Intracellular Signaling Systems Research Articles

Using the Strategy of Genome-Wide Association Studies to Identify Genetic Markers of Suicidal Behavior: A Narrative Review.

Several studies involving various suicidal phenotypes based on the strategy of the search of genome-wide associations with single nucleotide polymorphisms have been performed recently. These studies need to be generalized. To systematize the findings of a number of genome-wide association studies (GWAS) for suicidal phenotypes, annotate the identified markers, analyze their functionality, and possibly substantiate the hypothesis holding that these phenotypes reflect a nonspecific set of gene variants that are relevant as relates to stress-vulnerability as a key endophenotype of suicidal behavior (SB). A search on the PubMed and related resources using the combinations "suicide AND GWAS" and "suicidal behavior AND GWAS" was performed. It yielded a total of 34 independent studies and meta-analyses. For the 10 years since such studies emerged, they have undergone significant progress. Estimates of the SNP heritability of SB in some cases are comparable with estimates of heritability based on the twin method. Many studies show a high genetic correlation with the genomic markers of the most common mental disorders (depression, bipolar disorder, schizophrenia, post-traumatic stress disorder). At the same time, a genomic architecture specific to SB is also encountered. Studies utilizing the GWAS strategy have not revealed any associations of SB with candidate genes that had been previously studied in detail (different neurotransmitters, stress response system, polyamines, etc.). Frequently reported findings from various studies belong in three main groups: 1) genes involved in cell interactions, neurogenesis, the development of brain structures, inflammation, and the immune responses; 2) genes encoding receptors for neurotrophins and various components of the intracellular signaling systems involved in synaptic plasticity, embryonic development, and carcinogenesis; and 3) genes encoding various neuro-specific proteins and regulators. In general, GWAS in the field of suicidology mainly serve the purpose of a deeper understanding of the pathophysiology of suicidal behavior. However, they also demonstrate growing capability in terms of predicting and preventing suicide, especially when calculating the polygenic risk score among certain populations (psychiatric patients) and in combination with tests of different modalities. From our point of view, there exists a set of markers revealed by the GWAS strategy that seems to point to a leading role played by stress vulnerability, an endophenotype that is formed during early development and which subsequently comes to play the role of key pathogenetic mechanism in SB.

The DEP1 Mutation Improves Stem Lodging Resistance and Biomass Saccharification by Affecting Cell Wall Biosynthesis in Rice

BackgroundPlant cell walls have evolved precise plasticity in response to environmental stimuli. The plant heterotrimeric G protein complexes could sense and transmit extracellular signals to intracellular signaling systems, and activate a series of downstream responses. dep1 (Dense and Erect Panicles 1), the gain-of-function mutation of DEP1 encoding a G protein γ subunit, confers rice multiple improved agronomic traits. However, the effects of DEP1 on cell wall biosynthesis and wall-related agronomic traits remain largely unknown.ResultsIn this study, we showed that the DEP1 mutation affects cell wall biosynthesis, leading to improved lodging resistance and biomass saccharification. The DEP1 is ubiquitously expressed with a relatively higher expression level in tissues rich in cell walls. The CRISPR/Cas9 editing mutants of DEP1 (dep1-cs) displayed a significant enhancement in stem mechanical properties relative to the wild-type, leading to a substantial improvement in lodging resistance. Cell wall analyses showed that the DEP1 mutation increased the contents of cellulose, hemicelluloses, and pectin, and reduced lignin content and cellulose crystallinity (CrI). Additionally, the dep1-cs seedlings exhibited higher sensitivity to cellulose biosynthesis inhibitors, 2,6-Dichlorobenzonitrile (DCB) and isoxaben, compared with the wild-type, confirming the role of DEP1 in cellulose deposition. Moreover, the DEP1 mutation-mediated alterations of cell walls lead to increased enzymatic saccharification of biomass after the alkali pretreatment. Furthermore, the comparative transcriptome analysis revealed that the DEP1 mutation substantially altered expression of genes involved in carbohydrate metabolism, and cell wall biosynthesis.ConclusionsOur findings revealed the roles of DEP1 in cell wall biosynthesis, lodging resistance, and biomass saccharification in rice and suggested genetic modification of DEP1 as a potential strategy to develop energy rice varieties with high lodging resistance.

Mitochondrial Dysfunction as the Major Basis of Brain Aging.

The changes in the properties of three biological events that occur with cerebral aging are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by the mitochondria in the transition of these three important processes toward more deleterious variants as brain aging proceeds. The immune system: the shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. Reactive oxygen species are important intracellular signaling systems. Additionally, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted, and persistent generation of pro-oxidant free radicals (oxidative stress). The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffused. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex.

Breathing behaviour involves the generation of normal breaths (eupnoea) on a timescale of seconds and sigh breaths on the order of minutes. Both rhythms emerge in tandem from a single brainstem site, but whether and how a single cell population can generate two disparate rhythms remains unclear. We posit that recurrent synaptic excitation in concert with synaptic depression and cellular refractoriness gives rise to the eupnoea rhythm, whereas an intracellular calcium oscillation that is slower by orders of magnitude gives rise to the sigh rhythm. A mathematical model capturing these dynamics simultaneously generates eupnoea and sigh rhythms with disparate frequencies, which can be separately regulated by physiological parameters. We experimentally validated key model predictions regarding intracellular calcium signalling. All vertebrate brains feature a network oscillator that drives the breathing pump for regular respiration. However, in air-breathing mammals with compliant lungs susceptible to collapse, the breathing rhythmogenic network may have refashioned ubiquitous intracellular signalling systems to produce a second slower rhythm (for sighs) that prevents atelectasis without impeding eupnoea. KEY POINTS: A simplified activity-based model of the preBötC generates inspiratory and sigh rhythms from a single neuron population. Inspiration is attributable to a canonical excitatory network oscillator mechanism. Sigh emerges from intracellular calcium signalling. The model predicts that perturbations of calcium uptake and release across the endoplasmic reticulum counterintuitively accelerate and decelerate sigh rhythmicity, respectively, which was experimentally validated. Vertebrate evolution may have adapted existing intracellular signalling mechanisms to produce slow oscillations needed to optimize pulmonary function in mammals.

Лабораторные методы оценки функционирования цитокинов в ветеринарной практике

This review paper analyzes modern laboratory methods for assessing the functioning of cytokines in veterinary practice for the prevention, prevention and development of treatment plans for pathologies of various etiologies. Purpose of the work: to analyze laboratory methods for assessing the functioning of cytokines in veterinary practice. Materials and methods. For the study, we used the resources of the Elibrary and PubMed search engines on this topic. Research results. A brief description of cytokines and their biological activity is presented. Laboratory methods for assessing the functioning of the cytokine system include: genetic analysis of mutations in the genes of cytokine receptors and proteins of intracellular signaling systems that trigger synthesis and signal transmission; analysis of cytokine gene polymorphism; study of cytokine gene expression; studying the level of cytokine production by cells in culture; determination of cytokine concentrations in biological fluids; study of cytokine synthesis at the level of individual cells; study of cytokine synthesis in tissues.

Use of Janus kinase inhibitors in atopic dermatitis - an update.

Atopic dermatitis is among the cutaneous inflammatory disorders whose pathophysiology is thought to be influenced by the JAK-STAT intracellular signalling system. The effectiveness of systemic and topical Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis has been shown in clinical trials and case studies. At present, oral abrocitinib (Cibinqo), oral upadacitinib (Rinvoq), oral baricitinib (Olumiant) and topical ruxolitinib (Opzelura) have approval from the US-FDA for their use in the treatment of atopic dermatitis. The efficacy and safety of oral and topical Janus kinase inhibitors for the treatment of atopic dermatitis have been reviewed in this article.

THE ROLE OF CAMP IN THE TOPOGRAPHIC ORGANIZATION OF THE OLFACTORY SYSTEM

The article analyzes the literature data on the role of molecular olfactory receptors (OR) and cAMP in the formation of the topographic organization of the olfactory sensory system. Before its transmission to the brain, sensory information is already organized in the peripheral region according to the “one neuron–one receptor” principle, which also extends to the glomeruli in the olfactory bulb, which obey the “one glomerulus–one receptor” law. At present, an important role in the formation of the sensory map has been attributed to ORs, which plays a dual role in the organization of the olfactory system, since they are localized both in the olfactory cilia (OC) and in the membrane of the axon growth cone of the same olfactory sensory neuron (OSN), and determine the target for the axons of the OSN in the olfactory bulb (OB). However, there is strong evidence for the central role of the intracellular cAMP signaling system in sensory map development. Using the method of genetic mutation with the abolition of cAMP synthesis, it was revealed that the axons carrying this mutation never penetrate the glomerular layer, but remain in the layer of the olfactory nerve. At the same time, OSN axons target the OB but fail to form distinct and well-defined glomeruli, many of which become heterogeneous because they contain fibers belonging to OSNs expressing ORs for different odorants. Thus, cAMP synthesized in the tip of the RSN axon, under the action of signals from the OB, regulates the expression of molecules of its navigation to its target in the OB, and also forms intrabulbar chemical and electrical synapses, forming neuronal circuits. Numerous clinical and experimental data have led to the conclusion that the pathogenetic mechanisms of the development of some psychiatric diseases are associated with dysregulation of cAMP.

PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target.

In a previous study, protein tyrosine phosphatase non-receptor type (PTPN) 3 was identified as an immune checkpoint molecule in lymphocytes, and its potential as a novel target for cancer immunotherapy was anticipated. However, evaluation of dendritic cell (DC) function as antigen-presenting cells is critical for the development of immunotherapy. In this study, we aimed to analyze the biological effect of PTPN3 on DCs induced from human peripheral blood monocytes obtained from healthy individuals. We used short-interfering RNA to knock down PTP3 in DCs. For DC maturation, we added cancer cell lysate and tumor necrosis factor-α/interferon-α to immature DCs. In the cytotoxic assay, the target cancer cells were SBC5, unmatched with DCs from healthy human leukocyte antigen (HLA)-A24, or Sq-1, matched with DCs. Enzyme-linked immunosorbent assay was used to determine the amount of cytokines. To examine the intracellular signaling system, intracellular staining was used. PTPN3 knockdown significantly increased the number of DCs, expression of CD80 and chemokine receptor (CCR)7, and production of interleukin-12p40/p70 in mature DCs. In the HLA-A24-restricted DC and human lung squamous cell carcinoma cell cytotoxic assay, inhibition of PTPN3 expression in mature DCs induced cytotoxic T lymphocytes with increased production of INF-γ and granzyme B, and enhanced toxicity against cancer cells and migration to cancer. Furthermore, inhibition of PTPN3 expression activated the mitogen-activated protein kinase pathway in DCs. Based on our findings, inhibition of PTPN3 expression could contribute to the development of novel cancer immunotherapies that activate not only lymphocytes but also DCs.

Клініко-генетичні характеристики дітей раннього віку з епілептичними енцефалопатіями та їхня роль у розвитку розладів аутистичного спектра

Purpose - to analyze the clinical and genetic characteristics of young children with developmental and epileptic encephalopathies and to determine their role in the formation of autism spectrum disorders (ASD). Materials and methods. The study included 58 children aged 0-3 years with the onset of epileptic seizures in the first year of life, clinical manifestations of developmental and epileptic encephalopathies with genetic etiology. The examination included assessment of neurological status, collection of anamnesis, assessment of semiology and determination of seizure type, assessment of development and screening for ASD at the age of 18 and 24 months, night sleep electroencephalography (video EEG), brain magnetic resonance imaging (MRI), screening for pathogenic variants by whole-exome sequencing or examination of relevant gene panels. Pathogenic variants of 33 different genes were found in the examined children. Pathogenic variants of genes responsible for the function of ion channels (41.3%), intracellular signaling systems (17.2%), organelles and intracellular membranes (12.1%) were most frequently found. 44.8% of children had symptoms of ASD at the age of 18 months, and 68.9% of children at the age of 24 months. The predominant types of epileptic seizures were myoclonic (37.9%) and focal clonic (34.4%). According to video EEG monitoring, interictal focal (39.6%) and multifocal (22.4%) epileptiform changes dominated in the examined children. According to MRI, structural changes of the brain were found in 86.2% of children. Conclusions. It is shown that children with a history of myoclonic seizures (RR=1.264) and infantile spasms (RR=1.44) have a high risk of developing ASD at 24 months. It has been established that there is a positive relationship between the presence in the child of mutations in the genes responsible for the functioning of ion channels (RR=1.32), as well as for the functioning of synapses, neurotransmitters and receptors (RR=1.5) and the development of ASD in 24 months. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Bioethics and Deontology Commission. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors.

The structural basis of β2 integrin intra-cellular multi-protein complexes.

In multicellular organisms, cell adhesion is a pivotal physiological process which is essential for cell-cell communications, cell migration, and interactions with extracellular matrix. Integrins, a family of large hetero-dimeric type I membrane proteins, are known for driving cell adhesion functions. Among 24 different integrins, four β2 integrins, αL β2, αM β2, αX β2 and αD β2, are specific for cell adhesion and migration of leukocytes. Many cytosolic proteins interact with short cytosolic tails (CTs) of β2 and other integrins which are essential in bi-directional signaling processes. Further, phosphorylation of CTs of integrins regulates binding of intra-cellular proteins and signaling systems. In this review, recent advances in structures and interactions of multi-protein complexes of integrin tails, with a focus on β2 integrin, and cytosolic proteins are discussed along with a proposed future direction.

Перспективы применения ингибиторов янус-киназ в терапии анкилозирующего спондилита и псориатического артрита

The Janus kinase inhibitors are oral targeted synthetic basic anti-inflammatory drugs that exert their influence on the intracellular signaling system, preventing the activation of inflammatory processes. Now, there are a sufficient number of janus kinase inhibitors that have found application not only in rheumatology, but also in other specialties (gastroenterology, dermatology, hematology, oncology and even veterinary medicine). Thanks to janus kinase inhibitors, suppression of the intracellular signaling pathway of several cytokines simultaneously became available, as a result of which it became possible to exert a complex pathogenic effect. This explains the wide range of applications of these drugs in many areas of medicine. In rheumatology, janus kinase inhibitors are finding new and new applications in the treatment of not only rheumatoid arthritis, but also other diseases. This article presents studies on ankylosing spondylitis and psoriatic arthritis, the results of which demonstrate high rates regarding the use of janus kinase inhibitors for the treatment of these diseases.

Roles of Intracellular Second Messengers in Mediation of a7-nAChR-induced Modulations

Nicotinic acetylcholine receptors (nAChRs) are the members of the cys-loop ligandgated ion channel superfamily. They are cation-selective membrane proteins with a homopentameric or heteropentameric structure. The α7 subtype of nAChR (α7-nAChR) belongs to the classical homopentameric structure with the characteristics of relatively low affinity to agonists and high permeability to Ca2+. α7-nAChR plays an important role in modulating learning and memory, cognition, anti-inflammatory, growth and development, and other processes. There are many possible mechanisms underlying α7-nAChR-mediated modulations, including opening the high Ca2+ permeable channels, regulating presynaptic neurotransmitter release, and altering intracellular second messenger-mediated signaling pathways. Here, we summarize the signal pathways associated with α7-nAChR activation involving nucleotides, ions, lipids, and gas molecules. This article provides insights into α7-nAChR-mediated modulations through intracellular signaling systems and helps to understand the α7-nAChR-associated pathogenesis and therapeutics of a variety of diseases and disorders.

Selective reversible JAK1 inhibitor in the treatment of moderate and severe atopic dermatitis

In recent decades, industrialized countries have recorded a steady increase in the incidence of atopic dermatitis (AD). The pathogenesis of AD is complex and diverse and includes hereditary determinism leading to a disruption of the skin barrier, as well as the Th2 immune response, which is supported by a wide range of pro-inflammatory mediators released by immunocompetent and epithelial cells, which play a key role in the activation and maintenance of inflammation in the skin. Progress in the treatment of immunoinflammatory diseases, including in the skin, has been achieved with the advent of a new class of targeted synthetic oral immunomodulatory drugs, Janus kinase inhibitors. Janus kinases are part of the JAK – STAT intracellular signaling system; STAT proteins are responsible for signaling more than 60 cytokines, hormones and growth factors that regulate key cellular processes. Currently, second generation JAK inhibitors have been developed, such as upadacitinib (trade name Rinvoq), which distinguish them from non-selective JAK inhibitors by their selectivity for certain JAK isoforms. In June 2021, the Ministry of Health of the Russian Federation approved the use of upadacitinib (UPA) for the indication “treatment of moderate to severe atopic dermatitis in adults and children aged 12 years and older who are indicated for treatment with systemic drugs”; the drug can be used in monotherapy or in combination with topical therapy in adults at a dose of 15 or 30 mg per day depending on the individual characteristics of the course, in adolescents weighing at least 40 kg – at a dose of 15 mg per day. Results from a Phase 3 clinical trial program involving more than 2500 patients worldwide in three global key studies: Measure Up 1, Measure Up 2 (UPA monotherapy at a dose of 15 mg or 30 mg per day) and AD Up (UPA in the same doses in combination with topical glucocorticosteroids (TGCS) demonstrated high efficacy and favorable benefit/risk profile of UPA both in monotherapy and in combination with TGCS in patients with moderate to severe AD.

Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression.

Scientific evidence that circadian rhythms affect pharmacokinetics and pharmacodynamics has highlighted the importance of drug dosing-time. Circadian oscillations alter drug absorption, distribution, metabolism, and excretion (ADME) as well as intracellular signaling systems, target molecules (e.g., receptors, transporters, and enzymes), and gene transcription. Although several antidepressant drugs are clinically available, less than 50% of depressed patients respond to first-line pharmacological treatments. Chronotherapeutic approaches to enhance the effectiveness of antidepressants are not completely known. Even so, experimental results found until this day suggest a positive influence of drug dosing-time on the efficacy of depression therapy. On the other hand, antidepressants have also demonstrated to modulate circadian rhythmicity and sleep–wake cycles. This review aims to evidence the potential of chronotherapy to improve the efficacy and/or safety of antidepressants. It includes pre-clinical and clinical studies that demonstrate the relevance of determining the most appropriate time of administration for antidepressant drugs. In parallel, their positive influence on the resynchronization of disrupted circadian rhythms is also herein discussed. It is expected that this review will promote the investigation of chronotherapy for the treatment of depression, contribute to a better understanding of the relationship between antidepressants and circadian rhythms, and consequently promote the development of new therapeutics.

The Action of Oil-Related Environmental Pollutants on Male Reproductive System

The low-weight aromatic hydrocarbons benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX), are among the most common hazardous sources of environmental contamination. The present review is the first summarization the data obtained during epidemiological, animals and cell culture studies concerning BTEX action on different aspects of male reproductiontesticular cell apoptosis, spermatogenesis, cytogenetics, pituitary and peripheral hormones and intracellular signaling systems. Analysis of the available literature demonstrates that BTEX can exert hazardous effects on various reproductive sites, including the pituitary-gonadal axis, hormone receptors and intracellular signaling molecules, testicular cell apoptosis, spermatogenesis and fertility. There are indications, that BTEX reproductive effects could be due to the ability of BTEX to affect embryonal gonads, to induce testicular cell mutagenesis and destroy chromosomes, to promote accumulation of free radicals, to affect hormones and hormonal receptors, cell cycle and CNS structures regulating reproduction, but only the role of free radicals in mediating BTEX action on male reproduction has been proven by experiments yet. Some approaches to prevent negative action of BTEX are outlined.

Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems.

Nausea and vomiting are common gastrointestinal complaints that can be triggered by diverse emetic stimuli through central and/or peripheral nervous systems. Both nausea and vomiting are considered as defense mechanisms when threatening toxins/drugs/bacteria/viruses/fungi enter the body either via the enteral (e.g., the gastrointestinal tract) or parenteral routes, including the blood, skin, and respiratory systems. While vomiting is the act of forceful removal of gastrointestinal contents, nausea is believed to be a subjective sensation that is more difficult to study in nonhuman species. In this review, the authors discuss the anatomical structures, neurotransmitters/mediators, and corresponding receptors, as well as intracellular emetic signaling pathways involved in the processes of nausea and vomiting in diverse animal models as well as humans. While blockade of emetic receptors in the prevention of vomiting is fairly well understood, the potential of new classes of antiemetics altering postreceptor signal transduction mechanisms is currently evolving, which is also reviewed. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide potential answers.

To what extent do sexual hormones influence bipolar disorder?

IntroductionIt is known that female reproductive events and hormonal treatments can impact the course of bipolar disorder (BD) in women, some of whom are more vulnerable to the development of mood instability under periods of hormonal fluctuation. The mechanisms involved are, however, largely unknown. The aim of this work is to review the impact of sexual hormones on the course of BD, regarding a clinical case.ObjectivesTo explore the role of sexual hormones in BD.MethodsLiterature review using Medline database.ResultsThis is a case of a 36-year-old woman with type 1 BD who develops a manic episode after starting oral contraception (OC). This episode remitted with suspension of the pill. Estrogen and progesterone are involved in various aspects of brain function, such as brain development, synaptic plasticity, and modulation of neurotransmitter systems. Studies indicate that there is a relationship between ovarian hormones and intracellular signaling systems involved in the pathophysiology of BD. However, research on OC use in patients with mood disorders is limited. Recent studies state that OC aren’t associated with a worse clinical course and don’t negatively influence BD, while other studies show there is a subgroup of bipolar women that improve with hormonal stability, while others get worse.ConclusionsFurther studies are needed to determine possible relationships between sexual hormones and BD, and it is essential to identify patients vulnerable to these risks by measuring baseline hormone levels, assessing hormone sensitivity through a history of mood changes during menstrual cycle and a history of previous mental health problems.DisclosureNo significant relationships.

Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy.

Several mood-stabilizing atypical antipsychotics and antidepressants weakly block serotonin (5-HT) receptor type-7 (5-HT7R); however, the contributions of 5-HT7R antagonism to clinical efficacy and pathophysiology are yet to be clarified. A novel mood-stabilizing antipsychotic agent, lurasidone exhibits predominant binding affinity to 5-HT7R when compared with other monoamine receptors. To date, we have failed to discover the superior clinical efficacy of lurasidone on schizophrenia, mood, or anxiety disorders when compared with conventional mood-stabilizing atypical antipsychotics; however, numerous preclinical findings have indicated the possible potential of 5-HT7R antagonism against several neuropsychiatric disorders, as well as the generation of novel therapeutic options that could not be expected with conventional atypical antipsychotics. Traditional experimental techniques, electrophysiology, and microdialysis have demonstrated that the effects of 5-HT receptor type-1A (5-HT1AR) and 5-HT7R on neurotransmission are in contrast, but the effect of 5-HT1AR is more predominant than that of 5-HT7R, resulting in an insufficient understanding of the 5-HT7R function in the field of psychopharmacology. Accumulating knowledge regarding the pharmacodynamic profiles of 5-HT7R suggests that 5-HT7R is one of the key players in the establishment and remodeling of neural development and cytoarchitecture during the early developmental stage to the mature brain, and dysfunction or modulation of 5-HT7R is linked to the pathogenesis/pathophysiology of neuropsychiatric and neurodevelopmental disorders. In this review, to explore candidate novel applications for the treatment of several neuropsychiatric disorders, including mood disorders, schizophrenia, and other cognitive disturbance disorders, we discuss perspectives of psychopharmacology regarding the effects of 5-HT7R antagonism on transmission and intracellular signaling systems, based on preclinical findings.

Recapitulation of the Function and Role of ROS Generated in Response to Heat Stress in Plants

In natural ecosystems, plants are constantly exposed to changes in their surroundings as they grow, caused by a lifestyle that requires them to live where their seeds fall. Thus, plants strive to adapt and respond to changes in their exposed environment that change every moment. Heat stress that naturally occurs when plants grow in the summer or a tropical area adversely affects plants’ growth and poses a risk to plant development. When plants are subjected to heat stress, they recognize heat stress and respond using highly complex intracellular signaling systems such as reactive oxygen species (ROS). ROS was previously considered a byproduct that impairs plant growth. However, in recent studies, ROS gained attention for its function as a signaling molecule when plants respond to environmental stresses such as heat stress. In particular, ROS, produced in response to heat stress in various plant cell compartments such as mitochondria and chloroplasts, plays a crucial role as a signaling molecule that promotes plant growth and triggers subsequent downstream reactions. Therefore, this review aims to address the latest research trends and understandings, focusing on the function and role of ROS in responding and adapting plants to heat stress.

Visualization and Manipulation of Intracellular Signaling.

Cells respond to a wide range of extracellular stimuli, and process the input information through an intracellular signaling system comprised of biochemical and biophysical reactions, including enzymatic and protein-protein interactions. It is essential to understand the molecular mechanisms underlying intracellular signal transduction in order to clarify not only physiological cellular functions but also pathological processes such as tumorigenesis. Fluorescent proteins have revolutionized the field of life science, and brought the study of intracellular signaling to the single-cell and subcellular levels. Much effort has been devoted to developing genetically encoded fluorescent biosensors based on fluorescent proteins, which enable us to visualize the spatiotemporal dynamics of cell signaling. In addition, optogenetic techniques for controlling intracellular signal transduction systems have been developed and applied in recent years by regulating intracellular signaling in a light-dependent manner. Here, we outline the principles of biosensors for probing intracellular signaling and the optogenetic tools for manipulating them.