Basic Physiological Functions Research Articles

Adverse Effects of Aβ1-42 Oligomers: Impaired Contextual Memory and Altered Intrinsic Properties of CA1 Pyramidal Neurons

Aβ1-42 (amyloid beta) oligomers, the major neurotoxic culprits in Alzheimer’s disease, initiate early pathophysiological events, including neuronal hyperactivity, that underlie aberrant network activity and cognitive impairment. Although several synaptotoxic effects have been extensively studied, neuronal hyperexcitability, which may also contribute to cognitive deficits, is not fully understood. Here, we found several adverse effects of in vivo injection of Aβ1-42 oligomers on contextual memory and intrinsic properties of CA1 pyramidal neurons. Male rats underwent behavioral and electrophysiological studies 1 week after microinjections into the dorsal CA1 region, followed by histological analysis. After 1 week, Aβ1-42 oligomers impaired contextual learning without affecting basic physiological functions and triggered training-induced neuronal excitability. Furthermore, riluzole, a persistent sodium current (INaP) blocker, dose-dependently reduced Aβ1-42 oligomer-induced hyperexcitability. Congo red staining, which detects insoluble amyloid deposits, further identified labeling of CA1 pyramidal neurons while immunohistochemistry with lecanemab, which detects soluble Aβ oligomers, revealed immunoreactivity of both pyramidal and non-pyramidal cells in the target area. Therefore, our study suggests that a single injection of Aβ1-42 oligomers resulted in contextual memory deficits along with concomitant neuronal hyperexcitability and amyloid deposition in the CA1 region after 1 week.

Systematic Insights into the Relationship between the Microbiota-Gut-Brain Axis and Stroke with the Focus on Tryptophan Metabolism.

Stroke, as a serious cerebral vascular disease with high incidence and high rates of disability and mortality, has limited therapeutic options due to the narrow time window. Compelling evidence has highlighted the significance of the gut microbiota and gut-brain axis as critical regulatory factors affecting stroke. Along the microbiota-gut-brain axis, tryptophan metabolism further acquires increasing attention for its intimate association with central nervous system diseases. For the purpose of exploring the potential role of tryptophan metabolism in stroke and providing systematic insights into the intricate connection of the microbiota-gut-brain axis with the pathological procedure of stroke, this review first summarized the practical relationship between microbiota and stroke by compiling the latest case-control research. Then, the microbiota-gut-brain axis, as well as its interaction with stroke, were comprehensively elucidated on the basis of the basic anatomical structure and physiological function. Based on the crosstalk of microbiota-gut-brain, we further focused on the tryptophan metabolism from the three major metabolic pathways, namely, the kynurenine pathway, serotonin pathway, and microbial pathway, within the axis. Moreover, the effects of tryptophan metabolism on stroke were appreciated and elaborated here, which is scarcely found in other reviews. Hopefully, the systematic illustration of the mechanisms and pathways along the microbiota-gut-brain axis will inspire more translational research from metabolic perspectives, along with more attention paid to tryptophan metabolism as a promising pharmaceutical target in order to reduce the risk of stroke, mitigate the stroke progression, and ameliorate the stroke prognosis.

Dynamics of the content of immunoglobulin classes in blood serum and vaginal secretions of cows with genital mycoplasmosis with various methods of therapy

The economic efficiency of industrial animal husbandry in modern conditions provides not only for an increase in productivity, but also for maintaining the optimal level of basic physiological functions, including reproductive ones. The successful implementation of the task of preserving reproductive function is hindered by diseases of females of various etiologies that negatively affect their reproductive ability. One of these diseases is genital mycoplasmosis of cattle, which has a significant prevalence on dairy farms, both abroad and in the Russian Federation. The effectiveness of therapy for this disease largely depends on the initial state of the immune system. The objective of our research was to study the therapeutic efficacy and effect on the immunoglobulin composition of blood serum and vaginal secretions of patients with genital mycoplasmosis of cows of the use of the antibiotic tulathromycin and its combination with the immunomodulator thymalin. The results obtained demonstrated that the use of tulatromycin for treatment leads to the recovery of 75% of experimental animals and ensures the restoration of the immunoglobulin profile of vaginal secretions, whereas the immunodeficiency state observed in blood serum is only partially restored. The combination of an antibiotic and an immunomodulator ensured the recovery of all experimental animals and the restoration of the immunological characteristics of blood serum and vaginal secretions to the level of healthy cows.

Alcohol use and the pain system.

The World Health Organization's epidemiological data from 2016 revealed that while 57% of the global population aged 15years or older had abstained from drinking alcohol in the previous year, more than half of the population in the Americas, Europe, and Western Pacific consumed alcohol. The spectrum of alcohol use behavior is broad: low-risk use (sensible and in moderation), at-risk use (e.g., binge drinking), harmful use (misuse) and dependence (alcoholism; addiction; alcohol use disorder). The at-risk use and misuse of alcohol is associated with the transition to dependence, as well as many damaging health outcomes and preventable causes of premature death. Recent conceptualizations of alcohol dependence posit that the subjective experience of pain may be a significant contributing factor in the transition across the spectrum of alcohol use behavior. This narrative review summarizes the effects of alcohol at all levels of the pain system. The pain system includes nociceptors as sensory indicators of potentially dangerous stimuli and tissue damage (nociception), spinal circuits mediating defensive reflexes, and most importantly, the supraspinal circuits mediating nocifensive behaviors and the perception of pain. Although the functional importance of pain is to protect from injury and further or future damage, chronic pain may emerge despite the recovery from, and absence of, biological damage (i.e., in the absence of nociception). Like other biological perceptual systems, pain is a construction contingent on sensory information and a history of individual experiences (i.e., learning and memory). Neuroadaptations and brain plasticity underlying learning and memory and other basic physiological functions can also result in pathological conditions such as chronic pain and addiction. Moreover, the negative affective/emotional aspect of pain perception provides embodied and motivational components that may play a substantial role in the transition from alcohol use to dependence.

Meko podlaganje imedijatne totalne proteze - prikaz slučaja

Introduction: With the placement of dental implants in edentulous patients, creating and adapting immediate dentures is crucial to allow patients to perform basic physiological functions during the osseointegration period without affecting implant healing. This report presents a case of direct soft lining of immediate complete dentures following implant placement. Case Report: Six dental implants were inserted in the upper jaw, while the patient retained natural teeth in the lower jaw. An immediate complete denture was fabricated and adjusted for the upper jaw. The prosthesis base was prepared and processed to accommodate soft lining material. Adhesive was applied to the prepared base, followed by silicone application for soft fitting onto the prosthesis base, which was then inserted into the patient's mouth. After three minutes, the denture was removed, and soft lining treatment of the immediate complete denture was completed. Conclusion: Direct soft lining facilitated patient adaptation to the immediate prosthesis and supported safer healing and osseointegration until definitive work could be completed. The addition of a soft silicone layer reduced pressure on the residual alveolar ridge and improved adhesion of the immediate prosthesis.

Comparison of the antibiotic resistance mechanisms in a gram-positive and a gram-negative bacterium by gene networks analysis.

Nowadays, the emergence of some microbial species resistant to antibiotics, both gram-positive and gram-negative bacteria, is due to changes in molecular activities, biological processes and their cellular structure in order to survive. The aim of the gene network analysis for the drug-resistant Enterococcus faecium as gram-positive and Salmonella Typhimurium as gram-negative bacteria was to gain insights into the important interactions between hub genes involved in key molecular pathways associated with cellular adaptations and the comparison of survival mechanisms of these two bacteria exposed to ciprofloxacin. To identify the gene clusters and hub genes, the gene networks in drug-resistant E. faecium and S. Typhimurium were analyzed using Cytoscape. Subsequently, the putative regulatory elements were found by examining the promoter regions of the hub genes and their gene ontology (GO) was determined. In addition, the interaction between milRNAs and up-regulated genes was predicted. RcsC and D920_01853 have been identified as the most important of the hub genes in S. Typhimurium and E. faecium, respectively. The enrichment analysis of hub genes revealed the importance of efflux pumps, and different enzymatic and binding activities in both bacteria. However, E. faecium specifically increases phospholipid biosynthesis and isopentenyl diphosphate biosynthesis, whereas S. Typhimurium focuses on phosphorelay signal transduction, transcriptional regulation, and protein autophosphorylation. The similarities in the GO findings of the promoters suggest common pathways for survival and basic physiological functions of both bacteria, including peptidoglycan production, glucose transport and cellular homeostasis. The genes with the most interactions with milRNAs include dpiB, rcsC and kdpD in S. Typhimurium and EFAU004_01228, EFAU004_02016 and EFAU004_00870 in E. faecium, respectively. The results showed that gram-positive and gram-negative bacteria have different mechanisms to survive under antibiotic stress. By deciphering their intricate adaptations, we can develop more effective therapeutic approaches and combat the challenges posed by multidrug-resistant bacteria.

In vitro evaluation of exocytosis-associated SNARE molecules in human granulosa cells in polycystic ovary syndrome.

Patients with polycystic ovarian morphology (PCOM) make up 20% cases forassisted reproductive technology (ART). Folliculogenesis is impaired in PCOS. Signaling molecules are involved in follicle development. Dysregulations of intrafollicular environment and signaling molecules are observed in PCOS. Granulosa cells (GCs) and oocytes secrete molecules into follicular fluid by exocytosis of SNAREs. The aim of this study is to evaluate vesicle transport and vesicle fusion proteins (SNAREs) in GCs from PCOS patients who have undergone IVF treatment. Follicular fluids were collected from patients who undergo IVF/ICSI with the diagnosis of male factor (n = 10) and PCOS (n = 10) patients. GCs were separated and cultured. Each group of GCs was stimulated with FSH-hCG. The cells were examined under electron microscope. Immunofluorescent labeling was performed on cells for Stx6, SNAP25, StxBP1, FSHr, and KITL. Integrated density was analyzed from images of Stx6, SNAP25, StxBP1, FSHr, and KITL. Intercellular communication occurs by signal molecules; Stx6, SNAP25, and StxBP1 fusion proteins involved in exocytosis were decreased in the GCs of PCOS. There was no increase in in vitro stimulation with FSH-hCG either. In the electron microscope, it was observed that exocytosis of the vesicles was disrupted. Exocytosis and vesicular dynamics are among the basic physiological functions of human steroidogenic granulosa cells. Follicle development is necessary for production of competentoocytes and ovulation. Understanding the pathophysiology of PCOS at follicular level is important for diseasemanagement. According to our findings, deficits in vesicular dynamics of human granulosa cells in may be central to the treatment strategy forPCOS patients.

Soluble adenylyl cyclase, the cell-autonomous member of the family

Soluble adenylyl cyclase (sAC) is the evolutionarily most ancient of a set of 10 adenylyl cyclases (Adcys). While Adcy1 to Adcy9 are cAMP-producing enzymes that are activated by G-protein coupled receptors (GPCRs), Adcy10 (sAC) is an intracellular adenylyl cyclase. sAC plays a pivotal role in numerous cellular processes, ranging from basic physiological functions to complex signaling cascades. As a distinct member of the adenylyl cyclase family, sAC is not activated by GPCRs and stands apart due to its unique characteristics, regulation, and localization within cells. This minireview aims to honour Ulli Brandt, the outgoing Executive Editor of our journal, Biochimica Biophysica Acta (BBA), and longstanding Executive Editor of the BBA section Bioenergetics. We will therefore focus this review on bioenergetic aspects of sAC and, in addition, review some important recent general developments in the field of research on sAC.

Comparative biology and non-traditional approaches for basic aging research for facilitating translational studies.

As humans, we aspire to healthy aging and ideally reaching our maximal lifespan. That, however, requires optimizing resilience to stressors and minimizing exposure to factors that accelerate aging. Understanding the complexities of aging processes involves characterizing the causal bases of physical, physiological, and cognitive deficits that accumulate over time, eventually culminating in reduced functionality and decreased resistance to disease and environmental stressors. Both the progression of age-related conditions and onset of diseases are affected by environmental stressors; however, the basis for increased susceptibility remains poorly understood. Furthermore, the actions of some environmental stressors, such as endocrine disruptors, can alter both developmental and aging processes, contributing to lifelong issues with inflammatory and neurodegenerative conditions. This manuscript focuses on the comparative biology and evolution of aging and longevity. The status of an array of animal models and potential for specific geroscience translational applications is addressed by asking these questions. What animal models are currently available for aging and translational geroscience? What are the key roadblocks and barriers for studies of healthy aging, and how might specific animal models be useful? Are research tools available? Which vertebrate animal models can specifically address targeted questions in human aging processes? Can information be synthesized for a range of vertebrate species to identify suitable animal models for addressing specific research questions in geroscience, especially relative to basic physiological function, timing and trajectory of disease progression, effects of environmental stressors, and potential for regenerative medicine?

La réhabilitation psychosociale en addictologie

ObjectivesAddictive behaviors constitute complex behaviors that are usually related to social habits, such as substance use, gambling or gaming activities, or sexual or physical activity. They progressively overrun and stifle the routine habits of the concerned individuals, for example within their occupational or family spheres of life, as well as in their hobbies or in their main physiological functions, such as sleep or eating cycles. The rehabilitation approach of care integrates the objective of restoring the altered habits and functional rhythms, to optimize the clinical outcomes and improve quality of life of the concerned persons. MethodsUsing a focused and narrative literature review, we aimed to explain what psychosocial rehabilitation consists in, and why this approach is particularly relevant for the addiction care, although to date it has remained insufficiently developed in the routine practice of many facilities. ResultsThe “rehab” approach, is first based on a structured and comprehensive assessment of the clinical and functional aspects of the patient, which secondarily allows to frame an individualized project of care that is closely built together with the patient. This project of care can integrate classical pharmacotherapeutic and psychotherapeutic tools, but it also emphasizes wider approaches for restoring some basic social and physiological functions of the concerned person, such as sleep, eating, social functioning, physical activity, or spiritual needs. Priorities among these different dimensions have to be defined by the concerned person. ConclusionsThe “rehab” approach is particularly relevant in addiction medicine. It represents a more global conception of care that conceives the recovery of social and physiological functioning as a core treatment objective for the concerned persons. The consequences for care organization are that many additional professionals should be integrated into the treatment schemes for addiction, including peer counselors, occupational therapists, physical activity coaches, or dieticians.

In vivo and In vitro Model for Evaluation of Anti-microbial activity: A Review

The rates of infectious diseases have significantly increased in recent years. So need for production, evaluation and standardization of new antimicrobial agents has also increased. The major problem of resistance towards antibacterial, antiviral, etc drugs is also posing a great threat to human beings as many bacteria, viruses and fungi have become resistant to commonly used drugs. However, microbes are also useful for us in our basic physiological functions, for example: digestion, so we also need to make sure the new molecules of antimicrobials do not cause harm to our natural microbial flora. In this review, we have tried to assemble some In-Vivo and In-vitro Model for evaluating Antimicrobial agents. Classifications of antibacterials, antivirals and antifungals have been displayed in an easy way. The use of herbal drugs is displayed in a tabular manner and finally the evaluation parameters have been discussed.

Classical and Non-Classical Neural Communications

This review was constructed to show how the connectome has evolved in motor command systems from simple command elements to complex systems of neurons utilizing parallel distributed processing and the possibility of quantum entanglement between groups of neurons. Scientific and medical interest in neural pathways and their connections have driven neuroscience and brain research for many decades so that specific systems and their feedback loops have been considered in detail. We review motor command systems in invertebrate and vertebrate nervous systems, using PubMed and more generalized searches. We contemplate the attractiveness of the command neuron concept and why it has been largely superseded by parallel distributed processing (PDP) in both vertebrate and invertebrate models. Action potentials, synaptic connectivity and communication within the nervous system are extremely important to understanding basic neurological and physiological functions. However, newer concepts suggest computation within nervous systems may resemble quantum phase computation and that computational action potentials are also quantal. We suggest that a rational form of computation that can operate according to the physiological constraints of neurons and their connectivity is essential in further evaluating neuronal interactions. We also consider recent studies that indicate that quantum entanglement may occur in the human brain. Thus some brain functions may be non-classical, most likely the phenomena of consciousness and self-awareness. The significance of this review is that future studies on motor command should not just consider the connectome but should also consider computational systems within nervous systems and the likelihood of quantum entanglement between groups of neurons not currently indicated by the connectome.

Pleiotropic Signaling by Reactive Oxygen Species Concerted with Dietary Phytochemicals and Microbial-Derived Metabolites as Potent Therapeutic Regulators of the Tumor Microenvironment.

The excessive generation of reactive oxygen species (ROS) plays a pivotal role in the pathogenesis of diseases. ROS are central to cellular redox regulation and act as second messengers to activate redox-sensitive signals. Recent studies have revealed that certain sources of ROS can be beneficial or harmful to human health. Considering the essential and pleiotropic roles of ROS in basic physiological functions, future therapeutics should be designed to modulate the redox state. Dietary phytochemicals, microbiota, and metabolites derived from them can be expected to be developed as drugs to prevent or treat disorders in the tumor microenvironment.

Microbiome, immune system and cancer: three sides of the one medal

Purpose of the study to analyze current ideas about the relationship between the microbiota (microbiome) and the human body in the aspect of cancer pathogenesis, ambivalent character of these interactions, and the role of the immune system and immunoinfammatory status that promotes carcinogenesis or prevents neoplastic processes.Material and Methods. Literature search was carried out using Medline, Cochrane Library, Elibrary and PubMed systems, including publications over the last 7 years.Results. The microbiota includes all communities of commensal, symbiotic, and pathogenic microorganisms: bacteria, fungi, archaea, and viruses that colonize the gastrointestinal tract and other organs and tissues. The microbiome is an important factor in cancer pathogenesis due to its involvement in the basic physiological functions of the host, such as digestion, development of the immune system, and modulation of endocrine functions. In the review, the influence of microbiota of different locations (gastrointestinal tract, breast, intravaginal tract) on the development and progression of breast, colorectal and cervical cancers was discussed. The role of the microbiome in cancer pathogenesis is realized by the participation in neoplastic transformation of the epithelium, regulation of tumor progression under conditions of manifested malignant process, and modifcation of the therapeutic effect of standard drugs, including the development of original probiotic-based anticancer agents. The study of the mechanisms of action of the microbiome in the host organism opens up prospects for the development of new approaches to cancer therapy. Particular attention was paid to the mechanisms of the immunomodulatory effect of the microbiota in terms of reducing the risk of malignancy, regulating tumor progression and participating in antitumor therapy. The clinical significance of determining pathogenetically significant microbial markers associated with the aggressive form of cancer, response to treatment and toxicity of therapy was discussed. Particular attention should be paid to the potential mechanisms of interaction between cancer – microbiome – probiotics, since the latter can provide modification of malignancy processes, exert an antitumor effect, and modulate the effectiveness of drug therapy. The feasibility of editing the microbiota by probiotics was considered, and antitumor properties (effects) of bacteria and strategies for modifying the microbiome for the prevention and treatment of cancer were discussed.

What does not kill it makes it stronger! The tolerance of the F1 larvae of Chironomus xanthus to a neonicotinoid insecticide formulation

Thiamethoxam (TMX) is a systemic neonicotinoid that acts as a partial agonist of the nicotinic acetylcholine receptors (nAChRs). However, target species have shown resistance to formulations based on such neonicotinoids, which can also be expected for non-target insects. This research aimed to study the effects of a formulation based on TMX [Cruiser® 350 FS (CRZ)] on the life traits of Chironomus xanthus filial generation (F1) and compare it with the parental generation (P). Environmentally relevant concentrations of CRZ significantly decreased larvae growth P generation , also slowing and decreasing their emergence. Larvae of the F1 generation were less sensitive than their parents, suggesting that the progeny were able to thrive and perform basic physiological functions better than the parental generation. Our results highlight that insect resistance to neonicotinoids may be associated with the better performance of the filial generation, which is related to the change in affinities of the active ingredient for the sub-units constituting the nAChRs subtypes of F1 organisms, inherited from P organisms that were able to survive and reproduce. Moreover, further studies using biochemical and omics tools should be performed to disentangle the specific changes occurring at the nAChRs throughout insect development.

Organ Chips and Visualization of Biological Systems.

Organ-on-a-chip (OOC) is an emerging frontier cross-cutting science and technology developed in the past 10 years. It was first proposed by the Wyss Institute for Biologically Inspired Engineering of Harvard Medical School. It consists of a transparent flexible polymer the size of a computer memory stick, with hollow microfluidic channels lined with living human cells. Researchers used bionics methods to simulate the microenvironment of human cells on microfluidic chips, so as to realize the basic physiological functions of corresponding tissues and organs in vitro. Transparent chip materials can perform real-time visualization and high-resolution analysis of various human life processes in a way that is impossible in animal models, so as to better reproduce the microenvironment of human tissue and simulate biological systems in vitro to observe drug metabolism and other life processes. It provides innovative research systems and system solutions for in vitro bionics of biological systems. It also has gradually become a new tool for disease mechanism research and new drug development. In this chapter, we will take the current research mature single-organ-on-a-chip and multi-organ human-on-a-chip as examples; give an overview of the research background and underlying technologies in this field, especially the application of in vitro bionic models in visualized medicine; and look forward to the foreseeable future development prospects after the integration of organ-on-chip and organoid technology.

The role of interaction between autophagy and apoptosis in tumorigenesis (Review).

Autophagy is a highly conserved process that maintains cellular homeostasis during evolution. Autophagy can occur in the form of macroautophagy, microautophagy or molecular chaperone autophagy, among which macroautophagy is the most common. Apoptosis exists in all kinds of cell organisms, and is a kind of programmed cell death which is regulated by pro-apoptotic factors and anti-apoptotic signals. The main biological feature of apoptosis is the activation of caspase. Apoptosis is induced by a variety of cell signals, such as endoplasmic reticulum stress, induction of toxic substances, stimulation of pathogenic microorganisms and DNA damage. Inextricable links are found between autophagy and apoptosis. Studies have found that numerous of the autophagy molecules and autophagy signaling pathways involved in the process of autophagy are related to apoptosis. In addition to regulating autophagy, the autophagy signaling pathway also regulates apoptosis. The interaction between the two can achieve a dynamic balance to certain extent, which maintains the basic physiological functions of cells and reduces the damage to the body under stress. Disease occurs when the balance between autophagy and apoptosis is disrupted. Tumors form due to the ability of cells to avoid apoptosis. Autophagy is closely related to apoptosis, there must be a close connection between the three. In the present review, the mechanism between autophagy and apoptosis and the impact of their interaction on tumorigenesis shall be discussed.

The past and future of transient receptor potential: A scientometric analysis.

Background:Thermoreceptors include TRPV1 and TRPM8. TRPV1 and TRPM8 are TRP channels. TRP ion channels are widely expressed in many different tissues and cell types, and are involved in different physiological processes. Research on the structure and basic physiological functions of TRPV1 is relatively perfect, and the relationship between the pathogenesis of other members of the TRP family and specific diseases and TRPV1 remains to be explored in depth.Methods:Articles regarding TRP were culled from the Web of Science Core Collection, and knowledge maps were generated using the CiteSpace software.Results:In total, 19,862 articles were included. The number of published articles on this topic has rapidly increased since 2000, with more than 1000 articles published per year by 2020. MAKOTO TOMINAGA was the author with the most articles. The countries with the most articles were the United States and China. However, the number of articles in the U.S. was 3 times that in China. The organizations that publish the most articles are Harvard University in the US and Seoul Natl University in South Korea. TRP and the pathogenesis of diseases, such as neuropathy and stroke, are hotspots of current research.Conclusion:To our knowledge, this is the first study to provide an overview of the literature on TRP. Research on TRPs is developing rapidly.

Evaluation of Septoria leaf spot (Septoria helianthi) alone and in combination with other foliar fungal spots on sunflower

Abstract In recent years, Septoria leaf spot has taken a strong place in the list of economically important diseases of sunflower. It may be a favorable factor for the development of other diseases on sunflower plants too. The aim of the research was to evaluate the frequency and degree of infection of sunflower plants with Septoria helianthi as well as possibility of simultaneous infection with this pathogen and other fungi which cause foliar spots, such as downy mildew, Alternaria leaf spot and Phoma black stem under conditions of stationary infectious nursery. The year 2021 turned out to be extremely favorable for the development of fungal leaf spots on sunflower. Assessment of fungal diseases of sunflower plants was performed in F2 families obtained after crossing ZL22A, ZL58A, ZL70A, ZL78A, and ZL169A lines of Zaporozhye breeding (Ukraine) with HAR7 line (originating from the USA). Each F2 family (sample) was obtained from self-pollination of one F1 plant with varying severity of Septoria disease. It was found that in the conditions of 2021, sunflower was quite affected by Septoria disease. The percentage of injured plants in F2 samples ranged from 41.0 to 100.0%. The severity of disease was different. Less resistant genotypes included plants with lesions on sunflower leaves of lower, middle, and upper tiers in approximately equal numbers, while more resistant genotypes had almost no plants with injured leaves of upper tiers. It was established that the development of Phoma disease occurred both on plants with Septoria leaf spot and on healthy plants. On average, among the plants infected with Phoma macdonaldii, the proportion of plants jointly affected by Phoma and Septoria diseases was 2/3. However, the frequency of simultaneous infection of plants with S. helianthi and P. macdonaldii in genotypes with different resistance to Septoria leaf spot differed significantly and ranged from 80% in less resistant to 40% in more resistant accessions. Most plants (about 90%) infected with Plasmopara halstedii were simultaneously infected with S. helianthi. That is, both of these pathogens can simultaneously develop on the same plant and lead to a decline in its basic physiological functions. The rate of simultaneous damage of sunflower by Alternaria and Septoria was quite low compared to plant damage by Alternaria alone and was less than 30%. This may mean that the pathogen of Alternaria leaf spot avoids plants with existing S. helianthi fungus.

Chronic Loss of Muscarinic M5 Receptor Function Manifests Disparate Impairments in Exploratory Behavior in Male and Female Mice despite Common Dopamine Regulation.

There are five cloned muscarinic acetylcholine receptors (M1-M5). Of these, the muscarinic type 5 receptor (M5) is the only one localized to dopamine neurons in the ventral tegmental area and substantia nigra. Unlike M1-M4, the M5 receptor has relatively restricted expression in the brain, making it an attractive therapeutic target. Here, we performed an in-depth characterization of M5-dependent potentiation of dopamine transmission in the nucleus accumbens and accompanying exploratory behaviors in male and female mice. We show that M5 receptors potentiate dopamine transmission by acting directly on the terminals within the nucleus accumbens. Using the muscarinic agonist oxotremorine, we revealed a unique concentration-response curve and a sensitivity to repeated forced swim stress or restraint stress exposure. We found that constitutive deletion of M5 receptors reduced exploration of the center of an open field while at the same time impairing normal habituation only in male mice. In addition, M5 deletion reduced exploration of salient stimuli, especially under conditions of high novelty, yet had no effect on hedonia assayed using the sucrose preference test or on stress-coping strategy assayed using the forced swim test. We conclude that M5 receptors are critical for both engaging with the environment and updating behavioral output in response to environment cues, specifically in male mice. A cardinal feature of mood and anxiety disorders is withdrawal from the environment. These data indicate that boosting M5 receptor activity may be a useful therapeutic target for ameliorating these symptoms of depression and anxiety.SIGNIFICANCE STATEMENT The basic physiological and behavioral functions of the muscarinic M5 receptor remain understudied. Furthermore, its presence on dopamine neurons, relatively restricted expression in the brain, and recent crystallization make it an attractive target for therapeutic development. Yet, most preclinical studies of M5 receptor function have primarily focused on substance use disorders in male rodents. Here, we characterized the role of M5 receptors in potentiating dopamine transmission in the nucleus accumbens, finding impaired functioning after stress exposure. Furthermore, we show that M5 receptors can modulate exploratory behavior in a sex-specific manner, without affecting hedonic behavior. These findings further illustrate the therapeutic potential of the M5 receptor, warranting further research in the context of treating mood disorders.