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The outbreak of coronavirus disease 2019 (COVID-19) due to its highly virulent nature has created a health crisis worldwide. It has attracted biologists’ attention to understand the morphology, host-pathogen interaction and signalling cascade at the core level. The whole world has come to a standstill due to the contagious nature and transmission rate of this virus. To understand the risk of COVID-19 outbreak across different parts of the globe it is crucial to provide a mechanistic framework for the interrelation of comorbidities. This review chapter focuses on the characteristic features, signalling cascade, and the interplay between pathogenesis and unfolded protein response in coronavirus. Due to the complexity of the coronavirus genome and its replication cycle, our understanding of structural, non-structural and accessory proteins in virion assembly and involvement of host machinery is significant. Thus, there is an urgent need to develop effective antiviral doses and vaccines against coronavirus. Hence, updating the detailed mechanism of cross-talk between virus and host, signal and receptor and the evasion of cellular innate immune responses is of utmost importance to develop novel therapeutic strategies.

The cGAS–STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS–STING pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS–STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS–STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS–STING signalling cascade and discuss the general mechanisms underlying the association of cGAS–STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications., The cGAS–STING pathway drives innate immune activation in response to cytosolic DNA. This is important for immunity to bacteria and viruses, but aberrant cGAS–STING activity is also linked to inflammatory disease. Here, Ablasser and colleagues discuss how cGAS–STING signalling contributes to various autoimmune, inflammatory and degenerative diseases and describe the novel therapeutics targeting this pathway.

Nitrogen (N) is a central mineral nutrient essential for plant development and growth. It is usually scarcely found in soils, so the knowledge of the overall plant N metabolism deserves substantial attention. Polyamines (PAs) are N-containing low-molecular-weight compounds of polycationic nature involved in essential processes all throughout the life of plants whereas nitric oxide (NO) is a gaseous free radical involved in signalling cascades related to many physiological events. PAs and NO share signalling functions and interact with each other in several biological functions, mainly in stress responses. Biosynthesis pathways of PAs and NO are overlapped; PAs induce NO formation, but it is still not completely defined whether PAs act as substrates, cofactors, or signals for promoting NO synthesis and also, which are the mechanisms involved in NO regulation of PAs metabolism. Polyamine levels are of vital importance in the regulation of the network of N-metabolising pathways in plants, as they are components of the core of the overall N metabolism. In light of the importance of improving the efficiency of N uptake and distribution, it is time to elucidate the intricate relationship among N as a nutrient with PAs and NO as emerging signalling molecules. The close cooperation among these players in the whole N metabolism is an interesting target for the development of biotechnological tools for sustainable agriculture. Fil: Recalde, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Gómez Mansur, Nabila María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Cabrera, Andrea Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Matayoshi, Carolina Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Gallego, Susana Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Groppa, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Benavides, Maria Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina

Increased use of nitrogen fertilizers has deleterious impact on the environment. Increase in yield potential at low nitrogen supply is regarded as a cereal breeding goal for future agricultural sustainability. Although natural variations of nitrogen transporters have been investigated, key genes associated with assimilation remain largely unexplored for nitrogen use efficiency (NUE) enhancement. Here, we identified a NIN‐like protein NLP4 associated with NUE through a GWAS in rice. We found that OsNLP4 transactivated OsNiR encoding nitrite reductase that was critical in nitrogen assimilation in rice. We further constructed quadrupling NREs (Nitrate‐responsive cis‐elements) in the promoter of OsNiR (p4xNRE:OsNiR) and enhanced nitrogen assimilation significantly. We demonstrated that OsNLP4‐OsNiR increased tiller number and yield through enhancing nitrogen assimilation and NUE. Our discovery highlights the genetic modulation of OsNLP4‐OsNiR signalling cascade as a strategy for high NUE and yield breeding in rice.

Graphene is a novel, sp2 carbon atoms bonded, two-dimensional nano-material. Due to their favorable electronic, thermal, optical, and mechanical property, graphene and its derivatives, like graphene oxide (GO) and graphene quantum dots (GQDs) are used in widespread applications. The outstanding potentials of these compounds in the field of nanoelectronics, composite materials, sensors, energy technology etc helped in the rapid development in their functionalization, modulatory effects on various systems of our body. GQDs has been suggested as a new nanomaterial with improved biocompatibility, biodegradability, water solubility and considerably low cytotoxic effects in in vivo models, and are applicable for altering immune responses based on quantum confinement and edge effect properties. The review particularly elucidates the mechanistic approach by which graphene and/ or its derivatives and/ or their nano-compound aid in therapeutic management against myriads of immunological perspectives. GQDs have unique physiochemical properties with carbon sheets showcases out-standing biological response against immunological interventions by altering the activities of t-cell lymphocytes. On the contrary GO plays a vital role in eliciting inflammatory signaling factors by controlling proinflammation and an anti-inflammatory response. Therefore, this review shall help the readers to have an overview of the biomedical application of graphene and its derivatives to design target specific drugs to regulate the immune response based prognosis andcure.

The RNA-binding protein LARP1 has generated interest in recent years for its role in the mTOR signalling cascade and its regulation of terminal oligopyrimidine (TOP) mRNA translation. Paradoxically, some scientists have shown that LARP1 represses TOP translation while others that LARP1 activates it. Here, we present opinions from four leading scientists in the field to discuss these and other contradictory findings.

The terrestrial environment is complex, with many parameters fluctuating on daily and seasonal basis. Plants in particular, have developed complex sensory and signalling networks to extract and integrate information about their surroundings, in order to maximise their fitness and mitigate some of the detrimental effects of their sessile lifestyles. Light and temperature each provide crucial insight on the surrounding environment and in combination allow plants to appropriately develop, grow and adapt. Crosstalk between light and temperature signalling cascades allow plants to time key developmental decisions accordingly to ensure they are “in sync” with their environment. In this review, we discuss the major players that regulate light and temperature signalling, and the cross‐talk between them, in reference to a crucial developmental decision faced by plants: to bloom or not to bloom?

Gallbladder cancer (GBC) has a poor prognosis with a 5-year survival rate suggesting the need for more effective treatment strategies. Studying the cross-talk of several pathways involved in crucial cellular and biological processes such as cell growth, proliferation, migration and apoptosis would prove beneficial in identifying key players of GBC progression and targeting them. This review highlights several pathways known to be dysregulated in GBC onset and progression and describes known and potential targets. Within these pathways, there are proteins involved in the signalling cascade, which may be targeted as potential biomarkers and drug targets. Furthermore, the cross-talk of these pathways is investigated in the context of GBC and the implications thereof. A better understanding of the pathways involved in GBC pathogenesis will aid clinicians in the prognosis, diagnosis and treatment of patients. There are significant clinical implications of GBC pathway-based studies as they permit the understanding of onset and progression of the disease.

This review presents a molecular framework for how phytohormones regulate normal root hair development and how this is affected by changes in the rhizosphere, to enable greater understanding of the specialized functions of root hairs and their developmental and environmental plasticity., The main functions of plant roots are water and nutrient uptake, soil anchorage, and interaction with soil-living biota. Root hairs, single cell tubular extensions of root epidermal cells, facilitate or enhance these functions by drastically enlarging the absorptive surface. Root hair development is constantly adapted to changes in the root’s surroundings, allowing for optimization of root functionality in heterogeneous soil environments. The underlying molecular pathway is the result of a complex interplay between position-dependent signalling and feedback loops. Phytohormone signalling interconnects this root hair signalling cascade with biotic and abiotic changes in the rhizosphere, enabling dynamic hormone-driven changes in root hair growth, density, length, and morphology. This review critically discusses the influence of the major plant hormones on root hair development, and how changes in rhizosphere properties impact on the latter.

A chemically-triggered signalling cascade between cucurbituril host-guest complexes by means of multi-step competitive displacement is demonstrated. The inter-complex communication of chemical information yields the release of bio-relevant cargo, reminiscent of cellular signalling pathways.

Purpose of Review: Opioids are administered to cancer patients although concerns have been raised that they may promote tumour growth or metastasis owing to their ability to suppress anti-cancer immunity. Tramadol has been reported to preserve or promote the immune response and may therefore be preferred to other opioids in cancer patients. We reviewed the literature documenting the immunomodulatory effects of tramadol. Recent Findings: Recent clinical evidence appears to confirm that tramadol possesses anti-inflammatory properties, and preserves some signalling cascades of the immune system relevant to anti-cancer defence. Summary: Tramadol is reported to promote or preserve immunity including natural killer cell activity which is important in anti-cancer defences.

Diet bioactive components, in the concept of nutrigenetics and nutrigenomics, consist of food constituents, which can transfer information from the external environment and influence gene expression in the cell and thus the function of the whole organism. It is crucial to regard food not only as the source of energy and basic nutriments, crucial for living and organism development, but also as the factor influencing health/disease, biochemical mechanisms, and activation of biochemical pathways. Bioactive components of the diet regulate gene expression through changes in the chromatin structure (including DNA methylation and histone modification), non-coding RNA, activation of transcription factors by signalling cascades, or direct ligand binding to the nuclear receptors. Analysis of interactions between diet components and human genome structure and gene activity is a modern approach that will help to better understand these relations and will allow designing dietary guidances, which can help maintain good health.

3′,5′-Cyclic guanosine monophosphate (cGMP) is one of the major second messengers critically involved in the regulation of cardiac electrophysiology, hypertrophy, and contractility. Recent molecular and cellular studies have significantly advanced our understanding of the cGMP signalling cascade, its local microdomain-specific regulation and its role in protecting the heart from pathological stress. Here, we summarise recent findings on cardiac cGMP microdomain regulation and discuss their potential clinical significance.

The effective treatment of many diseases requires the use of multiple treatment strategies among which neuromodulation is playing an increasingly important role. Neuromodulation devices that act to normalize or modulate nerve activity through the targeted delivery of electrical stimuli will be the focus of this review. These devices encompass deep brain stimulators, vagus nerve stimulators, spinal cord simulators and sacral nerve stimulators. Already neuromodulation has proven successful in the treatment of a broad range of conditions from Parkinson's disease to chronic pain and urinary incontinence. Many of these approaches seek to exploit the activities of the autonomic nervous system, which influences organ function through the release of neurotransmitters and associated signalling cascades. This review will outline existing and emerging applications for each of these neuromodulation devices, proposed mechanisms of action and clinical studies evaluating both their safety and therapeutic efficacy.

Plants continuously rely on light as an energy source and as the driver of many processes in their lifetimes. The ability to perceive different light radiations involves several photoreceptors, which in turn activate complex signalling cascades that ultimately lead to a rearrangement in plant metabolism as an adaptation strategy towards specific light conditions. This review, after a brief summary of the structure and mode of action of the different photoreceptors, introduces the main classes of secondary metabolites and specifically focuses on the influence played by the different wavelengths on the content of these compounds in agricultural plants, because of their recognised roles as nutraceuticals.

Type 2 diabetes has been a global health challenge over the decades and is among the leading causes of death. Several treatment approaches have been developed, but more effective and new therapies are still needed. The role of adenosine in glucose and lipid homeostasis has offered a different therapeutic approach. Adenosine mediates its physiological role through the activation of adenosine receptors. These adenosine receptors have been implicated in glucose and lipid homeostasis. The ability of agonists and antagonists of adenosine receptors to activate or inhibit the adenosine signalling cascade and thereby affecting the balance of glucose and lipid homeostasis has challenged the studies of agonists and antagonists of adenosine receptors, both preclinical and clinical, as potential anti-diabetic drugs. This review provides a background on different anti-diabetic therapeutic approaches, outlining the role of adenosine receptors in glucose and lipid homeostasis, and mechanisms underlying the action of agonists/antagonists of adenosine receptors as a therapeutic potential towards type 2 diabetes.

Host immune activation forms a vital line of defence against bacterial pathogenicity. However, just as hosts have evolved immune responses, bacteria have developed means to escape, hijack and subvert these responses to promote survival. In recent years, a highly conserved group of signalling cascades within the host, collectively termed the integrated stress response (ISR), have become increasingly implicated in immune activation during bacterial infection. Activation of the ISR leads to a complex web of cellular reprogramming, which ultimately results in the paradoxical outcomes of either cellular homeostasis or cell death. Therefore, any pathogen with means to manipulate this pathway could induce a range of cellular outcomes and benefit from favourable conditions for long-term survival and replication. This review aims to outline what is currently known about bacterial manipulation of the ISR and present key hypotheses highlighting areas for future research.

Purpose of review The aim of this study was to summarize recent findings about the role of the epidermal growth factor receptor (EGFR) in acute kidney injury and in progression of chronic kidney injury. Recent findings There is increasing evidence that EGFR activation occurs as a response to either ischemic or toxic kidney injury and EGFR signalling plays an important role in recovery of epithelial integrity. However, with incomplete recovery or in conditions predisposing to progressive glomerular and tubulointerstitial injury, aberrant persistent EGFR signalling is a causal mediator of progressive fibrotic injury. New studies have implicated activation of HIPPO/YAP signalling as a component of EGFR's actions in the kidney. There is also new evidence for sex disparities in kidney EGFR expression and activation after injury, with a male predominance that is mediated by androgens. Summary There is increasing evidence for an important role for EGFR signalling in mediation of kidney injury, raising the possibility that interruption of the signalling cascade could limit progression of development of progressive kidney fibrosis.

Plants are at the interface of above- and below-ground interactions. The diverse group of microbes interacts with the plants in both beneficial and detrimental manner. Plants have evolved a number of different strategies to overcome these attacks. Viruses make an important group of organisms that interact with the plant to use the host molecular machinery to replicate its own genome and propagate further. Plants have developed defence strategies involving electrical signalling, using reactive oxygen species and involve the role of different plant hormones in a signalling cascade. This prevents the plant from further damage and also intimates its neighbouring plant to prepare themselves for a forthcoming attack. Volatile organic compounds play an important role in such phenomenon.

A new paper reports that the protein isthmin 1 is secreted by mature adipocytes and triggers a signalling cascade similar to that of insulin. The novel adipokine acts through an unidentified receptor tyrosine kinase and, at pharmacological doses in mice, isthmin 1 ameliorates metabolic disturbances associated with type 2 diabetes mellitus, including hyperglycaemia and liver steatosis.

An evolutionarily ancient plant hormone receptor complex comprising the α/β-fold hydrolase receptor KARRIKIN INSENSITIVE 2 (KAI2) and the F-box protein MORE AXILLARY GROWTH 2 (MAX2) mediates a range of developmental responses to smoke-derived butenolides called karrikins (KARs) and to yet elusive endogenous KAI2 ligands (KLs). Degradation of SUPPRESSOR OF MAX2 1 (SMAX1) after ligand perception is considered to be a key step in KAR/KL signaling. However, molecular events which regulate plant development downstream of SMAX1 removal have not been identified. Here we show that Lotus japonicus SMAX1 is specifically degraded in the presence of KAI2 and MAX2 and plays an important role in regulating root and root hair development. smax1 mutants display very short primary roots and elongated root hairs. Their root transcriptome reveals elevated ethylene responses and expression of ACC Synthase 7 (ACS7), which encodes a rate-limiting enzyme in ethylene biosynthesis. smax1 mutants release increased amounts of ethylene and their root phenotype is rescued by treatment with ethylene biosynthesis and signaling inhibitors. KAR treatment induces ACS7 expression in a KAI2-dependent manner and root developmental responses to KAR treatment depend on ethylene signaling. Furthermore, in Arabidopsis, KAR-induced root hair elongation depends on ACS7. Thus, we reveal a connection between KAR/KL and ethylene signaling in which the KAR/KL signaling module (KAI2–MAX2–SMAX1) regulates the biosynthesis of ethylene to fine-tune root and root hair development, which are important for seedling establishment at the beginning of the plant life cycle.

At the surface of many cells is a compendium of glycoconjugates that form an interface between the cell and its surroundings; the glycocalyx. The glycocalyx serves several functions that have captivated the interest of many groups. Given its privileged residence, this meshwork of sugar-rich biomolecules is poised to transmit signals across the cellular membrane, facilitating communication with the extracellular matrix and mediating important signalling cascades. As a product of the glycan biosynthetic machinery, the glycocalyx can serve as a partial mirror that reports on the cell's glycosylation status. The glycocalyx can also serve as an information-rich barrier, withholding the entry of pathogens into the underlying plasma membrane through glycan-rich molecular messages. In this review, we provide an overview of the different approaches devised to engineer glycans at the cell surface, highlighting considerations of each, as well as illuminating the grand challenges that face the next era of ‘glyco-engineers’. While we have learned much from these techniques, it is evident that much is left to be unearthed.

Proteins are key player in the prognosis and therapeutics of carcinomas through the interactions of downstream signalling cascades. Current work insight the structural and mutational analysis of DACH1 in association with carcinogenesis. The homology modelling was employed to predict mutant and wild protein models and their reliability and accuracy was verified through multiple online approaches. Furthermore, MD simulation technique was employed to check the mutation effects on the stability of DACH1 through root mean square deviation and fluctuation graphs. Our results proposed that DACH1 mutation (C188Y) may cause lethal effects and can disturb the DACH1 structure. The observed mutational results showed that C188Y may cause some lethal effect in human body. Based on aforementioned computational assessments, it has concluded that DACH1 could be used as good therapeutic target in the prognosis and therapeutic of carcinoma insurgence.Communicated by Ramaswamy H. Sarma.

It is hypothesised that the inhibition of the non-canonical Wnt/PCP intracellular signalling cascade by potato glycoalkaloids, [Formula: see text]-solanine and [Formula: see text]-chaconine, results in an increased risk of neural tube defects (NTDs). One very prominent intracellular signalling pathway with substantial implications in the development and closure of the neural tube is the Wnt/PCP pathway. Experimental inhibition of this results in NTDs. A vital element of this signalling cascade is JNK, which controls the transcription of DNA, which controls cell polarity and directional cell migration. JNK inhibition also results in NTDs experimentally. Through their use in cancer research, [Formula: see text]-solanine and [Formula: see text]-chaconine were found to inhibit metastasis by inhibiting JNK, among other intracellular signalling molecules. Thus, this shows that potato glycoalkaloids increase the likelihood of causing NTDs by inhibiting the proper functioning of JNK in the Wnt/PCP pathway, resulting in defective neural tube closure.

INTRODUCTION: Endometriosis is common gynaecological disorder that leads to infertility in females of reproductive age. It is characterized by endometrial glands and stromal tissues outside the wall of uterus. Upregulation of estradiol is responsible for the cell proliferation, adhesion and invasion in endometriosis. It enhances prostaglandins (PGE-2) that triggers the formation of matrix metalloproteinases (MMPs), Tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-kB). Whereas, levels of progesterone are reported to be decreased in the patients with endometriosis. Less production of progesterone activity of 17β-hydroxysteroid dehydrogenase-II (17β-HSD-II) decreases that converts estradiol to less potent estrone. Intake of excess trans-fats and deficiency of vitamin D raises level of arachidonic acid and converts PGE-2 by the action cyclooxygenase (COX-2). PGE2 in theca cells of ovaries increases cAMP and activity of liver receptor homologue-1/steroidogenic factor-1(LRH-1/SF-1) thus leading to the stimulation of aromatase enzyme. MATERIALS AND METHODS: Two hundred eighty-eight (n=288) females with endometriosis and hundred (n=100) controls were enrolled. Informed consent was obtained before the collection of samples. Levels of estradiol, progesterone, aromatase enzymes, 17β-HSD-II, COX-2, PGE-2, MMPs (2, 7, 9), vitamin D and lipopolysaccharides (LPO) were estimated by respective protocols. RESULTS: Findings suggests significant increase in the levels of estradiol, aromatase enzymes, COX-2, PGE-2, MMPs (2,7,9) and LPO (67.08±5.55 pg/ml, 7.16±1.28 ng/ml, 1.56±0.144 ng/ml, 4.89±0.61 pg/ml, 995.2±8.15 ng/ml, 105.2±7.19 ng/ml, 109.2±12.25 ng/ml and 125.25±11.26 pg/ml) in patients as compared to (21.08±3.65 pg/ml, 2.08±0.15 ng/ml, 0.61±0.056 ng/ml, 1.158±0.18 pg/ml, 388.26±14.26 ng/ml, 66.29±5.26 ng/ml, 38.29±15.2 ng/ml and 17.25±1.26 pg/ml) controls respectively. Whereas, levels of progesterone, 17β-HSD-II and vitamin D remained significantly low in the endometrial patients (3.07±1.08 ng/ml, 0.183±0.024 ng/ml and 17.17±2.3 ng/ml) as compared to healthy females (29.22±3.29 ng/ml, 1.43±0.153 ng/ml and 36.26±3.09 ng/ml). CONCLUSION: Current study suggests the role of estradiol in triggering ECM degradation and initiating signalling cascades that following a feedback loop enhances the levels of estradiol and contributes in the development and progression of endometriosis. Hence, therapies with supplementation of vitamin D and progesterone may help in regressing the role estradiol and other contributing factors that are involved in the development and progression of endometriosis in the patients. Keyword: Endometrial glands, Stromal tissues, Estrogen, Progesterone, Endometriosis, Vitamin D

In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions.

Cold stress is a significant threat for plant productivity and impacts on plant distribution and crop production, particularly so when it occurs during the growth phase. A developmental stage at risk is that of flowering, since a single stress event during sensitive stages, such as the full-bloom stage of fruit trees can be fatal for reproductive success. Although pollen development and fertilization are widely viewed as the most critical reproductive phases, the development and function of female reproductive tissues, which in Angiosperms are embedded in the gynoecium, are also affected by cold stress. Today however, we have essentially no understanding of the cold stress response pathways that act during floral organogenesis. In this review, we briefly summarize our current knowledge of cold stress signalling modules active in vegetative tissues that may provide a framework of general principles also transferable to female reproductive tissues. We then align these signalling cascades with those that govern gynoecium development to identify factors that may act in both processes and could thereby contribute to cold stress responses in female reproductive tissues.

Two sets of reactants for modelling neurogenesis (SRMN) were developed based on the designed and tested genetic structures of lentiviral vectors. SRMN-1 contains the genetic construct LVV-GFAP-GCaMP3 and is intended for cellspecific transduction in astroglia cells. SRMN-2 contains the genetic construct LVV-PRSx8-TN-XXL and is intended for the phenotype-specific transduction in neurons. The present study examined SRMN-1 and SRMN-2 samples and assessed their efficiency in vitro and in vivo in Norvegicus rats. Specificity to particular cell types for all SRMN samples exceeded 97%. The number of induced signalling cascades was determined via activation of intracellular ingsignalling cascades in neurons and astrocytes (purinergic receptors and β-adrenoceptors). The results demonstrated dynamic recording of fluorescent signals and a two-fold increase in intensity after addition of the activator in all samples. The experimental SRMN samples revealed successful and stable transfection of catecholaminergic neurons and astrocytes, data on transfection efficiency, specificity of the developed genetic structures of SRMN, and calcium dynamics in transfected neurons and astrocytes. These results confirm the crucial role of astrocytes in ensuring neurogenesis. The results in pure cell culture (in vitro) were identical to the in vivo results in animals.

To achieve their reproductive potential, barnacles combine tactile exploration of surface structural properties and integration of cellular signals originating from their antennular sensory setae within a developmentally defined, temporally narrow window of settlement opportunity. Behavioural assays with cyprids coupled with biometric analysis of scanning electron microscopy-acquired images in the presence of specific chemical compounds were used to investigate how settlement on a substratum is altered in response to the presence of these compounds. It is shown that impeding tactile exploration, altering cellular signalling and/or inducing malformations of anatomical features of the antennular sensory setae can disrupt the settlement behaviour of the model barnacle species Amphibalanus amphitrite. It is concluded that surface exploration by the cyprids relies on mechanical and nociception-related and calcium-mediated signals while a protein kinase C signalling cascade controls the timely metamorphosis of the cyprids to sessile juveniles.

In many eukaryotic signalling cascades, receptor-mediated phospholipase C (PLC) activity triggers phosphatidylinositol-4,5- bisphosphate (PIP2) hydrolysis, leading to information transfer. Coupled with PLC activation is a sequence of reactions spread across multiple compartments which resynthesize PIP2, a process essential for supporting sustained PLC signalling. The biochemical strategies coordinating these reactions and, in particular, whether this is a closed cycle with no net addition or loss of metabolites, are poorly understood. Using mathematical models, we find that most closed PIP2 cycles cannot explain experimentally observed changes in key metabolic intermediates in particular mutants. Thus, we propose that the PIP2 cycle likely includes at least one metabolic source and one sink whose net activity results in the experimentally observed regulation of this key signalling pathway.

The PI3K-AKT signalling cascade has a highly conserved role in a variety of processes including cell growth and glucose homoeostasis. Variants affecting this pathway can lead to one of several segmental overgrowth disorders. These conditions are genetically heterogeneous and require tailored, multidisciplinary involvement throughout life. Hypoglycaemia is common in other overgrowth syndromes but has been described only sporadically in association with PIK3CA and CCND2 variants. We report a cohort of 6 children with megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes who developed clinically significant hypoglycaemia. Based on our findings, we suggest that segmental overgrowth patients should be screened for low blood glucose levels during childhood and there should be early specialist endocrine review in any children who develop hypoglycaemia.