Response Profiles Research Articles

Infrared laser-induced gene expression in single cells characterized by quantitative imaging in Physcomitrium patens.

A spatiotemporal understanding of gene function requires the precise control of gene expression in each cell. Here, we use an infrared laser-evoked gene operator (IR-LEGO) system to induce gene expression at the single-cell level in the moss Physcomitrium patens by heating a living cell with an IR laser and thereby activating the heat shock response. We identify the laser irradiation conditions that provide higher inducibility with lower invasiveness by changing the laser power and irradiation duration. Furthermore, we quantitatively characterize the induction profile of the heat shock response using a heat-induced fluorescence reporter system after the IR laser irradiation of single cells under different conditions. Our data indicate that IR laser irradiation with long duration leads to higher inducibility according to increase in the laser power but not vice versa, and that the higher laser power even without conferring apparent damage to the cells decelerates and/or delayed gene induction. We define the temporal shift in expression as a function of onset and duration according to laser power and irradiation duration. This study contributes to the versatile application of IR-LEGO in plants and improves our understanding of heat shock-induced gene expression.

Cardiovascular reactivity during conversations about discrimination is buffered by social support among U.S. Latines.

Racial discrimination is conceptualized as an acute and chronic stressor. Like other acute stressors, lab-based studies demonstrate acute effects of discrimination-related stressors on stress-related cardiovascular outcomes, including total cardiac output, blood pressure, and indices of sympathetic and parasympathetic nervous system activity. Critically, it is important to understand how individual and social factors buffer the experience of race-related acute stress. The current study extends existing work by measuring cardiovascular indices of stress during conversations about racial/ethnic discrimination and examines the moderating role of social support. Latine/Hispanic participants (N = 97) talked about personal discrimination experiences with either a close other or a research assistant they had never previously met. Participants in both conditions exhibited cardiovascular reactivity indicative of stress during the conversation. Additionally, patterns of reactivity reflected a more adaptive stress response and recovery profile when participants talked about discriminatory experiences with a close other relative to a stranger (less parasympathetic withdrawal during the stressor and more parasympathetic rebound during recovery). These patterns are consistent with a stress buffering account of social support, which suggests social bonds and community-level support are critical to consider in interventions to mitigate the harms of experiencing discrimination and prevent chronic health disparities.

Multimodal AI/ML for discovering novel biomarkers and predicting disease using multi-omics profiles of patients with cardiovascular diseases

Cardiovascular diseases (CVDs) are complex, multifactorial conditions that require personalized assessment and treatment. Advancements in multi-omics technologies, namely RNA sequencing and whole-genome sequencing, have provided translational researchers with a comprehensive view of the human genome. The efficient synthesis and analysis of this data through integrated approach that characterizes genetic variants alongside expression patterns linked to emerging phenotypes, can reveal novel biomarkers and enable the segmentation of patient populations based on personalized risk factors. In this study, we present a cutting-edge methodology rooted in the integration of traditional bioinformatics, classical statistics, and multimodal machine learning techniques. Our approach has the potential to uncover the intricate mechanisms underlying CVD, enabling patient-specific risk and response profiling. We sourced transcriptomic expression data and single nucleotide polymorphisms (SNPs) from both CVD patients and healthy controls. By integrating these multi-omics datasets with clinical demographic information, we generated patient-specific profiles. Utilizing a robust feature selection approach, we identified a signature of 27 transcriptomic features and SNPs that are effective predictors of CVD. Differential expression analysis, combined with minimum redundancy maximum relevance feature selection, highlighted biomarkers that explain the disease phenotype. This approach prioritizes both biological relevance and efficiency in machine learning. We employed Combination Annotation Dependent Depletion scores and allele frequencies to identify variants with pathogenic characteristics in CVD patients. Classification models trained on this signature demonstrated high-accuracy predictions for CVD. The best performing of these models was an XGBoost classifier optimized via Bayesian hyperparameter tuning, which was able to correctly classify all patients in our test dataset. Using SHapley Additive exPlanations, we created risk assessments for patients, offering further contextualization of these predictions in a clinical setting. Across the cohort, RPL36AP37 and HBA1 were scored as the most important biomarkers for predicting CVDs. A comprehensive literature review revealed that a substantial portion of the diagnostic biomarkers identified have previously been associated with CVD. The framework we propose in this study is unbiased and generalizable to other diseases and disorders.

Impact of maternal high-fat diet on offspring gut microbiota during short-term high-fat diet exposure in mice.

Alterations in the gut microbiome have been linked to obesity, with maternal high-fat diet (HF) playing a role in shaping offspring microbiome composition. However, the sex-specific responses to maternal HF diet and the impact of subsequent dietary challenges remain unclear. This study investigated the effects of maternal HF diet on offspring gut microbiota structure and predicted functional profile in response to short-term postnatal HF diet exposure with a focus on sex-specific responses. Female and male offspring of maternal control (C) diet or maternal HF diet were weaned onto C diet or HF diet. Offspring were euthanized at 13 weeks of age and cecal contents were collected for bacterial taxonomic profiling. Maternal HF diet reduced α-diversity, notably in male offspring weaned onto HF diet. Sex-specific differences were observed in the gut microbial composition and predicted functional potential. Furthermore, the influence of maternal diet on bacterial community structure and functional potential varied depending on postnatal diet. Maternal HF diet led to increased relative abundance of Corynebacterium in female offspring and decreased abundance of Akkermansia and Roseburia in male offspring. These findings underscore the sexually dimorphic nature of maternal HF diet effects on gut microbiota composition and function, with implications for developmental programming and metabolic health.

The Relationship between Event Boundary Strength and Pattern Shifts across the Cortical Hierarchy during Naturalistic Movie-viewing.

Our continuous experience is spontaneously segmented by the brain into discrete events. However, the beginning of a new event (an event boundary) is not always sharply identifiable: Phenomenologically, event boundaries vary in salience. How are the response profiles of cortical areas at event boundaries modulated by boundary strength during complex, naturalistic movie-viewing? Do cortical responses scale in a graded manner with boundary strength, or do they merely detect boundaries in a binary fashion? We measured "cortical boundary shifts" as transient changes in multivoxel patterns at event boundaries with different strengths (weak, moderate, and strong), determined by across-participant agreement. Cortical regions with different processing timescales were examined. In auditory areas, which have short timescales, cortical boundary shifts exhibited a clearly graded profile in both group-level and individual-level analyses. In cortical areas with long timescales, including the default mode network, boundary strength modulated pattern shift magnitude at the individual participant level. We also observed a positive relationship between boundary strength and the extent of temporal alignment of boundary shifts across different levels of the cortical hierarchy. In addition, hippocampal activity was highest at event boundaries for which cortical boundary shifts were most aligned across hierarchical levels. Overall, we found that event boundary strength modulated cortical pattern shifts strongly in sensory areas and more weakly in higher-level areas and that stronger boundaries were associated with greater alignment of these shifts across the cortical hierarchy.

Profile of immune response during nasal challenge with dermatophagoides pteronyssinus in subjects with allergic airway diseases

BackgroundT lymphocyte helper (Th) 2 plays the main role in pathogenesis of allergic airway diseases (AAD). Recent studies showed that interleukin (IL) 33, Th17 and Th22 also may be involved in allergic inflammation. The aim is to evaluate cytokine level before and after nasal challenge with Dermatophagoides pteronyssinus in patients with AAD.MethodsPatients with persistent allergic rhinitis (AR) with or without allergic asthma (AA) allergic to house dust mite and healthy individuals underwent nasal challenge with Dermatophagoides pteronyssinus. Measurements of IL-13, IL-17, IL-22 and IL-33 in serum and nasal lavage were performed before, 2 and 22 h after nasal challenge by ELISA.Results. Ten patients with AR only, 6 patients with AR and AA and 7 healthy individuals were involved in the study. Serum IL-22 level significantly increased in patients with AR and AA and nasal lavage IL-22 tended to increase in patients with AAD after nasal challenge. Serum IL-13 level tended to increase in patients with AR and AA. IL-13 level in nasal lavage fluid decreased at 22 h after nasal challenge in patients with AR only. IL-17 level in serum and nasal lavage decreased in patients with AAD. Serum IL-33 tended to increase after nasal challenge whereas IL-33 in nasal lavage significantly decreased.ConclusionCytokine profile differs between local and systemic compartments and between patients with allergic rhinitis only and patients with allergic rhinitis and asthma after nasal challenge.

Effect of working remotely on new professionals’ learning and adjustment during the first five weeks after professional entry

Purpose This study aimed to investigate the effect of working remotely on new professionals’ learning and adjustment. Organizational socialization is the process of learning and adjusting to a new professional role. Among new professionals working on-site, this learning and adjustment is indicated by a development of role clarity, task mastery and social acceptance. Less is known about the process when working remotely. This was recognized as a key organizational challenge following the onset of the COVID-19 pandemic. Design/methodology/approach In this study, with a longitudinal design with 242 graduates and weekly data collections for the first five weeks following professional entry in 2021, the authors compared the learning and adjustment among individuals working on-site, in hybrid or remotely using longitudinal analyses of mean response profiles. Findings The group-by-time interaction effects were not statistically significant (i.e. no differences were found in the adjustment of the new professionals of the three groups). Originality/value These results indicate that working remotely does not jeopardize the organizational socialization process. Furthermore, a marginally statistically significant result indicated that participants working only remotely experienced a greater development of task mastery over time: This suggests that remote work may even benefit learning and professional adjustment. Theoretical and practical implications of the results are discussed.

Selective Cytotoxicity and Gene Expression Profiles in Response to Methanolic Extract of Phyllanthus amarus Extract against MCF-7 Breast Cancer Cells

Background Breast cancer, a malignant tumor, is the most common cancer type among women worldwide. Conventional chemotherapy treatments for breast cancer often cause adverse side effects in normal tissues and can lead to treatment failure. Plant-derived natural compounds offer an effective alternative with fewer side effects for cancer patients. Phyllanthus amarus is a medicinal plant widely distributed in China, India, and Brazil and reported to be used for the treatment of various types of cancer. Purpose This study was aimed to investigate the anticancer efficacy of methanolic extract of P. amarus against MCF-7 breast cancer cells. Methods We probed the anticancer activity in MCF-7 breast cancer cells by isolating the methanolic extract of P. amarus leaf extract (MEPA). The standard chemotherapy drug docetaxel is combined with MEPA to increase the drug efficacy. Moreover, the intracellular reactive oxygen species (ROS), alterations in mitochondrial membrane potential (MMP), nuclear condensation, and apoptotic activation were investigated in MCF-7 cells. Additionally, the customized PCR array comprising of cell cycle, apoptosis, mTOR, and JAK-STAT-related genes was studied during different MEPA treatments. Results In the MCF-7 breast cancer cells, the MEPA and docetaxel combination demonstrated strong cytotoxicity, with IC50 values of 45 and 2.6 µg/mL, respectively. MEPA and docetaxel together exhibited enhanced alterations in MMP and increased generation of ROS in MCF-7 cells. Furthermore, the combination of docetaxel with MEPA induces nuclear condensation and apoptotic cell death. During MEPA treatment, the gene expression profiles in MCF-7 cells were accessed. The JAK-STAT, mTOR signaling pathway, apoptosis, and cell growth-related genes were strongly affected by the dose-dependent administration of MEPA. Conclusion This study suggests that MEPA could be a useful alternative treatment for breast cancer. When combined with traditional chemotherapy, MEPA might offer better results with fewer side effects. More in vivo studies are needed to confirm MEPA’s effectiveness in animal models.

Sex-specific immune responses to COVID-19 vaccination in end-stage renal disease patients

Abstract Background End-stage renal disease (ESRD) patients have muted memory B cell formation and reduced humoral responses to COVID-19 vaccination; however, early innate immune responses have yet to be characterized. Sex-stratification is also limited in COVID-19 vaccination research. Methods We collected blood before (BD1) and 1-4 days post-dose 1 (PD1) of BNT162b2 vaccination for RNA-sequencing in ESRD patients (n = 35 BD1; 18 PD1) and healthy controls (HC) (n = 31 BD1; 30 PD1). Additionally, 20 plasma cytokines were quantified in ESRD patients (n = 39 BD1, 35 PD1) and HC (34 BD1, 15 PD1). Results Transcriptional profiling of vaccine responses identified 125 significantly differentially expressed genes (DEG) (padj<0.04) in ESRD patients and 107 DEGs (padj<0.05) in HC. 71 DEGs were shared, 54 unique to ESRD, and 36 unique to HC. DEG, pathway analyses, and cytokine responses in the combined dataset showed ESRD patients were more inflamed than HC at baseline, with an elevated inflammatory cytokine profile compared to HC. These results were driven by female ESRD patients where IL-2, IL-10, and IP-10 were more significant in females (p < 0.001) compared to males (p < 0.01). While IL-6, IFN-γ, IL-13, eotaxin, were exclusively associated in females (p < 0.05). Healthy females also had a stronger immunological response to vaccination compared to healthy males. Conclusions Despite baseline inflammation, ESRD patients were able to mount similar early immune responses to vaccination as HC, with females in both populations more reactogenic than males. Sex-stratification is recommended for ongoing immunological research to better understand unique responses to COVID-19 vaccination. Key messages • End-stage renal disease patients have similar early innate immune responses to COVID-19 vaccination as healthy controls. • Sex-stratification is important to identify unique immunological responses that may be leveraged for sex-specific vaccination strategies.

Autonomic response and attachment style in disruptive mood dysregulation disorder.

Disruptive mood dysregulation disorder (DMDD) is characterised by severe emotion regulation difficulties, particularly anger and irritability, in children. Despite the impact of attachment on emotional and behavioural regulation, the link between attachment style and DMDD is under-researched. This study investigated whether attachment style and parasympathetic regulation differentiate the response profiles to frustrating conditions between children diagnosed with DMDD and controls. Participants were assessed at schools in Johannesburg, Gauteng, South Africa. Thirty participants were divided into two matched groups (n DMDD = 15; n Control = 15) and assessed. Respiratory sinus arrhythmia (RSA) and heart period were measured during an Affective Posner Task, inducing frustration. Attachment style was assessed using the Attachment Style Classification Questionnaire for children. Parents of children with DMDD completed a social interaction problems questionnaire. The DMDD group showed a higher prevalence of avoidant attachment style (p = 0.013) compared to controls. Both groups displayed adaptive vagal withdrawal and recovery during the task (p = 0.005; p = 0.021). Controls had significantly higher heart period throughout the assessment (game 1: p = 0.006; game 2: p = 0.013; game 3: p = 0.007). In the DMDD group, lower vagal tone during frustration correlated with more social interaction problems (p = 0.049). The study demonstrates a potential link between attachment style and altered physiological state in children with DMDD. The findings provide insight into possible atypical vagal regulation of the heart and avoidant attachment styles in DMDD, highlighting potential therapeutic and intervention targets.

Differential Host Gene Expression in Response to Infection by Different Mycobacterium tuberculosis Strains—A Pilot Study

Tuberculosis (TB) represents a global public health threat and is a leading cause of morbidity and mortality worldwide. Effective control of TB is complicated with the emergence of multidrug resistance. Yet, there is a fundamental gap in understanding the complex and dynamic interactions between different Mycobacterium tuberculosis strains and the host. In this pilot study, we investigated the host immune response to different M. tuberculosis strains, including drug-sensitive avirulent or virulent, and rifampin-resistant or isoniazid-resistant virulent strains in human THP-1 cells. We identified major differences in the gene expression profiles in response to infection with these strains. The expression of IDO1 and IL-1β in the infected cells was stronger in all virulent M. tuberculosis strains. The most striking result was the overexpression of many interferon-stimulated genes (ISGs) in cells infected with the isoniazid-resistant strain, compared to the rifampin-resistant and the drug-sensitive strains. Our data indicate that infection with the isoniazid-resistant M. tuberculosis strain preferentially resulted in cGAS-STING/STAT1 activation, which induced a characteristic host immune response. These findings reveal complex gene signatures and a dynamic variation in the immune response to infection by different M. tuberculosis strains.

Analyzing early childhood allergy prevention motivation of mothers of infants and its predictors using latent class analysis and structural equation modelling

BackgroundAllergic diseases are among the most common chronic diseases in childhood. Early childhood allergy prevention (ECAP) behaviors of those caring for the infant during pregnancy and the first months of life may influence the risk of allergy development over the life course. Motivation and intention to use appropriate primary ECAP measures are thus of critical importance.AimsTo characterize parental ECAP motivation, (a) valid indicators will be developed and (b) typical parental characteristics will be identified. (c) According to socio-cognitive models, the predictive value of parental risk perception, control belief and self-efficacy for parental ECAP motivation shall be determined.MethodA sample of N = 343 (expectant) mothers of infants completed a questionnaire on self-reported ECAP motivation, risk perception, control belief, and self-efficacy. The cross-sectional data were analyzed using latent class analysis and structural equation modelling including nominal regression models.ResultsFour typical maternal response profiles (motivated to a customary degree, 70%; motivated to use primary preventive measures, 17.8%; reluctant towards new prevention measures, 6.4%; highly motivated to apply preventive measures in case of an existing allergy, 5.8%) could be identified for the items on ECAP motivation. After splitting the model variables “risk perception” (allergy vs. allergy-associated general health problems) and “self-efficacy” (trust vs. insecurity) a satisfactory model-fit was achieved (CFI = .939; RMSEA = .064). Particularly, increased “risk perception-allergy” (OR = 1.655) and “self-efficacy-insecurity” (OR = 2.013) as well as lower “risk perception-general health” (OR = 0.555) and “control belief” (OR = 0.217), respectively, are associated with higher ECAP motivation.ConclusionThe use of ECAP-measures by parents to protect their newborns from allergies is important, but there are deficiencies in their implementation. Based on a social cognitive model approach, predictive characteristics could be identified, which are associated with increased motivation to implement ECAP-measures. For public health our findings provide a promising basis for conception of behavioral and environmental ECAP prevention measures and their motivated implementation by parents.

Predictive immunoinformatics reveal promising safety and anti-onchocerciasis protective immune response profiles to vaccine candidates (Ov-RAL-2 and Ov-103) in anticipation of phase I clinical trials.

Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025. Notably, Ov-RAL-2 and Ov-103 antigens have shown great promise during pre-clinical development, however, the overall success rate of vaccine candidates during clinical development remains relatively low due to certain adverse effects and immunogenic limitations. This study, thus, aimed at predicting the safety and immunogenicity of Ov-RAL-2 and Ov-103 potential onchocerciasis vaccine candidates prior to clinical trials. Advanced molecular simulation models and analytical immunoinformatics algorithms were applied to predict potential adverse side effects and efficacy of these antigens in humans. The analyses revealed that both Ov-RAL-2 and Ov-103 demonstrate favourable safety profiles as toxicogenic and allergenic epitopes were found to be absent within each antigen. Also, both antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes (antibodies, cytokines, and T- Cell epitopes) associated with protective immunity against onchocerciasis. In agreement, virtual vaccination simulation forecasted heightened, but sustained levels of primary and secondary protective immune responses to both vaccine candidates over time. Ov-103 was predicted to be non-camouflageable, as it lacked epitopes identical to protein sequences in the human proteome. Indeed, both antigens were able to bind with high affinity and activate the innate immune TLR4 receptor, implying efficient immune recognition. These findings suggest that Ov-RAL-2 and Ov-103 can induce sufficient protective responses through diverse humoral and cellular mechanisms. Overall, our study provides additional layer of evidence for advancing the clinical development of both vaccine candidates against onchocerciasis.

Clinical pilot of bacterial transcriptional profiling as a combined genotypic and phenotypic antimicrobial susceptibility test.

Antimicrobial resistance is a growing health threat, but standard methods for determining antibiotic susceptibility are slow and can delay optimal treatment, which is especially consequential in severe infections such as bacteremia. Novel approaches for rapid susceptibility profiling have emerged that characterize either bacterial response to antibiotics (phenotype) or detect specific resistance genes (genotype). Genotypic and Phenotypic AST through RNA detection (GoPhAST-R) is a novel assay, performed directly on positive blood cultures, that integrates rapid transcriptional response profiling with the detection of key resistance gene transcripts, thereby providing simultaneous data on both phenotype and genotype. Here, we performed the first clinical pilot of GoPhAST-R on 42 positive blood cultures: 26 growing Escherichia coli, 15 growing Klebsiella pneumoniae, and 1 with both. An aliquot of each positive blood culture was exposed to nine different antibiotics, lysed, and underwent rapid transcriptional profiling on the NanoString platform; results were analyzed using an in-house susceptibility classification algorithm. GoPhAST-R achieved 95% overall agreement with standard antimicrobial susceptibility testing methods, with the highest agreement for beta-lactams (98%) and the lowest for fluoroquinolones (88%). Epidemic resistance genes including the extended spectrum beta-lactamase blaCTX-M-15 and the carbapenemase blaKPC were also detected within the population. This study demonstrates the clinical feasibility of using transcriptional response profiling for rapid resistance determination, although further validation with larger and more diverse bacterial populations will be essential in future work. GoPhAST-R represents a promising new approach for rapid and comprehensive antibiotic susceptibility testing in clinical settings.IMPORTANCEExposure to antibiotics causes differential transcriptional signatures in susceptible vs resistant bacteria. These differences can be leveraged to rapidly predict resistance profiles of Escherichia coli and Klebsiella pneumoniae in clinically positive blood cultures.

Comparative Analysis of Inverse Problem-Solving Techniques: Integrating Deep Learning with Advanced Optimization Methods

This paper presents a comparative analysis of four distinct approaches to solving inverse problems in engineering and scientific applications. The studies under comparison integrate deep learning techniques, specifically using TensorFlow, with various optimization methods: Genetic Algorithm (GA), Ant Colony Optimization (ACO), LMFIT (employing Nelder-Mead and Powell methods), and Particle Swarm Optimization (PSO). All four approaches aim to predict design parameters for achieving desired response profiles. This analysis examines the methodologies, performance metrics, and unique features of each approach, providing insights into their relative strengths and potential applications.

Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone-sensitive prostate cancer: A multicenter study.

We aimed to assess the differential efficacy and safety of androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, and apalutamide, in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a real-world practice setting. We retrospectively reviewed the records of consequent 668 patients with mHSPC treated with ARPI plus androgen deprivation therapy between September 2015 and December 2023. Based on the LATITUDE criteria, the comparison among abiraterone, enzalutamide, and apalutamide was exclusively conducted in high-risk patients. Prostate-specific antigen (PSA) responses such as the achievement of 95% and 99% PSA decline, overall survival (OS), cancer-specific survival (CSS), time to castration-resistant prostate cancer (CRPC), and the incidence of adverse events (AEs) were compared. All two-group comparisons relied on propensity score matching (PSM) to minimize the effect on possible confounders. In total, 297 patients with high-risk mHSPC treated with abiraterone, 127 with enzalutamide, and 142 with apalutamide were compared. There were no differences in time to CRPC (p = 0.13), OS (p = 0.7), and CSS (p = 0.5) among the three ARPIs. No differences were observed in the achievement rates for 95% PSA decline at 3 months among the three ARPIs, while abiraterone was significantly better in 99% PSA decline achievement compared to apalutamide (72% vs. 57%, p = 0.003). The aforementioned oncologic outcomes were sustained even when performing PSM analyzes. Although skin rash for APA (34%) was the highest incidence of AEs, there were no differences in the rates of severe AEs across the three ARPIs. Enzalutamide resulted in the lowest treatment discontinuation rates (10%) other than disease progression compared to the other regimens. Abiraterone, enzalutamide, and apalutamide have comparable oncologic outcomes in terms of OS, CSS, and time to CRPC in patients with high-risk mHSPC. Our data on differential treatment discontinuation rates, PSA response, and AE profiles can help guide clinical decision-making.

Mosquito taste responses to human and floral cues guide biting and feeding.

The taste system controls many insect behaviours, yet little is known about how tastants are encoded in mosquitoes or how they regulate critical behaviours. Here we examine how taste stimuli are encoded by Aedes albopictus mosquitoes-a highly invasive disease vector-and how these cues influence biting, feeding and egg laying. We find that neurons of the labellum, the major taste organ of the head, differentially encode a wide variety of human and other cues. We identify three functional classes of taste sensilla with an expansive coding capacity. In addition to excitatory responses, we identify prevalent inhibitory responses, which are predictive of biting behaviour. Certain bitter compounds suppress physiological and behavioural responses to sugar, suggesting their use as potent stop signals against appetitive cues. Complex cues, including human sweat, nectar and egg-laying site water, elicit distinct response profiles from the neuronal repertoire. We identify key tastants on human skin and in sweat that synergistically promote biting behaviours. Transcriptomic profiling identifies taste receptors that could be targeted to disrupt behaviours. Our study sheds light on key features of the taste system that suggest new ways of manipulating chemosensory function and controlling mosquito vectors.

Comprehensive identification of GASA genes in sunflower and expression profiling in response to drought

Drought stress poses a critical threat to global crop yields and sustainable agriculture. The GASA genes are recognized for their pivotal role in stress tolerance and plant growth, but little is known about how they function in sunflowers. The investigation aimed to identify and elucidate the role of HaGASA genes in conferring sunflowers with drought tolerance. Twenty-seven different HaGASA gene family members were found in this study that were inconsistently located across eleven sunflower chromosomes. Phylogeny analysis revealed that the sunflower HaGASA genes were divided into five subgroups by comparing GASA genes with those from Arabidopsis, peanut, and soybean, with members within each subgroup displaying similar conserved motifs and gene structures. In-silico evaluation of cis-regulatory elements indicated the existence of specific elements associated with stress-responsiveness being the most abundant, followed by hormone, light, and growth-responsive elements. Transcriptomic data from the NCBI database was utilized to assess the HaGASA genes expression profile in different sunflower varieties under drought conditions. The HaGASA genes expression across ten sunflower genotypes under drought stress, revealed 14 differentially expressed HaGASA genes, implying their active role in the plant’s stress response. The expression in different organs revealed that HaGASA2, HaGASA11, HaGASA17, HaGASA19, HaGASA21 and HaGASA26 displayed maximum expression in the stem. Our findings implicate HaGASA genes in mediating sunflower growth maintenance and adaptation to abiotic stress, particularly drought. The findings, taken together, provided a basic understanding of the structure and potential functions of HaGASA genes, setting the framework for further functional investigations into their roles in drought stress mitigation and crop improvement strategies.

(+) Anatoxin-a elicits differential survival, photolocomotor behavior, and gene expression in two alternative vertebrate models

Anatoxin-a is a globally occurring, yet understudied, chiral cyanobacterial toxin that threatens public health and the environment. It has led to numerous dog. livestock and bird poisonings and although it has been studied in rodent models, comparatively little research has occurred in aquatic species. To advance a comparative toxicology understanding of this toxin in alternative vertebrate models, developing zebrafish and fathead minnow were exposed to environmentally relevant and elevated levels (13–4400 μg/L) of (+) anatoxin-a to examine potential mortality and sublethal effects, including photolocomotor behavior and gene expression responses. We observed significantly higher mortality (p < 0.05) in fathead minnows exposed to ≥ 1400 μg/L (65 – 83 % survival versus 97 % in controls). Locomotor response profiles for zebrafish typically displayed hypoactivity after exposure to (+) anatoxin-a in both light and dark periods, while hyperactivity of fathead minnows was observed at the lowest treatment level, but only in light conditions. Gene expression in zebrafish was significantly (p < 0.05) downregulated for mbp, which is associated with myelin sheath formation, and elavl3, which is involved in neurogenesis, along with cyp3a65 and gst, two genes related to phase I and II metabolism. However, no significant (p > 0.05) transcriptional changes were observed in the fathead minnow model. These differential responses between commonly employed species employed as alternative vertebrate models in toxicology research and chemicals risk assessments highlight the need for more comparative studies to understand sensitivities and variations in organismal response. Furthermore, we identified higher mortality, refractory behavioral effects, and gene expression in (+) anatoxin-a exposed fish when compared to previously reported (±) anatoxin-a (racemic 50:50 enantiomer mixture) studies, which is frequently used as a surrogate chemical for experimental work. Our findings identify the importance of understanding species and enantiomer specific effects of natural toxins.

Quantitative physics-physiology relationship modeling of human emotional response to Shu music.

Music perception is one of the most complex human neurophysiological phenomena invoked by sensory stimuli, which infers an internal representation of the structured events present in a piece of music and then forms long-term echoic memory for the music. An intrinsic relationship between the basic acoustic property (physics) of music and human emotional response (physiology) to the music is suggested, which can be statistically modeled and explained by using a novel notion termed as quantitative physics-physiology relationship (QPPR). Here, we systematically analyzed the complex response profile of people to traditional/ancient music in the Shu area, a geographical concept located in the Southwest China and one of three major origins of the Chinese nation. Chill was utilized as an indicator to characterize the response strength of 18 subjects to an in-house compiled repertoire of 86 music samples, consequently creating a systematic subject-to-sample response (SSTSR) profile consisting of 1,548 (18 × 86) paired chill elements. The multivariate statistical correlation of measured chill values with acoustic features and personal attributes was modeled by using random forest (RF) regression in a supervised manner, which was compared with linear partial least square (PLS) and non-linear support vector machine (SVM). The RF model exhibits possessed strong fitting ability (r F 2 = 0.857), good generalization capability (r P 2 = 0.712), and out-of-bag (OOB) predictability (r O 2 = 0.731) as compared to SVM and, particularly, PLS, suggesting that the RF-based QPPR approach is able to explain and predict the emotional change upon musical arousal. It is imparted that there is an underlying relationship between the acoustic physical property of music and the physiological reaction of the audience listening to the music, in which the rhythm contributes significantly to emotional response relative to timbre and pitch. In addition, individual differences, characterized by personal attributes, is also responsible for the response, in which gender and age are most important.