Recognition of granulocyte-macrophage colony-stimulating factor by specific S100 proteins.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca2+-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca2+-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy. Of them, only S100A4 protein specifically binds to GM-CSF with equilibrium dissociation constant, Kd, values of 0.3-2 µM, as confirmed by intrinsic fluorescence and chemical crosslinking data. Calcium removal prevents S100A4 binding to GM-CSF, whereas monomerization of S100A4/A6/P proteins disrupts S100A4/A6 interaction with GM-CSF and induces a slight decrease in S100P affinity for GM-CSF. Structural modelling indicates the presence in the GM-CSF molecule of a conserved S100A4/A6/P-binding site, consisting of the residues from its termini, helices I and III, some of which are involved in the interaction with GM-CSF receptors. The predicted involvement of the 'hinge' region and F89 residue of S100P in GM-CSF recognition was confirmed by mutagenesis. Examination of S100A4/A6/P ability to affect GM-CSF signaling showed that S100A4/A6 inhibit GM-CSF-induced suppression of viability of monocytic THP-1 cells. The ability of the S100 proteins to modulate GM-CSF activity is relevant to progression of various neoplasms and other diseases, according to bioinformatics analysis. The direct regulation of GM-CSF signaling by extracellular forms of the S100 proteins should be taken into account in the clinical use of GM-CSF and development of the therapeutic interventions targeting GM-CSF or its receptors.

REC protein family expansion by the emergence of a new signaling pathway.

IMPORTANCE: We explore when and why large classes of proteins expand into new sequence space. We used an unsupervised machine learning approach to observe the sequence landscape of REC domains of bacterial response regulator proteins. We find that within-gene recombination can switch effector domains and, consequently, change the regulatory context of the duplicated protein.

Interaction of S100A6 Protein with the Four-Helical Cytokines.

S100 is a family of over 20 structurally homologous, but functionally diverse regulatory (calcium/zinc)-binding proteins of vertebrates. The involvement of S100 proteins in numerous vital (patho)physiological processes is mediated by their interaction with various (intra/extra)cellular protein partners, including cell surface receptors. Furthermore, recent studies have revealed the ability of specific S100 proteins to modulate cell signaling via direct interaction with cytokines. Previously, we revealed the binding of ca. 71% of the four-helical cytokines via the S100P protein, due to the presence in its molecule of a cytokine-binding site overlapping with the binding site for the S100P receptor. Here, we show that another S100 protein, S100A6 (that has a pairwise sequence identity with S100P of 35%), specifically binds numerous four-helical cytokines. We have studied the affinity of the recombinant forms of 35 human four-helical cytokines from all structural families of this fold to Ca2+-loaded recombinant human S100A6, using surface plasmon resonance spectroscopy. S100A6 recognizes 26 of the cytokines from all families of this fold, with equilibrium dissociation constants from 0.3 nM to 12 µM. Overall, S100A6 interacts with ca. 73% of the four-helical cytokines studied to date, with a selectivity equivalent to that for the S100P protein, with the differences limited to the binding of interleukin-2 and oncostatin M. The molecular docking study evidences the presence in the S100A6 molecule of a cytokine-binding site, analogous to that found in S100P. The findings argue the presence in some of the promiscuous members of the S100 family of a site specific to a wide range of four-helical cytokines. This unique feature of the S100 proteins potentially allows them to modulate the activity of the numerous four-helical cytokines in the disorders accompanied by an excessive release of the cytokines.

Experimental and Theoretical Studies of Hydrogen Storage in LaNi4.4Al0.3Fe0.3 Hydride Bed.

In this article, the experimental measurements of the absorption/desorption P-C-T isotherms of hydrogen in the LaNi4.4Fe0.3Al0.3 alloy at different temperatures and constant hydrogen pressure have been studied using a numerical model. The mathematics equations of this model contain parameters, such as the two terms, nα and nß, representing the numbers of hydrogen atoms per site; Nmα and Nmß are the receptor sites' densities, and the energetic parameters are Pα and Pß. All these parameters are derived by numerically adjusting the experimental data. The profiles of these parameters during the absorption/desorption process are studied as a function of temperature. Thereafter, we examined the evolution of the internal energy versus temperature, which typically ranges between 138 and 181 kJmol-1 for the absorption process and between 140 and 179 kJmol-1 for the desorption process. The evolution of thermodynamic functions with pressure, for example, entropy, Gibbs free energy (G), and internal energy, are determined from the experimental data of the hydrogen absorption and desorption isotherms of the LaNi4.4Al0.3Fe0.3 alloy.

New drugs and stock market: a machine learning framework for predicting pharma market reaction to clinical trial announcements.

Pharmaceutical companies operate in a strictly regulated and highly risky environment in which a single slip can lead to serious financial implications. Accordingly, the announcements of clinical trial results tend to determine the future course of events, hence being closely monitored by the public. Most works focus on retrospective analysis of announcement impact on company stock prices, bypassing the consideration of the problem in the predictive paradigm. In this work, we aim to close this gap by proposing a framework that allows predicting the numerical values of announcement-induced changes in stock prices. In fact, it is a problem of the impact prediction of the specific event on the corresponding time series. Our framework includes a BERT model for extracting the sentiment polarity of announcements, a Temporal Fusion Transformer for forecasting the expected return, a graph convolution network for capturing event relationships, and gradient boosting for predicting the price change. We operate with one of the biggest FDA (the Food and Drug Administration) datasets, consisting of 5436 clinical trial announcements from 681 companies for the years 2018-2022. During the study, we get several significant outcomes and domain-specific insights. Firstly, we obtain statistical evidence for the clinical result promulgation influence on the public pharma market value. Secondly, we witness inherently different patterns of responses to positive and negative announcements, reflected in a stronger and more pronounced reaction to negative clinical news. Thirdly, we discover two factors that play a crucial role in a predictive framework: (1) the drug portfolio size of the company, indicating the greater susceptibility to an announcement in the case of low diversification among drug products and (2) the announcement network effect, manifesting through an increase in predictive power when exploiting interdependencies of events belonging to the same company or nosology. Finally, we prove the viability of the forecast setting by getting ROC AUC scores predominantly greater than 0.7 for the classification of price change on historical data. We emphasize the transferability and generalizability of the developed framework on other datasets and domains but on the condition of the presence of two key entities: events and the associated time series.

Machine learning-based detection of cardiovascular disease using ECG signals: performance vs. complexity.

Introduction: Cardiovascular disease remains a significant problem in modern society. Among non-invasive techniques, the electrocardiogram (ECG) is one of the most reliable methods for detecting cardiac abnormalities. However, ECG interpretation requires expert knowledge and it is time-consuming. Developing a novel method to detect the disease early improves the quality and efficiency of medical care. Methods: The paper presents various modern approaches for classifying cardiac diseases from ECG recordings. The first approach suggests the Poincaré representation of ECG signal and deep-learning-based image classifiers. Additionally, the raw signals were processed with the one-dimensional convolutional model while the XGBoost model was facilitated to predict based on the time-series features. Results: The Poincaré-based methods showed decent performance in predicting AF (atrial fibrillation) but not other types of arrhythmia. XGBoost model gave an acceptable performance in long-term data but had a long inference time due to highly-consuming calculations within the pre-processing phase. Finally, the 1D convolutional model, specifically the 1D ResNet, showed the best results in both studied CinC 2017 and CinC 2020 datasets, reaching the F1 score of 85% and 71%, respectively, and they were superior to the first-ranking solution of each challenge. The 1D models also presented high specificity. Additionally, our paper investigated efficiency metrics including power consumption and equivalent CO2 emissions, with one-dimensional models like 1D CNN and 1D ResNet being the most energy efficient. Model interpretation analysis showed that the DenseNet detected AF using heart rate variability while the 1D ResNet assessed the AF patterns in raw ECG signals. Discussion: Despite the under-performed results, the Poincaré diagrams are still worth studying further because of the accessibility and inexpensive procedure. In the 1D convolutional models, the residual connections are useful to keep the model simple but not decrease the performance. Our approach in power measurement and model interpretation helped understand the numerical complexity and mechanism behind the model decision.

Attractor-repeller collision and the heterodimensional dynamics.

We study the heterodimensional dynamics in a simple map on a three-dimensional torus. This map consists of a two-dimensional driving Anosov map and a one-dimensional driven Möbius map, and demonstrates the collision of a chaotic attractor with a chaotic repeller if parameters are varied. We explore this collision by following tangent bifurcations of the periodic orbits and establish a regime where periodic orbits with different numbers of unstable directions coexist in a chaotic set. For this situation, we construct a heterodimensional cycle connecting these periodic orbits. Furthermore, we discuss properties of the rotation number and of the nontrivial Lyapunov exponent at the collision and in the heterodimensional regime.

Evaluation of the specificity of an intradermal test with recombinant tuberculosis allergen in Bacillus Calmette-Guérin-vaccinated healthy volunteers.

Introduction: The tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of Mycobacterium tuberculosis of the RDI region, which is absent in the genome of Mycobacterium bovis BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen [RTA (Diaskintest®, JSC Generium, Russia)]. Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test. Study objective: To assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis. Methods: A multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18-30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: [Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days)]. All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068). Results: In individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92-99%) with a cut-off of >0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94-100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test. Conclusion: Diaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.

Kinetics of Ca2+ Dissociation from Cod Parvalbumin Studied by Fluorescent Stopped-flow Method.

BACKGROUND: Small Ca2+-binding protein parvalbumin possesses two strong Ca2+/Mg2+- binding sites located within two EF-hand domains. Most parvalbumins have no tryptophan residues, while cod protein contains a single tryptophan residue, which fluorescence (spectrum maximum position and fluorescence quantum yield) is highly sensitive to the Ca2+ association/dissociation. OBJECTIVE: Intrinsic protein fluorescence of cod parvalbumin can be used for elucidating the mechanism of Ca2+ binding to this protein. Fluorescence of the single tryptophan residue of cod parvalbumin has been used to monitor Ca2+-induced changes in the protein, both in steady-state and kinetic mode. METHODS: Steady-state fluorescence spectra of cod parvalbumin were measured using Cary Eclipse spectrofluorimeter. Stopped-flow accessories in combination with a novel high-speed spectrofluorimeter were used for measurements of kinetics of Ca2+ dissociation from cod parvalbumin after fast mixing of Ca2+-loaded protein with a chelator of divalent metal cations ethylenediaminetetraacetic acid (EDTA). RESULTS: The fluorescent phase plots (fluorescence intensity at a fixed wavelength plotted against a fluorescence intensity at another fixed wavelength), constructed from steady state and kinetical data, shows a break at [Ca2+]/[parvalbumin] ratio close to 1. This means that the transition passes through an intermediate state, which is a protein with one bound calcium ion. These observations indicate that the binding of Ca2+ to cod parvalbumin is sequential. CONCLUSION: The results of the present spectral study showed that the binding of Ca2+ to cod parvalbumin is a sequential process. Calcium dissociation rate constants for the two binding sites of cod parvalbumin evaluated from the kinetic data are koff1 = 1.0 s-1 and koff2 = 1.5 s-1.

Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations.

A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing ß-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500-1500 kDa. Using various structural-analysis methods, we investigated in vitro nonspecific amyloid aggregation of the high-molecular-weight isoform of chicken smooth-muscle titin (SMTHMW, ~1500 kDa). As confirmed by X-ray diffraction analysis, under near-physiological conditions, the protein formed amorphous amyloid aggregates with a quaternary cross-ß structure within a relatively short time (~60 min). As shown by circular dichroism and Fourier-transform infrared spectroscopy, the quaternary cross-ß structure-unlike other amyloidogenic proteins-formed without changes in the SMTHMW secondary structure. SMTHMW aggregates partially disaggregated upon increasing the ionic strength above the physiological level. Based on the data obtained, it is not the complete protein but its particular domains/segments that are likely involved in the formation of intermolecular interactions during SMTHMW amyloid aggregation. The discovered properties of titin position this protein as an object of interest for studying amyloid aggregation in vitro and expanding our views of the fundamentals of amyloidogenesis.

Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.

Redox Regulation of Signaling Complex between Caveolin-1 and Neuronal Calcium Sensor Recoverin.

Caveolin-1 is a cholesterol-binding scaffold protein, which is localized in detergent-resistant membrane (DRM) rafts and interacts with components of signal transduction systems, including visual cascade. Among these components are neuronal calcium sensors (NCSs), some of which are redox-sensitive proteins that respond to calcium signals by modulating the activity of multiple intracellular targets. Here, we report that the formation of the caveolin-1 complex with recoverin, a photoreceptor NCS serving as the membrane-binding regulator of rhodopsin kinase (GRK1), is a redox-dependent process. Biochemical and biophysical in vitro experiments revealed a two-fold decreased affinity of recoverin to caveolin-1 mutant Y14E mimicking its oxidative stress-induced phosphorylation of the scaffold protein. At the same time, wild-type caveolin-1 demonstrated a 5-10-fold increased affinity to disulfide dimer of recoverin (dRec) or its thiol oxidation mimicking the C39D mutant. The formation of dRec in vitro was not affected by caveolin-1 but was significantly potentiated by zinc, the well-known mediator of redox homeostasis. In the MDCK cell model, oxidative stress indeed triggered Y14 phosphorylation of caveolin-1 and disulfide dimerization of recoverin. Notably, oxidative conditions promoted the accumulation of phosphorylated caveolin-1 in the plasma membrane and the recruitment of recoverin to the same sites. Co-localization of these proteins was preserved upon depletion of intracellular calcium, i.e., under conditions reducing membrane affinity of recoverin but favoring its interaction with caveolin-1. Taken together, these data suggest redox regulation of the signaling complex between recoverin and caveolin-1. During oxidative stress, the high-affinity interaction of thiol-oxidized recoverin with caveolin-1/DRMs may disturb the light-induced translocation of the former within photoreceptors and affect rhodopsin desensitization.

Calcium-Bound S100P Protein Is a Promiscuous Binding Partner of the Four-Helical Cytokines.

S100 proteins are multifunctional calcium-binding proteins of vertebrates that act intracellularly, extracellularly, or both, and are engaged in the progression of many socially significant diseases. Their extracellular action is typically mediated by the recognition of specific receptor proteins. Recent studies indicate the ability of some S100 proteins to affect cytokine signaling through direct interaction with cytokines. S100P was shown to be the S100 protein most actively involved in interactions with some four-helical cytokines. To assess the selectivity of the S100P protein binding to four-helical cytokines, we have probed the interaction of Ca2+-bound recombinant human S100P with a panel of 32 four-helical human cytokines covering all structural families of this fold, using surface plasmon resonance spectroscopy. A total of 22 cytokines from all families of four-helical cytokines are S100P binders with the equilibrium dissociation constants, Kd, ranging from 1 nM to 3 µM (below the Kd value for the S100P complex with the V domain of its conventional receptor, receptor for advanced glycation end products, RAGE). Molecular docking and mutagenesis studies revealed the presence in the S100P molecule of a cytokine-binding site, which overlaps with the RAGE-binding site. Since S100 binding to four-helical cytokines inhibits their signaling in some cases, the revealed ability of the S100P protein to interact with ca. 71% of the four-helical cytokines indicates that S100P may serve as a poorly selective inhibitor of their action.

On the origin of chaotic attractors with two zero Lyapunov exponents in a system of five biharmonically coupled phase oscillators.

We study chaotic dynamics in a system of four differential equations describing the interaction of five identical phase oscillators coupled via biharmonic function. We show that this system exhibits strange spiral attractors (Shilnikov attractors) with two zero (indistinguishable from zero in numerics) Lyapunov exponents in a wide region of the parameter space. We explain this phenomenon by means of bifurcation analysis of a three-dimensional Poincaré map for the system under consideration. We show that chaotic dynamics develop here near a codimension three bifurcation, when a periodic orbit (fixed point of the Poincaré map) has the triplet of multipliers ( 1 , 1 , 1 ). As it is known, the flow normal form for such bifurcation is the well-known three-dimensional Arneodó-Coullet-Spiegel-Tresser (ACST) system, which exhibits spiral attractors. According to this, we conclude that the additional zero Lyapunov exponent for orbits in the observed attractors appears due to the fact that the corresponding three-dimensional Poincaré map is very close to the time-shift map of the ACST-system.

Ibuprofen Favors Binding of Amyloid-ß Peptide to Its Depot, Serum Albumin.

The deposition of amyloid-ß peptide (Aß) in the brain is a critical event in the progression of Alzheimer's disease (AD). This Aß deposition could be prevented by directed enhancement of Aß binding to its natural depot, human serum albumin (HSA). Previously, we revealed that specific endogenous ligands of HSA improve its affinity to monomeric Aß. We show here that an exogenous HSA ligand, ibuprofen (IBU), exerts the analogous effect. Plasmon resonance spectroscopy data evidence that a therapeutic IBU level increases HSA affinity to monomeric Aß40/Aß42 by a factor of 3-5. Using thioflavin T fluorescence assay and transmission electron microcopy, we show that IBU favors the suppression of Aß40 fibrillation by HSA. Molecular docking data indicate partial overlap between the IBU/Aß40-binding sites of HSA. The revealed enhancement of the HSA-Aß interaction by IBU and the strengthened inhibition of Aß fibrillation by HSA in the presence of IBU could contribute to the neuroprotective effects of the latter, previously observed in mouse and human studies of AD.

Interferon-ß Activity Is Affected by S100B Protein.

Interferon-ß (IFN-ß) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-ß activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-ß interacts with one more representative of the S100 protein family, the S100B protein, involved in numerous oncological and neurological diseases. The use of chemical crosslinking, intrinsic fluorescence, and surface plasmon resonance spectroscopy revealed IFN-ß binding to Ca2+-loaded dimeric and monomeric forms of the S100B protein. Calcium depletion blocks the S100B-IFN-ß interaction. S100B monomerization increases its affinity to IFN-ß by 2.7 orders of magnitude (equilibrium dissociation constant of the complex reaches 47 pM). Crystal violet assay demonstrated that combined application of IFN-ß and S100B (5-25 nM) eliminates their inhibitory effects on MCF-7 cell viability. Bioinformatics analysis showed that the direct modulation of IFN-ß activity by the S100B protein described here could be relevant to progression of multiple oncological and neurological diseases.

Erythropoietin Interacts with Specific S100 Proteins.

Erythropoietin (EPO) is a clinically significant four-helical cytokine, exhibiting erythropoietic, cytoprotective, immunomodulatory, and cancer-promoting activities. Despite vast knowledge on its signaling pathways and physiological effects, extracellular factors regulating EPO activity remain underexplored. Here we show by surface plasmon resonance spectroscopy, that among eighteen members of Ca2+-binding proteins of the S100 protein family studied, only S100A2, S100A6 and S100P proteins specifically recognize EPO with equilibrium dissociation constants ranging from 81 nM to 0.5 µM. The interactions occur exclusively under calcium excess. Bioinformatics analysis showed that the EPO-S100 interactions could be relevant to progression of neoplastic diseases, including cancer, and other diseases. The detailed knowledge of distinct physiological effects of the EPO-S100 interactions could favor development of more efficient clinical implications of EPO. Summing up our data with previous findings, we conclude that S100 proteins are potentially able to directly affect functional activities of specific members of all families of four-helical cytokines, and cytokines of other structural superfamilies.

Specific cytokines of interleukin-6 family interact with S100 proteins.

Cytokines of interleukin-6 (IL-6) family are important signaling proteins involved in various physiological and pathological processes. Earlier, we described interactions between IL-11 and S100P/B proteins from the family of S100 proteins engaged in the pathogenesis of numerous diseases. We probed here interactions between seven IL-6 family cytokines (IL-6, IL-11, OSM, LIF, CNTF, CT-1, and CLCF1) and fourteen S100 proteins (S100A1/A4/A6/A7/A8/A9/A10/A11/A12/A13/A14/A15/B/P). Surface plasmon resonance spectroscopy revealed formation of calcium-dependent complexes between IL-11, OSM, CNTF, CT-1, and CLCF1 and distinct subsets of S100A1/A6/B/P proteins with equilibrium dissociation constants of 19 nM - 12 µM. The existence of a network of interactions between Ca2+-loaded S100 proteins and IL-6 family cytokines suggest regulation of these cytokines by the extracellular forms of S100 proteins.

Conjoined Lorenz twins-a new pseudohyperbolic attractor in three-dimensional maps and flows.

We describe new types of Lorenz-like attractors for three-dimensional flows and maps with symmetries. We give an example of a three-dimensional system of differential equations, which is centrally symmetric and mirror symmetric. We show that the system has a Lorenz-like attractor, which contains three saddle equilibrium states and consists of two mirror-symmetric components that are adjacent at the symmetry plane. We also found a discrete-time analog of this "conjoined-twins" attractor in a cubic three-dimensional Hénon map with a central symmetry. We show numerically that both attractors are pseudohyperbolic, which guarantees that each orbit of the attractor has a positive maximal Lyapunov exponent, and this property is preserved under small perturbations. We also describe bifurcation scenarios for the emergence of the attractors in one-parameter families of three-dimensional flows and maps possessing the symmetries.