Harmonic resonance and entrainment of propagating chemical waves by external mechanical stimulation in BZ self-oscillating hydrogels.

Smart polymer materials that are nonliving yet exhibit complex "life-like" or biomimetic behaviors have been the focus of intensive research over the past decades, in the quest to broaden our understanding of how living systems function under nonequilibrium conditions. Identification of how chemical and mechanical coupling can generate resonance and entrainment with other cells or external environment is an important research question. We prepared Belousov-Zhabotinsky (BZ) self-oscillating hydrogels which convert chemical energy to mechanical oscillation.

Estrogen and testosterone secretion from the mouse brain.

Estrogen and testosterone are typically thought of as gonadal or adrenal derived steroids that cross the blood brain barrier to signal via both rapid nongenomic and slower genomic signalling pathways. Estrogen and testosterone signalling has been shown to drive interlinked behaviours such as social behaviours and cognition by binding to their cognate receptors in hypothalamic and forebrain nuclei. So far, acute brain slices have been used to study short-term actions of 17β-estradiol, typically using electrophysiological measures.

Steroid hormone-mediated regulation of sexual and aggressive behaviour by non-genomic signalling.

Sex and aggression are well studied examples of social behaviours that are common to most animals and are mediated by an evolutionary conserved group of interconnected nuclei in the brain called the social behaviour network. Though glucocorticoids and in particular estrogen regulate these social behaviours, their effects in the brain are generally thought to be mediated by genomic signalling, a slow transcriptional regulation mediated by nuclear hormone receptors. In the last decade or so, there has been renewed interest in understanding the physiological significance of rapid, non-genomic signalling mediated by steroids.

Localisation of oestrogen receptors in stem cells and in stem cell-derived neurons of the mouse.

Oestrogen receptors (ER) transduce the effects of the endogenous ligand, 17β-estradiol in cells to regulate a number of important processes such as reproduction, neuroprotection, learning and memory and anxiety. The ERα or ERβ are classical intracellular nuclear hormone receptors while some of their variants or novel proteins such as the G-protein coupled receptor (GPCR), GPER1/GPR30 are reported to localise in intracellular as well as plasma membrane locations. Although the brain is an important target for oestrogen with oestrogen receptors expressed differentially in various nuclei, subcellular organisation and crosstalk between these receptors is under-explored.

mTOR-Dependent Spine Dynamics in Autism.

Autism Spectrum Conditions (ASC) are a group of neurodevelopmental disorders characterized by deficits in social communication and interaction as well as repetitive behaviors and restricted range of interests. ASC are complex genetic disorders with moderate to high heritability, and associated with atypical patterns of neural connectivity. Many of the genes implicated in ASC are involved in dendritic spine pruning and spine development, both of which can be mediated by the mammalian target of rapamycin (mTOR) signaling pathway.

Effect of Light-Emitting Diode Phototherapy on Serum Calcium Levels in Neonates With Jaundice.

Background: To assess the change in serum total calcium levels during light-emitting diode phototherapy treatment for jaundice in term neonates.

Methods: A prospective observational study was done on 104 term neonates with hyperbilirubinemia in a tertiary care center to investigate the effects of phototherapy using a light-emitting diode device. The total serum bilirubin along with total calcium levels was measured at the start and at the end of phototherapy.

Microplastics and Their Impact on Reproduction-Can we Learn From the Model?

Biologically active environmental pollutants have significant impact on ecosystems, wildlife, and human health. Microplastic (MP) and nanoplastic (NP) particles are pollutants that are present in the terrestrial and aquatic ecosystems at virtually every level of the food chain. Moreover, recently, airborne microplastic particles have been shown to reach and potentially damage respiratory systems.

Immunoblot Detection of the Phosphorylation of the Estrogen Receptor α as an Outcome of GPR30 /GPER1 Activation.

Phosphorylation of the serine residues in estrogen receptor (ER) α is important in transcriptional activation. Hence, methods to detect such posttranslational modification events are valuable. We describe, in detail, the analysis of the phosphorylated ERα by electrophoretic separation of proteins and subsequent immunoblotting techniques.

Delayed Mechanical Response to Chemical Kinetics in Self-Oscillating Hydrogels Driven by the Belousov-Zhabotinsky Reaction.

We show experimentally that chemical and mechanical self-oscillations in Belousov-Zhabotinsky hydrogels are inherently asynchronous, that is, there is a detectable delay in swelling-deswelling response after a change in the chemical redox state. This phenomenon is observable in many previous experimental studies and potentially has far-reaching implications for the functionality and response time of the material in future applications; however, so far, it has not been quantified or reported systematically. Here, we provide a comprehensive qualitative and quantitative description of the chemical-to-mechanical delay, and we propose to explain it as a consequence of the slow nonequilibrium swelling-deswelling dynamics of the polymer material.

Does GPER1 Play a Role in Sexual Dimorphism?

Estrogens are critical in driving sex-typical social behaviours that are ethologically relevant in mammals. This is due to both production of local estrogens and signaling by these ligands, particularly in an interconnected set of nuclei called the social behavioural network (SBN). The SBN is a sexually dimorphic network studied predominantly in rodents that is thought to underlie the display of social behaviour in mammals.

Estrogenic regulation of social behavior and sexually dimorphic brain formation.

It has long been known that the estrogen, 17β-estradiol (17β-E), plays a central role for female reproductive physiology and behavior. Numerous studies have established the neurochemical and molecular basis of estrogenic induction of female sexual behavior, i.e.

Is the membrane estrogen receptor, GPER1, a promiscuous receptor that modulates nuclear estrogen receptor-mediated functions in the brain?

Contribution to Special Issue on Fast effects of steroids. Estrogen signals both slowly to regulate transcription and rapidly to activate kinases and regulate calcium levels. Both rapid, non-genomic signaling as well as genomic transcriptional signaling via intracellular estrogen receptors (ER)s can change behavior.

Membrane-initiated nuclear trafficking of the glucocorticoid receptor in hypothalamic neurons.

Glucocorticoid binding to the intracellular glucocorticoid receptor (GR) stimulates the translocation of the GR from the cytosol to the nucleus, which leads to the transactivation or transrepression of gene transcription. However, multiple lines of evidence suggest that glucocorticoid signaling can also be initiated from the plasma membrane. Here, we provide evidence for membrane-initiated glucocorticoid signaling by a membrane-impermeant dexamethasone-bovine serum albumin (Dex-BSA) conjugate, which induced GR nuclear trafficking in hypothalamic neurons in vitro and in vivo.

GPER1/GPR30 in the brain: Crosstalk with classical estrogen receptors and implications for behavior.

The GPER1/GPR30 is a membrane estrogen receptor (mER) that binds 17β-estradiol (17β-E) with high affinity and is thought to play a role in cancer progression and cardiovascular health. Though widespread in the central nervous system, less is known about this receptor's function in the brain. GPER1 has been shown to activate kinase cascades and calcium flux within cells rapidly, thus fitting in with the idea of being a mER that mediates non-genomic signaling by estrogens.

Detection of the Phosphorylation of the Estrogen Receptor α as an Outcome of GPR30 Activation.

Phosphorylation of the serine residues in estrogen receptor (ER) α is important in transcriptional activation. Hence, methods to detect such posttranslational modification events are valuable. We describe, in detail, the analysis of the phosphorylated ERα by electrophoretic separation of proteins and subsequent immuno-blotting techniques.

Membrane-initiated non-genomic signaling by estrogens in the hypothalamus: cross-talk with glucocorticoids with implications for behavior.

The estrogen receptor and glucocorticoid receptor are members of the nuclear receptor superfamily that can signal using both non-genomic and genomic transcriptional modes. Though genomic modes of signaling have been well characterized and several behaviors attributed to this signaling mechanism, the physiological significance of non-genomic modes of signaling has not been well understood. This has partly been due to the controversy regarding the identity of the membrane ER (mER) or membrane GR (mGR) that may mediate rapid, non-genomic signaling and the downstream signaling cascades that may result as a consequence of steroid ligands binding the mER or the mGR.

Activation of the GPR30 receptor promotes lordosis in female mice.

Background/aims: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways.

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice.

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17β estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improve spatial memory, suggesting that GPR30 plays a role in hippocampal-dependent cognition.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats.

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the α or β isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment.

Thyroid hormones regulate anxiety in the male mouse.

Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) α and β isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions.

Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice.

The GPR30, a former orphan GPCR, is a putative membrane estrogen receptor that can activate rapid signaling pathways such as extracellular regulated kinase (ERK) in a variety of cells and may contribute to estrogen's effects in the central nervous system. The distribution of GPR30 in the limbic system predicts a role for this receptor in the regulation of learning and memory and anxiety by estrogens. Though acute G-1 treatment is reported to be anxiogenic in ovariectomised female mice and in gonadally intact male mice, the effect of GPR30 activation is unknown in gonadectomised male mice.

Estrogen receptor-mediated transcription involves the activation of multiple kinase pathways in neuroblastoma cells.

While many physiological effects of estrogens (E) are due to regulation of gene transcription by liganded estrogen receptors (ERs), several effects are also mediated, at least in part, by rapid non-genomic actions of E. Though the relative importance of rapid versus genomic effects in the central nervous system is controversial, we showed previously that membrane-limited effects of E, initiated by an estradiol bovine serum albumin conjugate (E2-BSA), could potentiate transcriptional effects of 17β-estradiol from an estrogen response element (ERE)-reporter in neuroblastoma cells. Here, using specific inhibitors and activators in a pharmacological approach, we show that activation of phosphatidylinositol-3-phosphate kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways, dependent on a Gαq coupled receptor signaling are important in this transcriptional potentiation.

Distinct behavioral phenotypes in male mice lacking the thyroid hormone receptor α1 or β isoforms.

Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity.

Non-genomic actions of estrogens and their interaction with genomic actions in the brain.

Ligands for the nuclear receptor superfamily have at least two mechanisms of action: (a) classical transcriptional regulation of target genes (genomic mechanisms); and (b) non-genomic actions, which are initiated at the cell membrane, which could also impact transcription. Though transcriptional mechanisms are increasingly well understood, membrane-initiated actions of these ligands are incompletely understood. This has led to considerable debate over the physiological relevance of membrane-initiated actions of hormones versus genomic actions of hormones, with genomic actions predominating in the endocrine field.