Biological Threats Research Articles

A Review on Molecular Mechanism of Plant Immunity against Fungal Pathogens

The molecular mechanisms of plant immunity, with a particular focus on how plants defend themselves against fungal pathogens. Plant immunity is a complex, multi-layered system involving pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), which together form a robust defense against a wide array of pathogens. Advances in genomics and transcriptomics have significantly enhanced our understanding of these immune mechanisms by identifying key resistance (R) genes and uncovering the transcriptional networks that regulate immune responses. Proteomics and metabolomics further elucidate the functional aspects of immunity, revealing how proteins and metabolites are mobilized during pathogen attack. The advent of gene editing technologies, particularly CRISPR-Cas9, has opened new avenues for enhancing plant immunity by enabling precise modifications of genes associated with disease resistance. The ever-evolving nature of fungal pathogens, driven by genetic diversity and environmental changes, poses ongoing challenges. Emerging pathogens and the breakdown of existing resistance in crops underscore the need for durable resistance strategies, which can be achieved through the pyramiding of multiple R genes, susceptibility gene knockouts, and the harnessing of beneficial plant microbiomes. As climate change exacerbates the spread and virulence of fungal pathogens, developing climate-resilient crops that can withstand both abiotic stresses and pathogen pressures is becoming increasingly important. Future research should prioritize understanding the molecular dynamics of plant-pathogen interactions, leveraging new technologies for crop improvement, and fostering interdisciplinary collaboration to address these challenges. Ultimately, translating these scientific advances into practical applications will be crucial for ensuring global food security and sustainable agricultural systems in the face of mounting environmental and biological threats.

ANTICIPATING BIOSECURITY HAZARDS: DISTRIBUTION AND RECOGNITION OF BIOLOGICAL THREATS

Understanding the potential biological weapons that can be created, the technologies involved, and the entities capable of producing them is crucial for biosecurity. Equally important is comprehending the various targets a biological weapon might be aimed at, the deployment methods, and available detection strategies to counteract illegal biological threats. This chapter delves into these aspects, starting with methods of deployment. The Center for Disease Control and Prevention (CDC) categorizes disease transmission into direct and indirect modes. Direct transmission involves contact with an infected person or environmental reservoir, including droplet spread, proven highly effective in densely populated areas. Indirect transmission occurs through contaminated objects or vectors. Vehicle-based transmission involves contaminating inanimate objects like food, water, and biological products. Vector-based transmission involves organisms carrying and transmitting pathogens. Airborne transmission, receiving significant attention for its potential in biological attacks, involves pathogens suspended in the air, posing significant risks, especially in crowded areas. Biological weapons could target humans, agriculture, technology, and the environment. Attacks on humans, often the focus of biosecurity efforts, pose catastrophic outcomes. State-sponsored programs often focus on human pathogens like Bacillus anthracis and Yersinia pestis. Agroterrorism, targeting agriculture and livestock, can lead to economic losses and social instability. Attacks on technology, utilizing synthetic biology, have shown the potential to manipulate DNA to store and deploy malicious code, highlighting vulnerabilities in sequencing systems. While attacks on the environment remain theoretical, advancements in gene drives raise concerns about manipulating ecosystems. Effective biosecurity involves pre- and post-deployment screening techniques. Pre-deployment screening, particularly gene synthesis, focuses on preventing the acquisition of DNA fragments for weapon production. Current measures involve background checks and screening against pathogen lists, yet gaps exist, including inadequate international policies and the potential to hide malicious sequences within longer ones. Post-deployment detection relies on traditional molecular diagnostic methods, but synthetic pathogens may evade detection, necessitating ongoing advancements in detection techniques. Real-time sensors and biosensors offer promising avenues for quick and accurate pathogen recognition, although challenges remain in detecting novel pathogens against a natural background. In conclusion, understanding the range of biological weapons, their potential targets, deployment methods, and detection strategies is essential for effective biosecurity. Continued research and advancements in detection technologies are crucial to staying ahead of evolving biological threats, ensuring a safer and more secure future.

Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E.

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine. Mice vaccinated with CS-Hc/E exhibited superior antibody titers compared to those receiving Hc/E alone. To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E- key contributors to the vast majority of human botulism-we conjugated CS-Hc/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A and BoNT/B. This chimeric protein includes the binding domain of BoNT/A, along with the protease-inactive light chain and translocation domains of BoNT/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT/A, BoNT/B, and BoNT/E. Our findings highlight EBA's potential as a stable and effective broad-spectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies.

Thyroid activity and human physical and mental health: environmental and clinical aspects

Based on the results of theoretical and practical research, the article defines the ecological and clinical aspects of human physical and mental health in connection with the activity of the thyroid gland in normal and pathological conditions. In general, quantitative and qualitative indicators of health as a bio-psycho-social and morpho-functional phenomenon are closely related to humoral and nervous mechanisms of regulation, as well as the body's reactivity, taking into account age and gender characteristics. Special attention should be paid to studies on the influence of thyroid activity on the formation of group reactivity (constitution), as well as nonspecific reactivity, including stress as a general adaptation syndrome. At the same time, the conditions of potential and real biological and military threats, as well as various forms of human activity, including the educational process, are accompanied by physiological and psychological stress, which requires appropriate interdisciplinary research on human stress resistance as a significant component of physical and mental health. In this regard, during the training, methods for diagnosing the body's stress resistance were tested according to certain morphological indicators and indices, taking into account the activity of the thyroid gland and its functional influence on the formation of the human constitution. In addition, taking into account environmental and social conditions, the potential levels of interdisciplinary research on the comprehensive assessment of human physical and mental health indicators are identified.

Strategies to Ensure Effective and Safe Patient Care in Intensive Care Units During Biological Events: A Delphi Study.

Throughout history, humanity has faced numerous biological threats that have resulted in catastrophic epidemics. The challenges (Fear, uncertainties, failure of care, etc) posed by epidemics necessitate the implementation of a variety of strategies to contain them. This study was conducted to identify strategies to ensure effective and safe patient care during biological events. This study is phase of a larger research project that used the Delphi method in its third stage. The objective was to address the need for effective and safe care in intensive care units (ICUs) during biological events like the COVID-19 pandemic. The Delphi questionnaire was constructed using insights from the first two phases of the study: the qualitative component and the integrative review phase. The Delphi method was implemented over three rounds, with experts selected through purposive sampling. The Kendall coefficient measured the degree of consensus among the experts' opinions. The strategies identified for the provision of effective and safe patient care during biological events were categorized into 10 main categories, which were further divided into related subcategories. Identifying and implementing strategies to improve care in intensive care units can improve patient care during crises, such as new disease outbreaks. By identifying these strategies, biological events similar to the COVID-19 pandemic can be managed more effectively. Further research is warranted to explore strategies to improve patient care in other healthcare sectors.

Epidemiological features and psychoneurological consequences of infection of people with the Nipah virus

The lecture outlines modern ideas about the etiology, features of the epidemic process, mechanisms of damage to the human body, clinical manifestations, diagnosis, treatment and prevention of infection caused by the Nipah virus. Particular attention is paid to the characteristics of individual outbreaks of the infectious process in various geographical regions of the world, early and long-term psychopathological, neurological and cognitive consequences due to human infection with the Nipah virus. The risk factors for the emergence and rapid spread of infection with a very high mortality rate, reaching 100%, are emphasized, which determines the high pandemic potential and hidden threats to human society. Recommendations are outlined for the prevention of transmission of infection caused by the Nipah virus at all levels: from animals to humans, from humans to humans, in medical institutions, which, in the absence of effective vaccine prevention and specific antiviral treatment, are the basis for containing the spread of the infectious process. In this regard, measures taken and planned to provide patients and contact persons with adequate medical and psychological care, features of the development and implementation of effective anti-epidemic, clinical diagnostic algorithms, timely and high-quality social and hygienic monitoring of environmental objects against the backdrop of increasing biological threats from outside, and within the country will minimize the risks of biological threats. The lecture is intended for doctors of various specialties, including infectious disease specialists, epidemiologists, general practitioners, neurologists, psychiatrists, laboratory diagnosticians, radiologists etc.

Evaluation of Soldiers' Knowledge and Sense of Threats Regarding Exposure to Biological Risk Factors at the Place of Service.

Exposure to harmful biological agents and the level of knowledge about specific risk factors are extremely important topics, especially among military personnel. This study evaluates the knowledge and perceptions of soldiers regarding exposure to biological risk factors during their service. This research was conducted using an online survey distributed through the WBBS research panel, in which 1331 soldiers from various demographic groups and ranks participated. The survey assessed awareness of biological threats, the level of knowledge about preventive measures, and the perceived adequacy of occupational health and safety training. The findings reveal that over 80% of respondents possess some level of knowledge about the types of biological agents they may encounter, yet significant gaps remain, particularly in training related to region-specific infectious diseases, with more than 75% of participants having not received such training. Additionally, approximately 5% of respondents reported high exposure, and around 4% reported very high exposure to harmful biological agents, highlighting the need for enhanced educational programs and preventive measures in military contexts. The study underscores the importance of continuous education and training to mitigate risks associated with biological hazards in military environments.

Последствия распространения коронавируса COVID-19 и новых штаммов для развития агропромышленного комплекса и потребительского рынка

The COVID-19 pandemic has become an example of the implementation of global biological threats, which are positioned as challenges to the economy, including the agricultural sector. The subject of the study was changes in food production and in the consumer market for agricultural products amid the consequences of the spread of the COVID-19 coronavirus and potentially dangerous new strains. Since the volume and structure of agricultural exports can serve as indicators of overcoming the challenge to the agro-industrial complex from the consequences of the COVID-19 pandemic, including in conjunction with the influence of the sanctions policies of Western countries, the object of the study was changes in the main indicators of exports of the agro-industrial complex of the Russian Federation at the federal and regional levels for first quarter of 2023 compared to the same period in 2022. Changes in the main indicators of exports of agricultural products were studied both at the federal and regional levels, using the example of agricultural enterprises in the Voronezh region, for the first quarter of 2023 compared to the same period in 2022. As a background for studying the subject field of indicators for overcoming the challenge to the agro-industrial sector from the consequences of the COVID-19 pandemic, changes in the field of food production and in the consumer market for agricultural products were identified and studied. An overview of the main exporting companies in the Voronezh region is presented for the following types of products: grains (wheat, corn, barley); meat and dairy products (pork and pork by-products, beef, butter); products of the oil and fat industry (sunflower oil, cakes, mustard oil). The priority trend for the Russian Federation is the development of deep processing of crop products, in particular grain crops. The basis is the trend of growing consumer demand for food products of plant origin, including those that imitate traditional meat and dairy products. A trend has been noted for the production and consumption of organic products, the implementation of which will contribute to the growth of the competitiveness of domestic agricultural products in the domestic and foreign markets. An important factor in increasing the competitiveness of domestic food in the global and domestic markets is the expansion of production of organic crop and livestock products based on a single unified database of agricultural land that meets the legally established requirements for this category of products.

Tackling Impediments: Bespoke Solutions for Optimized Implant Outcomes

The field of implantology has transformed dental restoration, yet significant challenges persist that can impede successful treatment outcomes. This review examines the technical and biological roadblocks encountered in dental implant procedures, highlighting the vital role of tailored innovations in overcoming these obstacles. Advances in materials science, digital technology, and surgical techniques are crucial for enhancing osseointegration and ensuring overall implant success. Common complications include surgical issues such as infections and nerve damage, prosthetic challenges like misalignment and aesthetic concerns, and biological threats such as peri-implantitis and bone loss. To combat these, proactive management strategies—encompassing meticulous preoperative planning, regular monitoring, and personalized solutions—are essential for improving patient care. This review underscores the importance of interdisciplinary collaboration of prosthodontists, oral surgeons, periodontists and oral radiologists in mitigating risks and presents effective management strategies to optimize outcomes. By elevating awareness of potential complications and implementing precise diagnosis and treatment planning, practitioners can significantly enhance the longevity and effectiveness of dental implants, ultimately securing a better quality of life for patients.

LP-34 Is the incursion of the Asian toad Duttyphrynus melanostictus a possible biological threat in Madagascar? Determination by UHPLC-MS/MS of 5-OH-DMT (Bufotenine) in toad samples

LP-34 Is the incursion of the Asian toad Duttyphrynus melanostictus a possible biological threat in Madagascar? Determination by UHPLC-MS/MS of 5-OH-DMT (Bufotenine) in toad samples

From G.R.I.D. to AIDS &COVID-19 to Long-COVID: Naming and Defining Biological Threats

This article uses the history of the early U.S. case definition of AIDS to question the imperatives in the newly developed Long-COVID (LC) definition. Doing so allows us to think through the role of case definitions in producing meaning in our world and to consider what we can learn about the politics of knowledge creation. By examining the porous boundaries of identity, institutions, and AIDS and placing this history in relation to LC, I argue that the state is doing more than describing and diagnosing these institutional practices, but that hybrid identities are produced by the state through these practices like naming and defining. Comparing these two events in public health reveals the state to be a primary—perhaps the primary—agent in elaborating the contours of identity through disease. I employ an analytic framework based on the institutionalization of "identity stories" established by political scientist Clarissa Rile Hayward to argue that the case definition is a central site where knowledge about disease and identity is built into the structure of political institutions. Identifying how this process happens within institutions provides important political lessons for our current moment and offers opportunities for resistance to health inequities.

Establishing Healthy Breath Baselines With Tin Oxide Sensors: Fundamental Building Blocks for Noninvasive Health Monitoring.

Volatile organic compounds (VOCs) in breath serve as a source of biomarkers for medical conditions relevant to warfighter health including Corona Virus Disease and other potential biological threats. Electronic noses are integrated arrays of gas sensors that are cost-effective and miniaturized devices that rapidly respond to VOCs in exhaled breath. The current study seeks to qualify healthy breath baselines of exhaled VOC profiles through analysis using a commercialized array of metal oxide (MOX) sensors. Subjects were recruited/consented through word of mouth and using posters. For each sample, breath was analyzed using an array of MOX sensors with parameters that were previously established. Data were also collected using a lifestyle questionnaire and from a blood test to assess markers of general health. Sensor data were processed using a feature extraction algorithm, which were analyzed through statistical approaches to identify correlations with confounding factors. Reproducibility was also assessed through relative standard deviation values of sensor features within a single subject and between different volunteers. A total of 164 breath samples were collected from different individuals, and 10 of these volunteers provided an additional 9 samples over 6 months for the longitudinal study. First, data from different subjects were analyzed, and the trends of the 17 extracted features were elucidated. This revealed not only a high degree of correlation between sensors within the array but also between some of the features extracted within a single sensor. This helped guide the removal of multicollinear features for multivariate statistical analyses. No correlations were identified between sensor features and confounding factors of interest (age, body mass index, smoking, and sex) after P-value adjustment, indicating that these variables have an insignificant impact on the observed sensor signal. Finally, the longitudinal replicates were analyzed, and reproducibility assessment showed that the variability between subjects was significantly higher than within replicates of a single volunteer (P-value = .002). Multivariate analyses within the longitudinal data displayed that subjects could not be distinguished from one another, indicating that there may be a universal healthy breath baseline that is not specific to particular individuals. The current study sought to qualify healthy baselines of VOCs in exhaled breath using a MOX sensor array that can be leveraged in the future to detect medical conditions relevant to warfighter health. For example, the results of the study will be useful, as the healthy breath VOC data from the sensor array can be cross-referenced in future studies aiming to use the device to distinguish disease states. Ultimately, the sensors may be integrated into a portable breathalyzer or current military gear to increase warfighter readiness through rapid and noninvasive health monitoring.

BIOGEOGRAPHY AND INVASION BIOLOGY- A THEORETICAL STUDY

Biogeography is a 19th-century discipline of geography that analyses the spatial distribution of creatures such as plants and animals. Biogeography is the scientific study, description, and documentation of the distribution and spread of species around the globe, as well as their environmental variables. Since, Invasion Invading species biology is one of the more recently created fields of biology that deals with the problem of invasive species. The phrase "invasive species" refers to plant and animal species that have been brought to new geographies and ecosystems and compete fiercely with native species that are infringing on their ecological area. They acquire and use space, soil, sunlight, nourishment, and other natural resources disproportionately, depriving native species of all available resources. They reproduce quickly and consistently, replacing native creatures. There has been transportation of species, consciously or unknowingly, since the geographical voyages, mainly during the 17th and 19th centuries. Many animals and birds migrate as a natural part of their life cycle, driven by physiological needs and environmental changes. This natural migration is not a factor in species introduction, which is mostly due to human activity. One of the major causes of biodiversity loss is biological invasions. As biological invasion threats grow, identifying high-vulnerability locations is becoming increasingly important. Biological invasions continue to have a significant negative influence on the environment and the economy. It's vital to understand why some introduced species become invasive before they can be managed. The ecology and physiology of the species in the invaded range have been studied in order to determine the processes underlying invasion success. However, a rising corpus of research highlighting insights derived from investigating invasion success as a biogeographic issue is highlighting the use of biogeographic techniques. Invaders have the ability to drastically alter the species composition and function of native ecosystems through competition, predation, and habitat disruption. Biological invasions have a significant economic impact on the world economy, with annual costs in the United States alone estimated at over $100 billion. Invasions occur when organisms are introduced outside of their native or historic range, either purposefully or unintentionally, and then spread effectively in their new surroundings. Exotic species, which include cattle, crops, and garden plants, are any species that isn't native to a specific location. Biological invaders are non-native creatures that spread outside of an ecosystem dominated by humans. The distinguishing characteristics of invasions, such as some marine species, plant species, and animals, are some remarkable instances. In addition, we document the biogeographic distribution of invasive species, as well as the diversity of species, habitats, and climate zones studied. A fact study and prediction analysis of key records and data related to our research aim were included in our research, which let us come to a decision on the obstacles, potential difficulties and future prospects of "Biogeography and Invasion Biology- A Theoretical Study."

The Novel Concept of Synergically Combining: High Hydrostatic Pressure and Lytic Bacteriophages to Eliminate Vegetative and Spore-Forming Bacteria in Food Products.

The article focuses on the ongoing challenge of eliminating vegetative and spore-forming bacteria from food products that exhibit resistance to the traditional preservation methods. In response to this need, the authors highlight an innovative approach based on the synergistic utilization of high-hydrostatic-pressure (HHP) and lytic bacteriophages. The article reviews the current research on the use of HHP and lytic bacteriophages to combat bacteria in food products. The scope includes a comprehensive review of the existing literature on bacterial cell damage following HHP application, aiming to elucidate the synergistic effects of these technologies. Through this in-depth analysis, the article aims to contribute to a deeper understanding of how these innovative techniques can improve food safety and quality. There is no available research on the use of HHP and bacteriophages in the elimination of spore-forming bacteria; however, an important role of the synergistic effect of HHP and lytic bacteriophages with the appropriate adjustment of the parameters has been demonstrated in the more effective elimination of non-spore-forming bacteria from food products. This suggests that, when using this approach in the case of spore-forming bacteria, there is a high chance of the effective inactivation of this biological threat.

Inactivated rabies-based Lassa fever virus vaccine candidate LASSARAB protects nonhuman primates from lethal disease

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization’s (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to serve as a negative control. NHPs immunized with LASSARAB developed strong humoral responses to LASV-GPC. Upon challenge, NHPs vaccinated with LASSARAB survived to the study endpoint, whereas NHPs in the control group did not. This study demonstrates that LASSARAB is a worthy candidate for continued development.

Data sharing considerations to maximize the use of pathogen biological and genomics resources data for public health.

Public sector data associated with health are a highly valuable resource with multiple potential end-users, from health practitioners, researchers, public bodies, policy makers, and industry. Data for infectious disease agents are used for epidemiological investigations, disease tracking and assessing emerging biological threats. Yet, there are challenges in collating and re-using it. Data may be derived from multiple sources, generated and collected for different purposes. While public sector data should be open access, providers from public health settings or from agriculture, food, or environment sources have sensitivity criteria to meet with ethical restrictions in how the data can be reused. Yet, sharable datasets need to describe the pathogens with sufficient contextual metadata for maximal utility, e.g. associated disease or disease potential and the pathogen source. As data comprise the physical resources of pathogen collections and potentially associated sequences, there is an added emerging technical issue of integration of omics 'big data'. Thus, there is a need to identify suitable means to integrate and safely access diverse data for pathogens. Established genomics alliances and platforms interpret and meet the challenges in different ways depending on their own context. Nonetheless, their templates and frameworks provide a solution for adaption to pathogen datasets.

Rapid, Simultaneous Detection of Various Biological Toxin Genes Using Multiplex Reverse Transcription Loop-Mediated Isothermal Amplification(RT-LAMP)

Rapid, early, accurate detection and identification of the various pathogenic agents associated with the development of biological weapons is critical in preventing loss of life and limiting the impact of these organisms when used against civilian or military targets. The aim of this study was to produce a system for the simple, rapid, accurate and simultaneous detection and identification of Ricin, Botulinum toxin B and Staphylococcal enterotoxin B as a proof of principle for developing field appropriate reverse transcription loop-mediated isothermal amplification systems for the accurate identification of potential biological threats. These systems were designed to facilitate the identification of potential threats even in remote or resource-limited locations.

Insights into the effects of anilofos on direct-seeded rice production system through untargeted metabolomics

Insights into the effects of anilofos on direct-seeded rice production system through untargeted metabolomics

A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body. How the body senses this glucose loss and consequently enhances glucose production is unclear. Using renal Slc2a2 (also known as Glut2) knockout mice, we demonstrate that elevated glycosuria activates the hypothalamic-pituitary-adrenal axis, which in turn drives endogenous glucose production. This phenotype was attenuated by selective afferent renal denervation, indicating the involvement of the afferent nerves in promoting the compensatory increase in glucose production. In addition, through plasma proteomics analyses we observed that acute phase proteins - which are usually involved in the body’s defense mechanisms against a threat – were the top candidates which were either upregulated or downregulated in renal Slc2a2 KO mice. Overall, afferent renal nerves contribute to promoting endogenous glucose production in response to elevated glycosuria and loss of glucose in urine is sensed as a biological threat in mice. These findings may be useful in improving the efficiency of drugs like SGLT2 inhibitors that are intended to treat hyperglycemia by enhancing glycosuria but are met with a compensatory increase in endogenous glucose production.

A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body. How the body senses this glucose loss and consequently enhances glucose production is unclear. Using renal Slc2a2 (also known as Glut2) knockout mice, we demonstrate that elevated glycosuria activates the hypothalamic-pituitary-adrenal axis, which in turn drives endogenous glucose production. This phenotype was attenuated by selective afferent renal denervation, indicating the involvement of the afferent nerves in promoting the compensatory increase in glucose production. In addition, through plasma proteomics analyses we observed that acute phase proteins - which are usually involved in the body's defense mechanisms against a threat - were the top candidates which were either upregulated or downregulated in renal Slc2a2 KO mice. Overall, afferent renal nerves contribute to promoting endogenous glucose production in response to elevated glycosuria and loss of glucose in urine is sensed as a biological threat in mice. These findings may be useful in improving the efficiency of drugs like SGLT2 inhibitors that are intended to treat hyperglycemia by enhancing glycosuria but are met with a compensatory increase in endogenous glucose production.