Hormonal Signaling Systems Research Articles

The central renin–angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in the regulation of cognition and behavior as well as in the neuropathology of neurological and mental disorders. The angiotensin II type 1 receptor (AT1R) mediates most functional and neuropathology-relevant actions associated with the central RAS. However, an overarching comprehension to guide translation and utilize the therapeutic potential of the central RAS in humans is currently lacking. We conducted a comprehensive characterization of the RAS using an innovative combination of transcriptomic gene expression mapping, image-based behavioral decoding, and pre-registered randomized controlled discovery-replication pharmacological resting-state functional magnetic resonance imaging (fMRI) trials (N = 132) with a selective AT1R antagonist. The AT1R exhibited a particular dense expression in a subcortical network encompassing the thalamus, striatum, and amygdalo-hippocampal formation. Behavioral decoding of the AT1R gene expression brain map showed an association with memory, stress, reward, and motivational processes. Transient pharmacological blockade of the AT1R further decreased neural activity in subcortical systems characterized by a high AT1R expression, while increasing functional connectivity in the cortico-basal ganglia-thalamo-cortical circuitry. Effects of AT1R blockade on the network level were specifically associated with the transcriptomic signatures of the dopaminergic, opioid, acetylcholine, and corticotropin-releasing hormone signaling systems. The robustness of the results was supported in an independent pharmacological fMRI trial. These findings present a biologically informed comprehensive characterization of the central AT1R pathways and their functional relevance on the neural and behavioral level in humans.

Comparative physiological and transcriptome analysis between potassium-deficiency tolerant and sensitive sweetpotato genotypes in response to potassium-deficiency stress

BackgroundSweetpotato is a typical ‘‘potassium (K+) favoring’’ food crop, which root differentiation process needs a large supply of potassium fertilizer and determine the final root yield. To further understand the regulatory network of the response to low potassium stress, here we analyze physiological and biochemical characteristics, and investigated root transcriptional changes in two sweetpotato genotypes, namely, - K tolerant “Xu32” and - K susceptible“NZ1”.ResultWe found Xu32 had the higher capability of K+ absorption than NZ1 with better growth performance, higher net photosynthetic rate and higher chlorophyll contents under low potassium stress, and identified 889 differentially expressed genes (DEGs) in Xu32, 634 DEGs in NZ1, 256 common DEGs in both Xu32 and NZ1. The Gene Ontology (GO) term in molecular function enrichment analysis revealed that the DEGs under low K+ stress are predominately involved in catalytic activity, binding, transporter activity and antioxidant activity. Moreover, the more numbers of identified DEGs in Xu32 than that in NZ1 responded to K+-deficiency belong to the process of photosynthesis, carbohydrate metabolism, ion transport, hormone signaling, stress-related and antioxidant system may result in different ability to K+-deficiency tolerance. The unique genes in Xu32 may make a great contribution to enhance low K+ tolerance, and provide useful information for the molecular regulation mechanism of K+-deficiency tolerance in sweetpotato.ConclusionsThe common and distinct expression pattern between the two sweetpotato genotypes illuminate a complex mechanism response to low potassium exist in sweetpotato. The study provides some candidate genes, which can be used in sweetpotato breeding program for improving low potassium stress tolerance.

Age-dependent dendrobine biosynthesis in Dendrobium nobile: insights into endophytic fungal interactions.

Dendrobium nobile (D. nobile), a valued Chinese herb known for its diverse pharmacological effects, owes much of its potency to the bioactive compound dendrobine. However, dendrobine content varies significantly with plant age, and the mechanisms governing this variation remain unclear. This study delves into the potential role of endophytic fungi in shaping host-microbe interactions and influencing plant metabolism. Using RNA-seq, we examined the transcriptomes of 1-year-old, 2-year-old, and 3-year-old D. nobile samples and through a comprehensive analysis of endophytic fungal communities and host gene expression in D. nobile stems of varying ages, we aim to identify associations between specific fungal taxa and host genes. The results revealing 192 differentially expressed host genes. These genes exhibited a gradual decrease in expression levels as the plants aged, mirroring dendrobine content changes. They were enriched in 32 biological pathways, including phagosome, fatty acid degradation, alpha-linolenic acid metabolism, and plant hormone signal transduction. Furthermore, a significant shift in the composition of the fungal community within D. nobile stems was observed along the age gradient. Olipidium, Hannaella, and Plectospherella dominated in 1-year-old plants, while Strelitziana and Trichomerium prevailed in 2-year-old plants. Conversely, 3-year-old plants exhibited additional enrichment of endophytic fungi, including the genus Rhizopus. Two gene expression modules (mediumpurple3 and darkorange) correlated significantly with dominant endophytic fungi abundance and dendrobine accumulation. Key genes involved in dendrobine synthesis were found associated with plant hormone synthesis. This study suggests that the interplay between different endophytic fungi and the hormone signaling system in D. nobile likely regulates dendrobine biosynthesis, with specific endophytes potentially triggering hormone signaling cascades that ultimately influence dendrobine synthesis.

Structural and functional characterization of an egg-laying hormone signaling system in a lophotrochozoan – The pacific oyster (Crassostrea gigas)

The egg-laying hormones (ELHs) of gastropod mollusks were characterized more than forty years ago. Yet, they have remained little explored in other mollusks. To gain insights into the functionality of the ELH signaling system in a bivalve mollusk – the oyster Crassostrea gigas, this study investigates the processing of its ELH precursor (Cragi-ELH) by mass spectrometry. Some of the ELH mature peptides identified in this study were subsequently investigated by nuclear magnetic resonance and shown to adopt an extended alpha-helix structure in a micellar medium mimicking the plasma membrane. To further characterize the ELH signaling system in C. gigas, a G protein-coupled receptor phylogenetically related to ecdysozoan diuretic hormone DH44 and corticotropin-releasing hormone (CRH) receptors named Cragi-ELHR was also characterized functionally and shown to be specifically activated by the two predicted mature ELH peptides and their N-terminal fragments. Both Cragi-ELH and Cragi-ELHR encoding genes were mostly expressed in the visceral ganglia (VG). Cragi-ELH expression was significantly increased in the VG of both fully mature male and female oysters at the spawning stage. When the oysters were submitted to a nutritional or hyposaline stress, no change in the expression of the ligand or receptor genes was recorded, except for Cragi-ELHR only during a mild acclimation episode to brackish water. These results suggest a role of Cragi-ELH signaling in the regulation of reproduction but not in mediating the stress response in our experimental conditions.

Immunomodulatory and regenerative potentials of breast milk, prematurity and children’s heart

Recent expansion of fundamental knowledge on the physiology of lactation, and breast milk exosomes, stem cell biology, mother-child interactions from prenatal period to postnatal development requires a progressive, dynamic view from the scientific community and practicing physicians when analyzing known, generally accepted clinical phenomena and patterns (development of the immune system of infants and young children, natural and artificial feeding, features of postnatal development and growth of organs and tissues in children born prematurely). The components of the mother-breast-milk-infant triad are closely related to each other and influence developmental trajectory of the infant. According to modern concepts, breast milk of a nursing woman is a “living, metabolic / endocrine signaling system”, which may be considered an “immune organ” significant for postnatal growth and body programming of a premature baby. A valuable phenomenon of early postnatal development is actively discussed in the special literature, i,e., “microchimerism” caused by breastfeeding which, according to modern concepts, may play a key role in development of immune system and the whole body. Absence of protective (immunomodulatory and regenerative) effects of breast milk from a nursing woman on the spontaneous, uncorrectable impact of adverse factors of prematurity is likely predispose for remodeling and dysfunction of heart in prematurely born children, and, at longer range, in adults. The young children born prematurely show a unique cardiac phenotype characterized by reduced biventricular volume, relatively lower systolic and diastolic function, disproportionate muscle mass gain, clinically manifesting by increased risk of cardiovascular disease, hypertension, and decreased exercise tolerance. Hence, the premature birth may be considered a chronic disease state. Therefore, the natural feeding which provides a natural evolutionarily protective mechanism for the child’s heart should be attributed to the fundamental factors that play a vital role in prevention of cardiovascular diseases in prematurely born children and at later life periods.

Functional Characterization of Gonadotropin-Releasing Hormone and Corazonin Signaling Systems in Pacific Abalone: Toward Reclassification of Invertebrate Neuropeptides

Introduction: The proposed evolutionary origins and corresponding nomenclature of bilaterian gonadotropin-releasing hormone (GnRH)-related neuropeptides have changed tremendously with the aid of receptor deorphanization. However, the reclassification of the GnRH and corazonin (CRZ) signaling systems in Lophotrochozoa remains unclear. Methods: We characterized GnRH and CRZ receptors in the mollusk Pacific abalone, Haliotis discus hannai (Hdh), by phylogenetic and gene expression analyses, bioluminescence-based reporter, Western blotting, substitution of peptide amino acids, in vivo neuropeptide injection, and RNA interference assays. Results: Two Hdh CRZ-like receptors (Hdh-CRZR-A and Hdh-CRZR-B) and three Hdh GnRH-like receptors (Hdh-GnRHR1-A, Hdh-GnRHR1-B, and Hdh-GnRHR2) were identified. In phylogenetic analysis, Hdh-CRZR-A and -B grouped within the CRZ-type receptors, whereas Hdh-GnRHR1-A/-B and Hdh-GnRHR2 clustered within the GnRH/adipokinetic hormone (AKH)/CRZ-related peptide-type receptors. Hdh-CRZR-A/-B and Hdh-GnRHR1-A were activated by Hdh-CRZ (pQNYHFSNGWHA-NH₂) and Hdh-GnRH (pQISFSPNWGT-NH₂), respectively. Hdh-CRZR-A/-B dually coupled with the Gα_q and Gα_s signaling pathways, whereas Hdh-GnRHR1-A was linked only with Gα_q signaling. Analysis of substituted peptides, [I²S³]Hdh-CRZ and [N²Y³H⁴]Hdh-GnRH, and in silico docking models revealed that the N-terminal amino acids of the peptides are critical for the selectivity of Hdh-CRZR and Hdh-GnRHR. Two precursor transcripts for Hdh-CRZ and Hdh-GnRH peptides and their receptors were mainly expressed in the neural ganglia, and their levels increased in starved abalones. Injection of Hdh-CRZ peptide into abalones decreased food consumption, whereas Hdh-CRZR knockdown increased food consumption. Moreover, Hdh-CRZ induced germinal vesicle breakdown in mature oocytes. Conclusion: Characterization of Hdh-CRZRs and Hdh-GnRHRs and their cognate peptides provides new insight into the evolutionary route of GnRH-related signaling systems in bilaterians.

Growth hormone in fertility and infertility: Mechanisms of action and clinical applications

Secreted by the anterior pituitary gland, growth hormone (GH) is a peptide that plays a critical role in regulating cell growth, development, and metabolism in multiple targeted tissues. Studies have shown that GH and its functional receptor are also expressed in the female reproductive system, including the ovaries and uterus. The experimental data suggest putative roles for GH and insulin-like growth factor 1 (IGF-1, induced by GH activity) signaling in the direct control of multiple reproductive functions, including activation of primordial follicles, folliculogenesis, ovarian steroidogenesis, oocyte maturation, and embryo implantation. In addition, GH enhances granulosa cell responsiveness to gonadotropin by upregulating the expression of gonadotropin receptors (follicle-stimulating hormone receptor and luteinizing hormone receptor), indicating crosstalk between this ovarian regulator and the endocrine signaling system. Notably, natural gene mutation of GH and the age-related decline in GH levels may have a detrimental effect on female reproductive function, leading to several reproductive pathologies, such as diminished ovarian reserve, poor ovarian response during assisted reproductive technology (ART), and implantation failure. Association studies using clinical samples showed that mature GH peptide is present in human follicular fluid, and the concentration of GH in this fluid is positively correlated with oocyte quality and the subsequent embryo morphology and cleavage rate. Furthermore, the results obtained from animal experiments and human samples indicate that supplementation with GH in the in vitro culture system increases steroid hormone production, prevents cell apoptosis, and enhances oocyte maturation and embryo quality. The uterine endometrium is another GH target site, as GH promotes endometrial receptivity and pregnancy by facilitating the implantation process, and the targeted depletion of GH receptors in mice results in fewer uterine implantation sites. Although still controversial, the administration of GH during ovarian stimulation alleviates age-related decreases in ART efficiency, including the number of oocytes retrieved, fertilization rate, embryo quality, implantation rate, pregnancy rate, and live birth rate, especially in patients with poor ovarian response and recurrent implantation failure.

Potassium ion regulates hormone, Ca2+ and H2O2 signal transduction and antioxidant activities to improve salt stress resistance in tobacco

Although improvement of plant salt tolerance by potassium ions (K+) has been widely studied, whether the tolerance is mediated via hormone signaling or antioxidant systems remains to be explored. This study combined plant physiology with transcriptomic techniques to study how K+ interacts with hormones and antioxidant enzymes to improve plant salt tolerance. Tobacco was used as the test material to study the effects of exogenous potassium application on photosynthetic function, hormone signal transduction, and reactive oxygen species (ROS) production under NaCl stress. The study also evaluated the function of the Ca2+ signaling pathway in salt stress tolerance. Transcriptome data showed that 4413 up-regulated genes and 3743 down-regulated genes were found in tobacco leaves treated with NaCl compared with the control. Compared with NaCl, the down-regulated genes in tobacco leaves were significantly reduced under NaCl + KCL treatment. The results showed that NaCl stress caused oxidative damage to tobacco leaves due to increased superoxide anion (O2−) content, superoxide dismutase (SOD) dismutates superoxide anion to produce hydrogen peroxide and the accumulation of H2O2 caused by reduced ascorbate peroxidase (APX) and peroxidase (POD) activities. NaCl stress also increased abscisic acid (ABA) content in tobacco leaves, resulting in stomatal closure and reduced photosynthetic capacity. Transcriptome data showed that 5 SOD, 1 POD, 1 CAT, 5 APX, and 3 GPX genes were significantly down-regulated by the NaCl treatment. Contrarily, NaCl + KCl treatment reduced the accumulation of O2−and SOD activity but increased POD activity, thereby reducing the accumulation of H2O2 and alleviating oxidative damage. The expression of 2 SOD and 3 APX and 2 GPX genes was significantly higher in NaCl + KCl treatment than that in NaCl treatment. Sufficient K+ also increased indole acetic acid (IAA) levels in tobacco leaves under NaCl stress but reduced ABA content, promoting stomatal opening and improving the photosynthetic capacity. In conclusion, K+ can improve plant salt tolerance by alleviating oxidative damage and regulating hormone signal transduction.

The phytotoxicity of exposure to two polybrominated diphenyl ethers (BDE47 and BDE209) on photosynthesis and the response of the hormone signaling and ROS scavenging system in tobacco leaves

To reveal the response and adaptative mechanism of plants to the organic pollutants PBDEs, physiological and transcriptomic techniques were used to study the effects of exposure to BDE47 and BDE209 on tobacco (Nicotiana tabacum L.) plant growth, physiological function and response of key genes. Exposure to both BDE47 and BDE209 inhibited the growth of tobacco plants. The number of down-regulated DEGs following exposure to BDE47 was significantly higher than that following exposure to BDE209. Enrichment analysis using the KEGG showed that BDE47 and BDE209 primarily affected tobacco leaf photosynthesis-antenna proteins, photosynthesis, plant hormone signal transduction and α-linolenic acid metabolism. BDE47 primarily inhibits the synthesis of Chl a, and BDE209 has a more significant impact on Chl b. Most photosynthesis-related DEGs were concentrated in PSII and PSI; the number of down-regulated DEGs in PSI was significantly higher than that in PSII, and the range in which the PSI activity was reduced was also higher than that of PSII, i.e., PSII and PSI (particularly PSI) were sensitive to the effects of exposure to BDE47 and BDE209 on photosynthesis. The increase of the ratio of regulatory energy dissipation played an important protective role in alleviating the photoinhibition of PSII. Exposure to BDE47 and BDE209 can lead to the accumulation of ROS in tobacco leaves, but correspondingly, the activities of antioxidant enzymes SOD, POD, CAT, APX and GPX and the up-regulated expression of their coding genes play an important role in preventing excessive oxidative damage. Exposure to BDE47 and BDE209 promoted the up-regulation of gene expression related to Pro synthesis. In particular, the Pro synthetic process of the Orn pathway was promoted. Exposure to BDE47 and BDE209 induced the up-regulated expression of genes related to the synthesis of ABA and JA, promoted the synthesis of ABA and JA, and activated ABA and JA signal transduction pathways. In conclusion, both BDE47 and BDE209 inhibit the synthesis of chlorophyll and hinder the process of light energy capture and electron transfer in tobacco leaves. BDE47 was more toxic than BDE209. However, tobacco leaves can also adapt to BDE47 and BDE209 by regulating the antioxidant system, accumulating Pro and initiating the hormone signal transduction process. The results of this study provide a theoretical basis for the phytotoxicity mechanism of PBDEs.

Evolutionary Adaptation of the Thyroid Hormone Signaling Toolkit in Chordates.

The specification of the endostyle in non-vertebrate chordates and of the thyroid gland in vertebrates are fundamental steps in the evolution of the thyroid hormone (TH) signaling to coordinate development and body physiology in response to a range of environmental signals. The physiology and biology of TH signaling in vertebrates have been studied in the past, but a complete understanding of such a complex system is still lacking. Non-model species from non-vertebrate chordates may greatly improve our understanding of the evolution of this complex endocrine pathway. Adaptation of already existing proteins in order to perform new roles is a common feature observed during the course of evolution. Through sequence similarity approaches, we investigated the presence of bona fide thyroid peroxidase (TPO), iodothyronine deiodinase (DIO), and thyroid hormone receptors (THRs) in non-vertebrate and vertebrate chordates. Additionally, we determined both the conservation and divergence degrees of functional domains at the protein level. This study supports the hypothesis that non-vertebrate chordates have a functional thyroid hormone signaling system and provides additional information about its possible evolutionary adaptation.

DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling.

Many cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematode Caenorhabditis elegans when adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular, and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor (TF) effectors of 3 different hormonal signaling systems, the insulin-responsive DAF-16/FoxO TF, the TGFβ-responsive DAF-3/SMAD TF, and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor (VDR), were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all 3 TFs are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell-autonomously to control anatomical, molecular, and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent interorgan signaling axes. Our findings provide novel perspectives into how hormonal systems control tissue remodeling.

Maternal GABAergic and GnRH/corazonin pathway modulates egg diapause phenotype of the silkworm Bombyx mori

Diapause represents a major developmental switch in insects and is a seasonal adaptation that evolved as a specific subtype of dormancy in most insect species to ensure survival under unfavorable environmental conditions and synchronize populations. However, the hierarchical relationship of the molecular mechanisms involved in the perception of environmental signals to integration in morphological, physiological, behavioral, and reproductive responses remains unclear. In the bivoltine strain of the silkworm Bombyx mori, embryonic diapause is induced transgenerationally as a maternal effect. Progeny diapause is determined by the environmental temperature during embryonic development of the mother. Here, we show that the hierarchical pathway consists of a γ-aminobutyric acid (GABA)ergic and corazonin signaling system modulating progeny diapause induction via diapause hormone release, which may be finely tuned by the temperature-dependent expression of plasma membrane GABA transporter. Furthermore, this signaling pathway possesses similar features to the gonadotropin-releasing hormone (GnRH) signaling system for seasonal reproductive plasticity in vertebrates.

Expression Profiling, Downstream Signaling, and Inter-subunit Interactions of GPA2/GPB5 in the Adult Mosquito Aedes aegypti.

GPA2/GPB5 and its receptor constitute a glycoprotein hormone-signaling system native to the genomes of most vertebrate and invertebrate organisms. Unlike the well-studied gonadotropins and thyrotropin, the exact function of GPA2/GPB5 remains elusive, and whether it elicits its functions as heterodimers, homodimers or as independent monomers remains unclear. Here, the glycoprotein hormone signaling system was investigated in adult mosquitoes, where GPA2 and GPB5 subunit expression was mapped and modes of its signaling were characterized. In adult Aedes aegypti mosquitoes, GPA2 and GPB5 transcripts co-localized to bilateral pairs of neuroendocrine cells, positioned within the first five abdominal ganglia of the central nervous system. Unlike GPA2/GPB5 homologs in human and fly, GPA2/GPB5 subunits in A. aegypti lacked evidence of heterodimerization. Rather, cross-linking analysis to determine subunit interactions revealed A. aegypti GPA2 and GPB5 subunits may form homodimers, although treatments with independent subunits did not demonstrate receptor activity. Since mosquito GPA2/GPB5 heterodimers were not evident by heterologous expression, a tethered fusion construct was generated for expression of the subunits as a single polypeptide chain to mimic heterodimer formation. Our findings revealed A. aegypti LGR1 elicited constitutive activity with elevated levels of cAMP. However, upon treatment with recombinant tethered GPA2/GPB5, an inhibitory G protein (Gi/o) signaling cascade is initiated and forskolin-induced cAMP production is inhibited. These results further support the notion that heterodimerization is a requirement for glycoprotein hormone receptor activation and provide novel insight to how signaling is achieved for GPA2/GPB5, an evolutionary ancient neurohormone.

CAPA neuropeptides and their receptor form an anti-diuretic hormone signaling system in the human disease vector, Aedes aegypti

Insect CAPA neuropeptides are homologs of mammalian neuromedin U and are known to influence ion and water balance by regulating the activity of the Malpighian ‘renal’ tubules (MTs). Several diuretic hormones are known to increase primary fluid and ion secretion by insect MTs and, in adult female mosquitoes, a calcitonin-related peptide (DH31) called mosquito natriuretic peptide, increases sodium secretion to compensate for the excess salt load acquired during blood-feeding. An endogenous mosquito anti-diuretic hormone was recently described, having potent inhibitory activity against select diuretic hormones, including DH31. Herein, we functionally deorphanized, both in vitro and in vivo, a mosquito anti-diuretic hormone receptor (AedaeADHr) with expression analysis indicating highest enrichment in the MTs where it is localized within principal cells. Characterization using a heterologous in vitro system demonstrated the receptor was highly sensitive to mosquito CAPA neuropeptides while in vivo, AedaeADHr knockdown abolished CAPA-induced anti-diuretic control of DH31-stimulated MTs. CAPA neuropeptides are produced within a pair of neurosecretory cells in each of the abdominal ganglia, whose axonal projections innervate the abdominal neurohaemal organs, where these neurohormones are released into circulation. Lastly, pharmacological inhibition of nitric oxide synthase (NOS) and protein kinase G (PKG) signaling eliminated anti-diuretic activity of CAPA, highlighting the role of the second messenger cGMP and NOS/PKG in this anti-diuretic signaling pathway.

Induced resistance to the greenbug aphid Schizaphis graminum Rond. in species of the genus Triticum

The greenbug aphid Schizaphis graminum Rond. causes a significant loss of the grain harvest. Therefore, to improve plant resistance to aphids is one of the topical tasks. The problem of creating varieties resistant to phloem-feeding insects is quite urgent, since the mechanisms procuring the resistance of plants to insects are not fully understood. Nevertheless, modern literature describes some mechanisms associated with changes in the redox state of colonized plants. Besides, attention is being increasingly focused on the study of mechanisms that underlie inducible resistance to aphids in wheat and are regulated by hormonal signaling systems. To detect connections among the redox status, indicators of resistance (antibiosis and endurance) of wheat plants to the pest, and induction of the jasmonate (JA) and salicylate (SA) signaling pathways, we studied accessions of three species of wheat plants – Triticum aestivum L., T. monococcum., and T. timopheevii Zhuk.– infested with S. graminum greenbugs by physiological, biochemical, and molecular methods. Analysis of antibiosis and endurance showed that T. timopheevii k-58666 and T. monococcum k-39471 were resistant to S. graminum, the latter accession being the most enduring. High hydrogen peroxide contents and high peroxidase activities were detected in the resistant plants. We investigated the expression of genes encoding PR proteins, including markers and regulators of the salicylate (TaRboh, TaPAL, Tapr1, TaPrx) and jasmonate (TaPI, TaLOX, TaPrx) signaling pathways. At the early stage of infestation in the susceptible T. aestivum variety Salavat Yulaev, the expression of only jasmonate-dependent genes was activated in response to plant damage. In the resistant T. timopheevii accession k-58666, expression of only salicylate-dependent genes was activated, while the aphid reproduction was practically absent. In the resistant T. monococcum accession k-39471, expression was activated in both the salicylate-dependent and jasmonate-dependent gene groups. We assume that the oxidative burst in the resistant forms of wheat was induced via the activation of the SA signaling pathway, which was of crucial importance in the further cascade of chemical reactions leading to the development of resistance.

Local Hemostatic Measures in Oral and Maxillofacial Surgery

Homeostasis is continuous process by which internal body system monitor and maintain constant internal environment. Blood is a connective tissue in fluid state closely connected to all tissues of the body. It has many roles including transport of nutrients, metabolic products, blood gases, thermal regulation hormone signaling system, heat conduction, immune response. Hemostasis is homeostasis of intravascular blood volume and is an important function of blood. It involves four major steps: vasoconstriction, platelet aggregation, coagulation and fibrinolysis [1]. The phase of vasoconstriction reduces the blood flow in preparation for platelet aggregation phase. However, the larger the size of the injured blood vessel the less possibility of vasoconstriction especially with high pressure.

An Introduction to Evolutionary Physiology, with an Example of Experimental Evolution

By 1950, comparative physiology was an established subfield whose broad agenda included (1) cataloging diversity, (2) using physiological information to reconstruct phylogenetic relationships, (3) elucidating how physiology mediates interactions between organisms and their environments, (4) identifying model systems for studying particular functions, and (5) using kind of organism as a pseudo‐experimental variable. Physiological ecology developed somewhat later, with an emphasis on the third goal. Both fields always had an evolutionary component, but only in the late 1970s did evolutionary physiology arise, borrowing rigorous inferential approaches from evolutionary biology and population/quantitative genetics. This newer subfield uses a range of approaches to ask whether the way organisms work influences the ways they evolve, and if so, how. Approaches include phylogenetically informed comparative studies, measurement of selection in wild populations, quantitative genetic analysis of trait heritabilities and correlations, and identification of genes involved in the adaptive process.Two primary foci of evolutionary physiology are the evolution of complex traits and the key role that organismal performance plays in mediating how natural and sexual selection act on individual variation within populations. Selection is often viewed as acting most directly on behavior (what an animal does in a given situation), which cannot exceed an animal's performance abilities (e.g., how fast it can sprint), which in turn depend on lower‐level morphological, physiological, and biochemical traits (e.g., muscle fiber type composition). If so, then behavior will often be at the leading edge of evolutionary (genetic) responses to selection. Moreover, given that animals usually have some excess capacity to perform relative to their typical daily activities, behavior may evolve to some extent without accompanying changes in exercise capacities. We have addressed this “behavior evolves first” hypothesis with experimental evolution.For >85 generations, we have bred 4 replicate lines of lab house mice for high voluntary wheel‐running behavior on days 5 and 6 of a 6‐day period of wheel access as young adults. The lines evolved rapidly, reaching selection limits after 17–27 generations, depending on line and sex. At these limits, mice from the High Runner lines ran ~3‐fold more than those from 4 non‐selected Control lines, due more to increased average running speed than the duration of daily running, but these two components show a trade‐off among the 4 HR lines. Studies aimed at uncovering the motivational/neurobiological basis of increased running have identified changes in specific brain regions (e.g., striatum), in multiple neural and endocrine signaling systems (e.g., dopamine, serotonin, endocannabinoids), and some evidence for exercise addiction. The evolution of high voluntary exercise has engendered various correlated responses, including reduced body size and body fat, increased maximal aerobic capacity and running endurance during forced treadmill exercise, larger joint surfaces, changes in inner ear morphology, reduced hindlimb muscle mass, alterations in circulating hormone concentrations, and increased adaptive plasticity in several traits.Support or Funding InformationU.S. N.S.F. DEB‐1655362This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Glycoprotein Hormone Receptor Knockdown Leads to Reduced Reproductive Success in Male Aedes aegypti.

Glycoprotein hormone receptors mediate a diverse range of physiological functions in vertebrate and invertebrate organisms. The heterodimeric glycoprotein hormone GPA2/GPB5 and its receptor LGR1, constitute a recently discovered invertebrate neuroendocrine signaling system that remains to be functionally characterized. We previously reported that LGR1 is expressed in the testes of adult Aedes aegypti mosquitoes, where its immunoreactivity is particularly regionalized. Here, we show that LGR1 immunoreactivity is associated with the centriole adjunct of spermatids and is observed transiently during spermatogenesis in mosquitoes, where it may act to mediate the regulation of flagellar development. RNA interference to downregulate LGR1 expression was accomplished by feeding mosquito larvae with bacteria that produced LGR1-specific dsRNA, which led to defects in spermatozoa, characterized with shortened flagella. LGR1 knockdown mosquitoes also retained ∼60% less spermatozoa in reproductive organs and demonstrated reduced fertility compared to controls. To date, the endocrine regulation of spermatogenesis in mosquitoes remains an understudied research area. The distribution of LGR1 and detrimental effects of its knockdown on spermatogenesis in A. aegypti indicates that this heterodimeric glycoprotein hormone signaling system contributes significantly to the regulation of male reproductive biology in this important disease-vector.

Expression and activity of lipid and oxidative metabolism enzymes following elevated temperature exposure and thyroid hormone manipulation in juvenile lake whitefish (Coregonus clupeaformis)

Temperature has unequivocal effects on several aspects of fish physiology, but the full extent of its interaction with key endocrine signaling systems to influence metabolic function remains unknown. The aim of the current study was to assess the individual and combined effects of elevated temperature and hyperthyroidism on hepatic metabolism in juvenile lake whitefish by quantifying mRNA abundance and activity of key metabolic enzymes. Fish were exposed to 13 (control), 17 or 21 °C for 0, 4, 8 or 24 days in the presence or absence of low-T4 (1 µg × g body weight−1) or high-T4 (10 µg × g body weight−1) treatment. Our results demonstrate moderate sensitivity to elevated temperature in this species, characterized by short-term changes in mRNA abundance of several metabolic enzymes and long-term declines in citrate synthase (CS) and cytochrome c oxidase (COX) activities. T4-induced hyperthyroidism also had several short-term effects on mRNA abundance of metabolic transcripts, including depressions in acetyl-coA carboxylase β (accβ) and carnitine palmitoyltransferase 1β (cpt1β), and stabilization of cs mRNA levels; however, these effects were primarily limited to elevated temperature groups, indicating temperature-dependent effects of exogenous T4 treatment in this species. In contrast, maximal CS and COX activities were not altered by hyperthyroidism at any temperature. Collectively, our data suggest that temperature has the potential to manipulate thyroid hormone physiology in juvenile lake whitefish and, under warm-conditions, hyperthyroidism may suppress certain elements of the β-oxidation pathway without substantial impacts on overall cellular oxidative capacity.

Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications.

BACKGROUNDNeurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)] and glial cell line-derived neurotrophic factor (GDNF) are soluble polypeptide growth factors that are widely recognized for their roles in promoting cell growth, survival and differentiation in several classes of neurons. Outside the nervous system, neurotrophin (NT) and GDNF signaling events have substantial roles in various non-neural tissues, including the ovary.OBJECTIVE AND RATIONALEThe molecular mechanisms that promote and regulate follicular development and oocyte maturation have been extensively investigated. However, most information has been obtained from animal models. Even though the fundamental process is highly similar across species, the paracrine regulation of ovarian function in humans remains poorly characterized. Therefore, this review aims to summarize the expression and functional roles of NTs and GDNF in human ovarian biology and disorders, and to describe and propose the development of novel strategies for diagnosing, treating and preventing related abnormalities.SEARCH METHODSRelevant literature in the English language from 1990 to 2018 describing the role of NTs and GDNF in mammalian ovarian biology and phenotypes was comprehensively selected using PubMed, MEDLINE and Google Scholar.OUTCOMESStudies have shown that the neurotrophins NGF, BDNF, NT-3 and NT-4 as well as GDNF and their functional receptors are expressed in the human ovary. Recently, gathered experimental data suggest putative roles for NT and GDNF signaling in the direct control of ovarian function, including follicle assembly, activation of the primordial follicles, follicular growth and development, oocyte maturation, steroidogenesis, ovulation and corpus luteum formation. Additionally, crosstalk occurs between these ovarian regulators and the endocrine signaling system. Dysregulation of the NT system may negatively affect ovarian function, leading to reproductive pathology (decreased ovarian reserve, polycystic ovary syndrome and endometriosis), female infertility and even epithelial ovarian cancers.WIDER IMPLICATIONSA comprehensive understanding of the expression, actions and underlying molecular mechanisms of the NT/GDNF system in the human ovary is essential for novel approaches to therapeutic and diagnostic interventions in ovarian diseases and to develop more safe, effective methods of inducing ovulation in ART in the treatment of female infertility.