Exploring strategies for classification of external stimuli using statistical features of the plant electrical response

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this record.Plants sense their environment by producing electrical signals which in essence represent changes in underlying physiological processes. These electrical signals, when monitored, show both stochastic and deterministic dynamics. In this paper, we compute 11 statistical features from the raw non-stationary plant electrical signal time series to classify the stimulus applied (causing the electrical signal). By using different discriminant analysis-based classification techniques, we successfully establish that there is enough information in the raw electrical signal to classify the stimuli. In the process, we also propose two standard features which consistently give good classification results for three types of stimuli--sodium chloride (NaCl), sulfuric acid (H₂SO₄) and ozone (O₃). This may facilitate reduction in the complexity involved in computing all the features for online classification of similar external stimuli in future.The work reported in this paper was supported by project PLants Employed As SEnsor Devices (PLEASED), EC grant agreement number 296582

Forward and Inverse Modelling Approaches for Prediction of Light Stimulus from Electrophysiological Response in Plants

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In this paper, system identification approach has been adopted to develop a novel dynamical model for describing the relationship between light as an environmental stimulus and the electrical response as the measured output for a bay leaf (Laurus nobilis) plant. More specifically, the target is to predict the characteristics of the input light stimulus (in terms of on-off timing, duration and intensity) from the measured electrical response - leading to an inverse problem. We explored two major classes of system estimators to develop dynamical models - linear and nonlinear - and their several variants for establishing a forward and also an inverse relationship between the light stimulus and plant electrical response. The best class of models are given by the Nonlinear Hammerstein-Wiener (NLHW) estimator showing good data fitting results over other linear and nonlinear estimators in a statistical sense. Consequently, a few set of models using different functional variants of NLHW has been developed and their accuracy in detecting the on-off timing and intensity of the input light stimulus are compared for 19 independent plant datasets (including 2 additional species viz. Zamioculcas zamiifolia and Cucumis sativus) under similar experimental scenario.The work reported in this paper was supported by project PLants Employed As SEnsor Devices (PLEASED), EC grant agreement number 296582

The biogenesis of SARS-CoV-2 spike glycoprotein: multiple targets for host-directed antiviral therapy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 (coronavirus disease-19), represents a far more serious threat to public health than SARS and MERS coronaviruses, due to its ability to spread more efficiently than its predecessors. Currently, there is no worldwide-approved effective treatment for COVID-19, urging the scientific community to intense efforts to accelerate the discovery and development of prophylactic and therapeutic solutions against SARS-CoV-2 infection. In particular, effective antiviral drugs are urgently needed. With few exceptions, therapeutic approaches to combat viral infections have traditionally focused on targeting unique viral components or enzymes; however, it has now become evident that this strategy often fails due to the rapid emergence of drug-resistant viruses. Targeting host factors that are essential for the virus life cycle, but are dispensable for the host, has recently received increasing attention. The spike glycoprotein, a component of the viral envelope that decorates the virion surface as a distinctive crown ("corona") and is essential for SARS-CoV-2 entry into host cells, represents a key target for developing therapeutics capable of blocking virus invasion. This review highlights aspects of the SARS-CoV-2 spike biogenesis that may be amenable to host-directed antiviral targeting

The Zinc-Finger AN1-Type Domain 2a Gene Acts as a Regulator of Cell Survival in Human Melanoma: Role of E3-Ligase cIAP2

The zinc-finger AN1-type domain-2a gene, also known as AIRAP (arsenite-inducible RNA-associated protein), was initially described as an arsenite-inducible gene in Caenorhabditis elegans and mammalian cells. Differently from the AIRAP worm homologue, aip-1, a gene known to play an important role in preserving animal lifespan and buffering arsenic-induced proteotoxicity, mammals have a second, constitutively expressed, AIRAP-like gene (AIRAPL), recently implicated in myeloid transformation. We have identified human AIRAP as a canonical heat-shock gene, whose expression, differently from AIRAPL, is strictly dependent on the proteotoxic-stress regulator heat-shock factor 1 (HSF1). AIRAP function is still not well defined and there is no information on AIRAP in cancer. Herein we show that bortezomib and next-generation proteasome inhibitors ixazomib and carfilzomib markedly induce AIRAP expression in human melanoma at concentrations comparable to plasma-levels in treated patients. AIRAP-downregulation leads to bortezomib sensitization, whereas AIRAP-overexpression protects melanoma cells from the drug, identifying AIRAP as a novel HSF1-regulated marker of chemotherapy resistance. More importantly, this study unexpectedly revealed that, also in the absence of drugs, AIRAP-silencing hinders melanoma clonogenic potential and spheroid growth, promoting caspase activation and apoptotic cell death, an effect independent of AIRAPL and linked to downregulation of the antiapoptotic protein cIAP2. Interestingly, AIRAP was found to interact with cIAP2, regulating its stability in melanoma. Taken together, the results identify AIRAP as a novel HSF1-dependent regulator of prosurvival networks in melanoma cells, opening new therapeutic perspectives in chemoresistant melanoma treatment

Demo abstract: Plants as Sensing Devices: The PLEASED experience

In this paper we discuss the first results of the PLEASED project [1] which aims at employing plants as biosensors of a new generation of pervasive and organic wireless sensor networks

Dual targeting of JAK2 and ERK interferes with the myeloproliferative neoplasm clone and enhances therapeutic efficacy.

Myeloproliferative neoplasms (MPN) show dysregulated JAK2 signaling. JAK2 inhibitors provide clinical benefits, but compensatory activation of MAPK pathway signaling impedes efficacy. We hypothesized that dual targeting of JAK2 and ERK1/2 could enhance clone control and therapeutic efficacy. We employed genetic and pharmacologic targeting of ERK1/2 in Jak2V617F MPN mice, cells and patient clinical isolates. Competitive transplantations of Jak2V617F vs. wild-type bone marrow (BM) showed that ERK1/2 deficiency in hematopoiesis mitigated MPN features and reduced the Jak2V617F clone in blood and hematopoietic progenitor compartments. ERK1/2 ablation combined with JAK2 inhibition suppressed MAPK transcriptional programs, normalized cytoses and promoted clone control suggesting dual JAK2/ERK1/2 targeting as enhanced corrective approach. Combined pharmacologic JAK2/ERK1/2 inhibition with ruxolitinib and ERK inhibitors reduced proliferation of Jak2V617F cells and corrected erythrocytosis and splenomegaly of Jak2V617F MPN mice. Longer-term treatment was able to induce clone reductions. BM fibrosis was significantly decreased in MPLW515L-driven MPN to an extent not seen with JAK2 inhibitor monotherapy. Colony formation from JAK2V617F patients' CD34+ blood and BM was dose-dependently inhibited by combined JAK2/ERK1/2 inhibition in PV, ET, and MF subsets. Overall, we observed that dual targeting of JAK2 and ERK1/2 was able to enhance therapeutic efficacy suggesting a novel treatment approach for MPN