leaflets treated with 100µg mL -1 of pyraclostrobin 18 hours after inoculation (hai) was observed using Scanning Electron Microscopy (SEM). At the same time, QoI-S conidial germination was inhibited on tangelo leaflets treated with pyraclostrobin. ROS production and cell death in Aapt isolates at high fungicide concentration were observed using CLSM. QoI-S conidia exhibited high ROS production, indicating high oxidative stress. When dyed with Propidium Iodate (PI), QoI-S conidia emitted red fluorescence, showing cell death and confirming their sensitive phenotype. In contrast, QoI-R conidia neither produced ROS nor exhibited red fluorescence, indicating no cell death and confirming their resistant phenotype. Therefore, our findings evidence that microscopic techniques may help characterize events during fungi-plant interactions, ROS production, cell death, and Aapt phenotypes resistant and sensitive to QoIs using fluorometric protocols. Research Highlights Our findings demonstrate the infection process, reactive oxygen species production, and cell death of Aapt isolates resistant and sensitive to quinone outside inhibitors (QoIs). Confocal laser scanning microscopy may help to characterize phenotypes resistant and sensitive to QoIs using fluorometric protocols.

Abstract Background IL4 is a versatile cytokine essentially known for differentiation, proliferation, and cell death in cells. Its dysregulation has been found to be associated with the development of inflammatory disorders. Objective The goal of the current investigation is to identify and select non-synonymous single nucleotide polymorphisms (nsSNPs) in the IL-4 gene by employing computational methods which may have a potential functional impact on the occurrence of disease. Method & Result Six different nsSNPs were predicted to be deleterious based on the consensus of different algorithms: SIFT, Polyphen2 (Humdiv and HumVar), PredictSNP, and SNP&GO.I-mutant and MuPro assessment revealed a decrease in the stability of these mutants except K150M. Modelling was then carried out to build the wild-type along with its mutants, followed by superimposition of the wild-type with mutants to evaluate the RMSD value, which lies between 0.26-0.34. Simulation results of mutant models, along with wild-type, showed that four of the mutants (N113Y, A118G, R109W, and K150M) deviated most and were unstable. A118G showed a significant deviation from the wild-type, while V53A and C123R were stable. Conclusion The finding establishes the evidence that the identified six nsSNPs of IL-4 can be the new entrant presenting their candidature for genetic testing.

Global climate change is causing extreme heating events and intensifying infectious disease outbreaks. We tested whether warming (at various host life stages) could shape the ecological and evolutionary trajectory of host resistance, by competing nematode host genotypes across 10 generations during infection by a natural bacterial pathogen. We found that persistent warming throughout host development and during infection strongly favoured genetic-based host resistance. Ambient temperatures or periodic warming within host lifetime resulted in the loss of genetic-based resistance, despite pathogen presence. Warming during host development caused plastic temperature-mediated protection which weakened selection for more costly resistance. The findings of an associated mechanistic model suggest that dilution of pathogen cells by resistant hosts might help protect susceptible individuals when warming does not occur during development. Host evolutionary trajectories were likely driven by the combination of fitness constraints on genetic-based resistance, host plasticity, condition-dependent pathogen virulence, and dilution effects.

Species diversity of consumers is known to promote high attack rates when species differ in their traits and the resources they use. Yet, despite considerable work on the role of species diversity, we lack information on how genetic diversity at different trophic levels affects rates of ecosystem processes such as trophic interactions. Here, we assess whether the available genetic diversity in three trophic levels influences parasitism rates, both within and across generations. We used experimental population bottlenecks to create a gradient of decreasing genetic diversity of hosts and parasitoids, and measured rates of parasitism, host resistance to parasitism, and host survival over 11 host generations. Less-inbred parasitoid populations exerted higher parasitism rates (analogous to known effects of species diversity), however, this effect became weaker over time. We conclude that genetic diversity can have short-term ecological impacts in trophic systems, which can be altered in the long term by evolutionary processes.

This paper presents a collaborative control strategy for landing the nose of an aircraft on a mobile target platform, addressing the issue of total landing gear malfunction during the landing phase. The strategy guides the aircraft along a desired trajectory while controlling the target platform’s speed to ensure simultaneous arrival at the designated position. The system model comprises the kinematic model of a Boeing 747 and a ground platform. A nonlinear aircraft controller, based on the sliding mode control technique, is designed for autonomous landing maneuvers. System stability is ensured using Lyapunov stability theory. The proposed controller’s effectiveness is demonstrated through numerical simulations and compared with the conventional proportional-integral controller, validating its superior performance.

Landscape heterogeneity is known as a major factor of community structure and composition. Whether this effect of the landscape extends at different scales and particularly at the relevant scale for microorganisms remained to be determined. We used the cases produced by aquatic larvae of Trichoptera, which assemble organic or mineral particles, as naturally replicated experimental systems to determine the effect of landscape structuration on microbial communities. A metabarcoding approach was used to characterise fungal, bacterial and diatom communities on cases produced by six Trichoptera species and related unstructured organic and mineral substrates. The structuration of the particles constituting the cases was also determined as a measure of microscale landscape. Trichoptera cases harboured communities of diatoms, fungi and bacteria that differed from those found on unstructured substrates. Microbial communities also differed between organic and mineral substrates. We found a higher microbial diversity on cases than on unstructured substrates. The heterogeneity of the microscale landscape also affected bacterial and fungal communities within cases. These results highlight the importance of microscale landscape structuration for microbial diversity and demonstrate that approaches of landscape ecology could be downscaled to the microscale.

The effective prioritization of drug resistance mutations affecting protein folding and interactions is crucial for treatment success. To address this, a bioinformatics pipeline, AMIA, is introduced, integrating various structural analysis tools into a simplified workflow. By optimizing computational resources, data transformations are automated, enhancing scalability and reproducibility. AMIA automates mutation introduction into protein structures, calculates polar interaction changes, and analyses protein fold energy through pre-established software tools. Furthermore, it includes automated molecular dynamics analysis, reducing the need for constant user input and output management. This open-source pipeline facilitates the visualization of mutation effects on protein structure and dynamic states, aiding in prioritizing variants for experimental validation. AMIA (available at: https://github.com/kbrown3687524/amia) streamlines computational analysis, contributing to improved treatment regimen development against drug-resistant mutations.

Climate change poses threats to biodiversity, particularly in tropical rainforests. How tropical rainforest tree species will respond to climate change is uncertain because their extent of local adaptation, its drivers and genetic basis remain poorly known. Characterizing these and the risks of maladaptation in future climates can inform on possible responses and help design strategies for the conservation. This study focuses on Dicorynia guianensis (Fabaceae), a widespread tree species in French Guiana, known for its sensitivity to drought. We performed genome resequencing on 87 individuals sampled in 11 sites across French Guiana to investigate the genetic structure, diversity, the drivers and the genetic basis of local adaptation. Genetic structure analysis identified three distinct groups: western, inland, and eastern, with similar levels of genetic diversity and distributed in areas with different environmental conditions. Six methods applied to detect genomic signatures of selection revealed region-specific selective sweeps and overlap between SNPs identified through outlier analysis or genome-environment association analyses. The most relevant environmental drivers of selection were potential evapotranspiration of the wettest quarter and precipitation of the coldest quarter, indicating that environmental variables related to high rainfall during the wet season are stronger drivers of local adaptation of D. guianensis than drought. Sites located in inland French Guiana had higher risks of climatic maladaptation than coastal sites. Our results contribute to the understanding of local adaptation and risk of maladaptation in tropical trees. They emphasize the need for area-specific approaches in managing tropical tree under the pressures of climate change.

Demographic processes can substantially affect a species’ response to changing ecological conditions, necessitating the combined consideration of genetic responses to environmental variables and neutral genetic variation. Using a seascape genomics approach combined with population demographic modelling, we explored the interplay of demographic and environmental factors that shaped the current population structure in Indo-Pacific bottlenose dolphins (Tursiops aduncus) along most of the western Australian coastline. We combined large-scale environmental data gathered via remote sensing with RADseq genomic data from 138 individuals at 19 sampling sites. Using population genetic and outlier detection anaylses, we identified three distinct genetic clusters, coinciding with tropical, subtropical and temperate provincial bioregions. In contrast to previous studies, our demographic models indicated that populations occupying the paleo-shoreline split into two demographically independent lineages before the last glacial maximum (LGM). A subsequent split after the LGM at 8.5 kya gave rise to the Shark Bay population, thereby creating the three currently observed clusters. Although multi-locus heterozygosity declined from north to south, dolphins from the southernmost cluster inhabiting temperate waters had higher heterozygosity in potentially adaptive loci, compared to dolphins from subtropical and tropical waters. These findings suggest ongoing adaptation to cold temperate waters in the southernmost cluster, possibly linked to distinct selective pressures between the different bioregions. Our study demonstrated that in the marine realm, without apparent physical boundaries, only a combined approach can fully elucidate the intricate environmental and genetic interactions shaping the evolutionary trajectory of marine mammals.

Goals: The intranasal Schirmer test (INS) is a quick method to objectify nasal secretion. This study aims to use the INS to assess nasal secretion change through direct nasal allergen provocation (NPT). Material and Methods: This prospective single-center study included patients who received allergy diagnostics using NPT and anterior rhinomanometry (aRMM). The Schirmer filter paper was attached to the nasal septum bilaterally pre- and post-allergen provocation. Additionally, all participants completed the sinonasal outcome test 22 (SNOT-22). The difference in wetting length before and after allergen provocation was investigated. Moreover, a cut-off value for allergic rhinitis were calculated. Results: A total of n = 25 patients and n = 25 in the control group were included. Patients with a positive result in NPT showed a significantly higher secretion in the provoked nasal cavity (mean difference = 13.95 mm; p = 0.01). The increased moisture level through provocation resulted in an area under the curve (AUC) of 0.814. A cut-off value of 2.75 mm wetting length increase (Youden index = 0.532) was calculated (sensitivity = 81.8% and specificity = 71.4%). Allergy diagnostic patients scored significantly higher in the SNOT-22 than the control group (25.04 score difference; p < 0.001). Conclusion: The INS represents a straightforward and cost-effective test to assess intranasal secretion changes in allergy diagnostics. The incorporation of the INS in the NPT protocol could particularly enhance treatment efficacy for patients with inconclusive NPT results or it could serve as a substitute for other objective measurements like aRMM or acoustic rhinometry.

The deployment of large language models (LLMs) on edge devices and non-server environments presents significant challenges, primarily due to constraints in memory usage, computational power, and inference time. This paper investigates the feasibility of running LLMs across such devices by focusing on optimizing memory usage, employing quantization techniques, and reducing inference time. Specifically, we utilize LLaMA 2 for biomedical text summarization and implement Low-Rank Adaptation (LoRA) quantization to compress the model size to compress the model size and fine-tune it using limited resources. Our study systematically evaluates memory consumption during both training and inference phases, demonstrating substantial reductions through efficient LoRA quantization. Our results indicate that with careful optimization, it is feasible to deploy sophisticated LLMs like LLaMA 2 on low powered devices, thereby broadening the scope of their application in resource-constrained environments.

Fluctuations in genomic repetitive fractions (repeatome) are known to impact several facets of evolution, such as ecological adaptation and speciation processes. Therefore, investigating the divergence of repetitive elements can provide insights into an important evolutionary force. However, it is not clear how the different repetitive element lineages are impacted by the ecological changes. To discuss this, we used the Neotropical legume genus Erythrostemon (Caesalpinioideae) as a model, given its ancient origin (~33 Mya), lineage-specific niche conservatism, macroecological heterogeneity, and disjunct distribution in Meso- and South American (MA and SA, respectively) lineages. We performed a comparative repeatomic analysis of 18 Erythrostemon species to test the impact of environmental variables over repeats diversification. Overall, repeatome composition was diverse, with high abundances of satDNAs and Ty3/gypsy-Tekay transposable elements, predominantly in the MA and SA lineages, respectively. Remarkably the first divergent lineages (E. pannosus and E. placidus) of the MA clade preserve plesiomorphic Tekay and satDNA patterns. This pattern was altered in the MA-sensu stricto subclade with a striking genomic differentiation (expansion of satDNA and retraction of Tekay) associated with the colonization of a new environment in Central America around 20 Mya. Our data reveal that the current species-specific Tekay pool was the result of two bursts of amplification probably in the Miocene, with distinct patterns for the MA and SA repeatomes. This suggests a strong role of the Tekay elements as modulators of the genome-environment interaction in Erythrostemon, providing macroevolutionary insights about mechanisms of repeatome differentiation and plant diversification across space and time.

Various test structures can be used to determine the specific contact resistivity of ohmic contacts. The transmission line model test structure and circular transmission line model test structure are the most commonly used. The analytical expressions of the former are straightforward and effectively describe the electrical behavior of a contact, while the concentric geometry of the latter eliminates complications during fabrication. In this paper, we present a hybrid test structure that combines the advantages of the transmission line and the circular transmission line models. The analytical expressions of the new structure are presented, and its finite-element modeling is undertaken. The effect of contact geometry on this test structure is also discussed. Using the presented test structure, determining contact parameters does not require any error corrections.

With organizations seeking faster, cheaper, and smarter ways of delivering higher quality software, many are looking towards generative artificial intelligence (AI) to drive efficiencies and innovation throughout the software development lifecycle. However, generative AI can suffer from several fundamental issues, including a lack of traceability in concept generation and decision making, the potential for making incorrect inferences (hallucinations), shortcomings in response quality, and bias. Quality engineering (QE) has long been utilized to enable more efficient and effective delivery of higher quality software. A core aspect of QE is adopting quality models to support various lifecycle practices, including requirements definition, quality risk assessments and testing. In this position paper, we introduce the application of QE to AI systems, consider shortcomings in existing AI quality models from the International Organization for Standardization (ISO), and propose extensions to ISO models based on the results of a survey. We also reflect on skills that IT graduates may need in the future, to support delivery of better-quality AI.

Ecosystem services (ESs) are an important bridge coupling the natural environment and human society. The Qinghai-Tibetan Plateau (QTP), as an ecological barrier in China and even in Asia, plays a key role in maintaining regional ecological security and sustainable supply of water resources. However, there is limited research on determining thresholds and zoning for the effects of fractional vegetation cover (FVC) on ESs over long periods of time. This study took the QTP as the study region, analyzed the long-term changes and short-term fluctuations of key ESs, determined the impact thresholds of FVC, and designated the ecological functional areas of the QTP and different land types. The results showed that all key ESs increased of different degrees from 2000 to 2022. The mean values of the Interannual Fluctuation Index (IFI) for Water Yield (WY), Habitat Quality (HQ), Carbon Storge (CS), Soil Conservation (SC), Climate Regulation (CR) and Food Supply (FS) were 13.08%, 5.66%, 36.01%, 8.31%, 22.77% and 51.69%, respectively. The impact thresholds of FVC on Total Ecosystem Services (TES) in the QTP, grassland, forest and barren were 0.44, 0.40, 0.29 and 0.23, respectively. Based on the threshold analyzed, the Ecological Safety Area (ESA), Ecological Transition Area (ETA) and Ecological Protection Area (EPA) were delineate, which provided theoretical support for the ecological restoration and sustainable development of the QTP.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a standard treatment for advanced Parkinson’s disease (PD). The precise positioning of the electrode can significantly influence the results of DBS and the overall improvement in the quality of life for PD patients receiving this therapy. We hypothesize that single unit activity (SUA) features can serve as a valid marker of the optimal DBS-electrode insertion trajectory, leading to the most favorable outcome of STN-DBS surgery. We analyzed spontaneous SUA data recorded during Microelectrode Recording (MER) for 21 patients with PD who underwent DBS surgery. We compared 29 linear and 6 nonlinear characteristics of the STN neural activity recorded along different microelectrode insertion paths to determine features corresponding to favorable stimulation outcomes. Our research indicated that the SUA features of pause neurons in a dorsal STN region significantly affected stimulation outcomes. For the trajectories chosen for lead insertion, firing rate, burst rate, and oscillatory activity at 8-12 and 12-20 bands were significantly decreased. Moreover, nonlinear feature analysis showed a significant increase in mutual information for the chosen trajectories. Our findings highlight the significance of specific indicators, such as the activity of pause neurons in the dorsal region and numerous linear SUA characteristics, in determining the optimal lead installation trajectory. Furthermore, our findings emphasize the importance of investigating paths rejected during test-stimulation to understand motor impairment in Parkinson’s disease and its treatment mechanisms.

Yohimbine is a new erectile dysfunction compound derived from natural products, and its pharmacokinetic study is of great significance for its further development as a new drug.In this work, we developed a novel ZIF-8-based solid phase microextraction SPME-LC-MS/MS(Solidphasemicro extraction-liquid chromatography-mass spectrometry/mass spectrometry)method for the analysis of yohimbine in plasma and further for pharmacokinetic studies.The synthetic ZIF-8(zeolitic imidazolate frameworks-8) was used as the adsorbent for yohimbine microextraction, and the parameters affecting the extraction efficiency were systematically studied. Under optimal conditions, the SPME method based on pipette gun head showed excellent enrichment efficiency for yohimbine.A SPME -LC-MS/MS method for the determination of yohimbine in plasma samples was established. The linear range of the method is wide (0.3125-250ng/mL), and the R is 0.99063. By LC-MS/MS detection, the detection limit was as low as 0.104 ng/mL. Finally, the pharmacokinetics of Yohimbine were studied and compared with existing methods.

Food security depends on the early detection of agricultural diseases, particularly in Sub-Saharan Africa. Professionals visually evaluate the plants by searching for disease indications on the leaves to diagnose cassava infections, a notoriously subjective process. Farmers in remote areas may be able to monitor their crops without the assistance of specialists if crop diseases are automatically detected and classified. This could aid in the more accurate diagnosis of diseases by professionals. Crop disease classification and early identification have benefited from the application of machine learning techniques. Despite their excellent accuracy, there is no single machine learning model that can provide optimal results on all the datasets. In this study, a Bayesian optimization of the Convolutional Neural Network (CNN) model was proposed. The model was trained using the spectral dataset. Since spectral data is highly dimensional, dimensionality reduction was performed on the dataset using PCA. The experimental results revealed that the proposed model had an accuracy of 85.19%, Precision of 85.23%, Recall of 85.16%, and F1 score of 85.20%. Also, the proposed model had an AUC of 0.95 which demonstrates excellent performance. However, there is still a need to improve the overall performance of the proposed model and we recommend the use of a pretrained transfer learning approach in future studies.

Chlorhexidine gluconate (CHG) is a topical antiseptic and surgical scrub increasingly implicated in periprocedural anaphylaxis. We present four patients who had anaphylaxis in the setting of CHG exposure, an agent that has been increasingly implicated in periprocedural anaphylaxis. Catheters can be impregnated with CHG and overlooked as a source of exposure resulting in anaphylaxis.

The prescription of medications should be a constant concern in the daily practice of doctors, focusing not only on potential interactions with other prescription drugs, but also with herbal medicines, natural remedies, substances of misuse, and even certain foods. Minimizing the risks of interactions between these substances is the duty of all doctors.

Background: Leukoreduction by filtration (LRF) is a common procedure in human blood banks, and has also been used to reduce the transmission of infectious agents such as viruses, bacteria, and blood parasites. Objective: This study aimed to evaluate the efficiency of filtration leukoreduction in the quantitative control of Escherichia coli inoculated into equine blood bags during 21 days of storage. Study Design: In vitro experiments. Methods: Blood samples of approximately 450 ml per blood bag were obtained from six haematologically stable horses. Bags of whole blood were refrigerated for 2 hours at 2° to 6°C, after which each bag was inoculated with 1 ml of E. coli diluted in Brain Heart Infusion broth, containing 1×10 8 CFU/mL, and then separated into two groups: experimental (n=7) and control (n=7). In the experimental group bedside leukocyte filters with a prefilter were applied. Blood count, osmotic fragility, percentage of haemolysis, bacterial culture, and serum potassium, protein, albumin, and glucose levels were analysed. For descriptive analysis and comparison of means between groups and between times, Tukey’s test and Pearson’s chi-square test were used for bacterial concentration and filtration efficiency, with significance set at a p-value <0.05 in both tests, while the 95% confidence interval (CI) was calculated. Results: The human leukocyte filter was efficient at leukoreducing equine whole blood inoculated with E. coli, without causing any quantitative reduction in the red series or an increase in osmotic fragility. Main Limitations: The study presented a limited number of blood bags and a reduced storage time. Conclusions: Overall, we found a significant reduction in the number of E. coli when using leukocyte filters. The reduction in the number of E. coli cells during storage in both groups suggests a role of factors such as filtration, storage time, and low temperature in bacterial control, in addition to leukocytes.

The human gut microbiota (GM) is a community of microorganisms that reside in the gastrointestinal tract. Recognized as a critical element of human health, the functions of the GM extend beyond gastrointestinal well-being to influence overall systemic health and susceptibility to disease. Among the other omic sciences, metaproteomics highlights additional facets that make it a highly valuable discipline in the study of GM. Indeed, it allows the protein inventory of complex microbial communities; peptides identified and quantified by liquid chromatography coupled to mass spectrometry analyses and then are mapped to the most likely proteins, taxa and functions by querying specific databases. The aim of this review was to compile comprehensive information on metaproteomic studies of the human GM, with a focus on the bacterial component, to assist newcomers in understanding the methods and types of research conducted in this field. The review outlines key steps in a metaproteomic-based study, such as protein extraction, database selection, and bioinformatic workflow. The importance of standardization is emphasized. In addition, a list of previously published studies is provided as hints for researchers interested in investigating the role of GM in health and disease states.

This study was conducted on 17 horses to investigate the effects of suspected piroplasmosis on serum biomarkers indicative of heart injury. The horses were diagnosed based on clinical and para-clinical examinations. After taking medical histories, blood samples were collected from the jugular vein and serum was separated. Additionally, samples were taken from 16 healthy horses with similar nutritional and management conditions to serve as a control group. Serum biomarkers of heart injury, including cardiac troponin, CK-MB isoenzyme, LDH, and AST, were measured. The mean cardiac troponin levels in the control and affected horses were 0.022±0.01 and 0.048±0.03, respectively, showing a significant difference between the groups (p=0.001). The mean CK-MB and AST levels were significantly higher in the affected group compared to the control group (p=0.001 and p=0.000, respectively). The LDH serum activity in the control group was lower than in the affected group, but the difference was not statistically significant (p=0.202). In conclusion, the findings suggest that suspected piroplasmosis increases serum levels of cardiac troponin and other biomarkers of heart injury.

Chicken is a better protein source for health than red meat. However, consumption of chicken meat has resulted to food poisoning due opportunistic coagulase –negative staphylococci. Treatment failure has increase due antibiotic resistance cause by misused of antibiotics meant for human consumption in poultry farming. This study aimed to identify and assess antibiotic resistance pattern of CoNS in broiler and layer chickens sold in the local markets of Yaoundé. From three Yaoundé markets, 38 chickens were purchased and subsequently euthanatized at the Food and Drug Safety Research Laboratory. The anatomical sites were used for bacteria isolation. Bacterial isolates were identified using the Gram-positive in vitro test kit cards of the VITEK® 2 systems, and antibiotic susceptibility testing was conducted using AST-P580 test cards. 63.16% (24/38) chickens were infected with 39 CoNS, including: Staphylococcus sciuri (79.5%), S. cohnii sbsp. urealyticus (10.2%), S. equorum (7.7%) and S. klossi (2.6%). S. sciuri strains were resistant to fusidic acid (19.4%), moxifloxacin (16.1%), clindamycin (12.9%), and oxyacillin (6.45%). S. cohnii sbsp. urealyticus strains were resistant to Tetracycline (100%), Trimethoprim-sulfamethoxazole (75%), Oxacillin (25%), Fusidic acid (25%), and Cefoxitin screen (100%). Some strains of S. sciuri and S. cohnii sbsp. urealyticus showed multi-drug resistant patterns. Our study revealed that S. sciuri and S. cohnii sbsp. urealyticus are common in layers and broilers in Yaoundé and they exhibited phenotypic antibiotic resistance. It implies that CoNS may be able to act as both resistance monitoring sentinels and reservoirs of resistance genes that can be transferred on to other pathogens.