scholarly journals Physiological Network From Anthropometric and Blood Test Biomarkers

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonio Barajas-Martínez ◽  
Elizabeth Ibarra-Coronado ◽  
Martha Patricia Sierra-Vargas ◽  
Ivette Cruz-Bautista ◽  
Paloma Almeda-Valdes ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Medical Knowledge ◽  
Structural Features ◽  
Experimental Conditions ◽  
Correlation Matrices ◽  
Detection Algorithms ◽  
Physiological Variables ◽  
Topological Features ◽  
Network Connectedness ◽  
Living Organisms

Currently, research in physiology focuses on molecular mechanisms underlying the functioning of living organisms. Reductionist strategies are used to decompose systems into their components and to measure changes of physiological variables between experimental conditions. However, how these isolated physiological variables translate into the emergence -and collapse- of biological functions of the organism as a whole is often a less tractable question. To generate a useful representation of physiology as a system, known and unknown interactions between heterogeneous physiological components must be taken into account. In this work we use a Complex Inference Networks approach to build physiological networks from biomarkers. We employ two unrelated databases to generate Spearman correlation matrices of 81 and 54 physiological variables, respectively, including endocrine, mechanic, biochemical, anthropometric, physiological, and cellular variables. From these correlation matrices we generated physiological networks by selecting a p-value threshold indicating statistically significant links. We compared the networks from both samples to show which features are robust and representative for physiology in health. We found that although network topology is sensitive to the p-value threshold, an optimal value may be defined by combining criteria of stability of topological features and network connectedness. Unsupervised community detection algorithms allowed to obtain functional clusters that correlate well with current medical knowledge. Finally, we describe the topology of the physiological networks, which lie between random and ordered structural features, and may reflect system robustness and adaptability. Modularity of physiological networks allows to explore functional clusters that are consistent even when considering different physiological variables. Altogether Complex Inference Networks from biomarkers provide an efficient implementation of a systems biology approach that is visually understandable and robust. We hypothesize that physiological networks allow to translate concepts such as homeostasis into quantifiable properties of biological systems useful for determination and quantification of health and disease.

scholarly journals Experimental diagenesis: insights into aragonite to calcite transformation of <i>Arctica islandica</i> shells by hydrothermal treatment

2017 ◽  
Vol 14 (6) ◽  
pp. 1461-1492 ◽  
Author(s):  
Laura A. Casella ◽  
Erika Griesshaber ◽  
Xiaofei Yin ◽  
Andreas Ziegler ◽  
Vasileios Mavromatis ◽  
...  
Keyword(s):  
Hydrothermal Alteration ◽  
Fossil Record ◽  
Marine Invertebrates ◽  
Structural Features ◽  
Geochemical Data ◽  
Replacement Reaction ◽  
Bulk Analysis ◽  
Arctica Islandica ◽  
Experimental Conditions ◽  
Living Organisms

Abstract. Biomineralised hard parts form the most important physical fossil record of past environmental conditions. However, living organisms are not in thermodynamic equilibrium with their environment and create local chemical compartments within their bodies where physiologic processes such as biomineralisation take place. In generating their mineralised hard parts, most marine invertebrates produce metastable aragonite rather than the stable polymorph of CaCO3, calcite. After death of the organism the physiological conditions, which were present during biomineralisation, are not sustained any further and the system moves toward inorganic equilibrium with the surrounding inorganic geological system. Thus, during diagenesis the original biogenic structure of aragonitic tissue disappears and is replaced by inorganic structural features. In order to understand the diagenetic replacement of biogenic aragonite to non-biogenic calcite, we subjected Arctica islandica mollusc shells to hydrothermal alteration experiments. Experimental conditions were between 100 and 175 °C, with the main focus on 100 and 175 °C, reaction durations between 1 and 84 days, and alteration fluids simulating meteoric and burial waters, respectively. Detailed microstructural and geochemical data were collected for samples altered at 100 °C (and at 0.1 MPa pressure) for 28 days and for samples altered at 175 °C (and at 0.9 MPa pressure) for 7 and 84 days. During hydrothermal alteration at 100 °C for 28 days most but not the entire biopolymer matrix was destroyed, while shell aragonite and its characteristic microstructure was largely preserved. In all experiments up to 174 °C, there are no signs of a replacement reaction of shell aragonite to calcite in X-ray diffraction bulk analysis. At 175 °C the replacement reaction started after a dormant time of 4 days, and the original shell microstructure was almost completely overprinted by the aragonite to calcite replacement reaction after 10 days. Newly formed calcite nucleated at locations which were in contact with the fluid, at the shell surface, in the open pore system, and along growth lines. In the experiments with fluids simulating meteoric water, calcite crystals reached sizes up to 200 µm, while in the experiments with Mg-containing fluids the calcite crystals reached sizes up to 1 mm after 7 days of alteration. Aragonite is metastable at all applied conditions. Only a small bulk thermodynamic driving force exists for the transition to calcite. We attribute the sluggish replacement reaction to the inhibition of calcite nucleation in the temperature window from ca. 50 to ca. 170 °C or, additionally, to the presence of magnesium. Correspondingly, in Mg2+-bearing solutions the newly formed calcite crystals are larger than in Mg2+-free solutions. Overall, the aragonite–calcite transition occurs via an interface-coupled dissolution–reprecipitation mechanism, which preserves morphologies down to the sub-micrometre scale and induces porosity in the newly formed phase. The absence of aragonite replacement by calcite at temperatures lower than 175 °C contributes to explaining why aragonitic or bimineralic shells and skeletons have a good potential of preservation and a complete fossil record.

Effects of Provocation on Emotions and Aggression: An Experimental Study with Aggressive Children

2006 ◽  
Vol 65 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Christina Stadler ◽  
Sonja Rohrmann ◽  
Sibylle Steuber ◽  
Fritz Poustka
Keyword(s):  
Experimental Study ◽  
Positive Emotions ◽  
Skin Conductance Level ◽  
Physiological Measures ◽  
Competitive Reaction ◽  
Experimental Conditions ◽  
Conduct Disordered ◽  
Physiological Variables ◽  
Aggressive Children ◽  
Conductance Level

In this study, the effects of an experimental-induced provocation on emotions and aggression were examined in 34 aggressive conduct-disordered children using a competitive reaction time paradigm. Two experimental conditions were created, an increasing provocation and a low constant provocation condition. Self-rated anger was assessed directly after provocation on a 5-point-visual scale. In addition, negative and positive emotions as well as physiological measures (heart rate and skin conductance level) were measured at baseline and after provocation. Results revealed that participants’ aggressive behaviour and subjective emotions differed as a function of the opponent’s level of provocation. Concerning physiological parameters, no significant differences were found between the experimental conditions. These results suggest that affective, but not physiological variables characterize reactive aggression in conduct-disordered children.

Effects of Fear Induction on Heart Period Variability

1999 ◽  
Vol 13 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Rudolf Stark ◽  
Alfons Hamm ◽  
Anne Schienle ◽  
Bertram Walter ◽  
Dieter Vaitl
Keyword(s):  
Blood Pressure ◽  
Trait Anxiety ◽  
State Anxiety ◽  
Self Report ◽  
Emotional States ◽  
Heart Period ◽  
Experimental Conditions ◽  
Heart Period Variability ◽  
Physiological Variables ◽  
Period Variability

Abstract The present study investigated the influence of contextual fear in comparison to relaxation on heart period variability (HPV), and analyzed differences in HPV between low and high anxious, nonclinical subjects. Fifty-three women participated in the study. Each subject underwent four experimental conditions (control, fear, relaxation, and a combined fear-relaxation condition), lasting 10 min each. Fear was provoked by an unpredictable aversive human scream. Relaxation should be induced with the aid of verbal instructions. To control for respiratory effects on HPV, breathing was paced at 0.2 Hz using an indirect light source. Besides physiological measures (HPV measures, ECG, respiration, forearm EMG, blood pressure), emotional states (pleasure, arousal, dominance, state anxiety) were assessed by subjects' self-reports. Since relaxation instructions did not have any effect neither on the subjective nor on the physiological variables, the present paper focuses on the comparison of the control and the fear condition. The scream reliably induced changes in both physiological and self-report measures. During the fear condition, subjects reported more arousal and state anxiety as well as less pleasure and dominance. Heart period decreased, while EMG and diastolic blood pressure showed a tendency to increase. HPV remained largely unaltered with the exception of the LF component, which slightly decreased under fear induction. Replicating previous findings, trait anxiety was negatively associated with HPV, but there were no treatment-specific differences between subjects with low and high trait anxiety.

scholarly journals Biophysical characterization of melanoma cell phenotype markers during metastatic progression

2021 ◽  
Author(s):  
Anna Sobiepanek ◽  
Alessio Paone ◽  
Francesca Cutruzzolà ◽  
Tomasz Kobiela
Keyword(s):  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Structural Features ◽  
Protein Glycosylation ◽  
Cell Phenotype ◽  
Metastatic Progression ◽  
Label Free ◽  
Serine Threonine Kinase ◽  
Biophysical Characterization ◽  
Viscoelastic Parameters

AbstractMelanoma is the most fatal form of skin cancer, with increasing prevalence worldwide. The most common melanoma genetic driver is mutation of the proto-oncogene serine/threonine kinase BRAF; thus, the inhibition of its MAP kinase pathway by specific inhibitors is a commonly applied therapy. However, many patients are resistant, or develop resistance to this type of monotherapy, and therefore combined therapies which target other signaling pathways through various molecular mechanisms are required. A possible strategy may involve targeting cellular energy metabolism, which has been recognized as crucial for cancer development and progression and which connects through glycolysis to cell surface glycan biosynthetic pathways. Protein glycosylation is a hallmark of more than 50% of the human proteome and it has been recognized that altered glycosylation occurs during the metastatic progression of melanoma cells which, in turn facilitates their migration. This review provides a description of recent advances in the search for factors able to remodel cell metabolism between glycolysis and oxidative phosphorylation, and of changes in specific markers and in the biophysical properties of cells during melanoma development from a nevus to metastasis. This development is accompanied by changes in the expression of surface glycans, with corresponding changes in ligand-receptor affinity, giving rise to structural features and viscoelastic parameters particularly well suited to study by label-free biophysical methods.

scholarly journals Unusual Structural Features in the Adduct of Dirhodium Tetraacetate with Lysozyme

2021 ◽  
Vol 22 (3) ◽  
pp. 1496
Author(s):  
Domenico Loreto ◽  
Giarita Ferraro ◽  
Antonello Merlino
Keyword(s):  
Anticancer Agents ◽  
Structural Features ◽  
Side Chain ◽  
Side Chains ◽  
Valuable Insight ◽  
Experimental Conditions ◽  
Egg White Lysozyme ◽  
Potential Applications ◽  
Model Protein ◽  
Hen Egg White

The structures of the adducts formed upon reaction of the cytotoxic paddlewheel dirhodium complex [Rh2(μ-O2CCH3)4] with the model protein hen egg white lysozyme (HEWL) under different experimental conditions are reported. Results indicate that [Rh2(μ-O2CCH3)4] extensively reacts with HEWL:it in part breaks down, at variance with what happens in reactions with other proteins. A Rh center coordinates the side chains of Arg14 and His15. Dimeric Rh–Rh units with Rh–Rh distances between 2.3 and 2.5 Å are bound to the side chains of Asp18, Asp101, Asn93, and Lys96, while a dirhodium unit with a Rh–Rh distance of 3.2–3.4 Å binds the C-terminal carboxylate and the side chain of Lys13 at the interface between two symmetry-related molecules. An additional monometallic fragment binds the side chain of Lys33. These data, which are supported by replicated structural determinations, shed light on the reactivity of dirhodium tetracarboxylates with proteins, providing useful information for the design of new Rh-containing biomaterials with an array of potential applications in the field of catalysis or of medicinal chemistry and valuable insight into the mechanism of action of these potential anticancer agents.

scholarly journals The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected by small molecule inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lucia Silvestrini ◽  
Norhan Belhaj ◽  
Lucia Comez ◽  
Yuri Gerelli ◽  
Antonino Lauria ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Dissociation Constant ◽  
Molecular Mechanisms ◽  
Antiviral Drug ◽  
Structural Features ◽  
Experimental Information ◽  
Detailed Knowledge ◽  
Main Protease ◽  
Equilibrium Dissociation ◽  
Drug Leads

AbstractThe maturation of coronavirus SARS-CoV-2, which is the etiological agent at the origin of the COVID-19 pandemic, requires a main protease Mpro to cleave the virus-encoded polyproteins. Despite a wealth of experimental information already available, there is wide disagreement about the Mpro monomer-dimer equilibrium dissociation constant. Since the functional unit of Mpro is a homodimer, the detailed knowledge of the thermodynamics of this equilibrium is a key piece of information for possible therapeutic intervention, with small molecules interfering with dimerization being potential broad-spectrum antiviral drug leads. In the present study, we exploit Small Angle X-ray Scattering (SAXS) to investigate the structural features of SARS-CoV-2 Mpro in solution as a function of protein concentration and temperature. A detailed thermodynamic picture of the monomer-dimer equilibrium is derived, together with the temperature-dependent value of the dissociation constant. SAXS is also used to study how the Mpro dissociation process is affected by small inhibitors selected by virtual screening. We find that these inhibitors affect dimerization and enzymatic activity to a different extent and sometimes in an opposite way, likely due to the different molecular mechanisms underlying the two processes. The Mpro residues that emerge as key to optimize both dissociation and enzymatic activity inhibition are discussed.

scholarly journals Computational Modeling to Explain Why 5,5-Diarylpentadienamides are TRPV1 Antagonists

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1765
Author(s):  
Julio Caballero
Keyword(s):  
Transient Receptor Potential ◽  
Structural Information ◽  
Chemical Activation ◽  
Receptor Potential ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Transient Receptor Potential Vanilloid ◽  
Protein Residues ◽  
Topological Features ◽  
Transient Receptor

Several years ago, the crystallographic structures of the transient receptor potential vanilloid 1 (TRPV1) in the presence of agonists and antagonists were reported, providing structural information about its chemical activation and inactivation. TRPV1’s activation increases the transport of calcium and sodium ions, leading to the excitation of sensory neurons and the perception of pain. On the other hand, its antagonistic inactivation has been explored to design analgesic drugs. The interactions between the antagonists 5,5-diarylpentadienamides (DPDAs) and TRPV1 were studied here to explain why they inactivate TRPV1. The present work identified the structural features of TRPV1–DPDA complexes, starting with a consideration of the orientations of the ligands inside the TRPV1 binding site by using molecular docking. After this, a chemometrics analysis was performed (i) to compare the orientations of the antagonists (by using LigRMSD), (ii) to describe the recurrent interactions between the protein residues and ligand groups in the complexes (by using interaction fingerprints), and (iii) to describe the relationship between topological features of the ligands and their differential antagonistic activities (by using a quantitative structure–activity relationship (QSAR) with 2D autocorrelation descriptors). The interactions between the DPDA groups and the residues Y511, S512, T550, R557, and E570 (with a recognized role in the binding of classic ligands), and the occupancy of isoquinoline or 3-hydroxy-3,4-dihydroquinolin-2(1H)-one groups of the DPDAs in the vanilloid pocket of TRPV1 were clearly described. Based on the results, the structural features that explain why DPDAs inactivate TRPV1 were clearly exposed. These features can be considered for the design of novel TRPV1 antagonists.

scholarly journals Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Codruţa Şoica ◽  
Mirela Voicu ◽  
Roxana Ghiulai ◽  
Cristina Dehelean ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Active Role ◽  
Structural Features ◽  
Sex Hormone ◽  
Ongoing Research ◽  
New Treatment ◽  
Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

scholarly journals Molecular mechanisms associated with clustered lesion-induced impairment of 8-oxoG recognition by the human glycosylase OGG1

2021 ◽  
Author(s):  
Tao Jiang ◽  
Antonio MONARI ◽  
Elise Dumont ◽  
Emmanuelle Bignon
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Structural Features ◽  
Repair Pathway ◽  
Dna Lesion ◽  
Damage Response ◽  
Base Excision ◽  
Structural Signature ◽  
Dynamics Simulations

The 8-oxo-7,8-dihydroguanine, referred to as 8-oxoG, is a highly mutagenic DNA lesion that can provoke the appearance of mismatches if it escapes the DNA Damage Response. The specific recognition of its structural signature by the hOGG1 glycosylase is the first step along the Base Excision Repair pathway, that ensures the integrity of the genome by preventing the emergence of mutations. 8-oxoG formation, structural features and repair have been the matter of extensive research and more recently this active field of research expended to the more complicated case of 8-oxoG within clustered lesions. Indeed, the presence of a second lesion within 1 or 2 helix turns can dramatically impact the repair yields of 8-oxoG by glycosylases. In this work, we use mu-range molecular dynamics simulations and machine learning-based post-analysis to explore the molecular mechanisms associated with the recognition of 8-oxoG by hOGG1 when embedded in a multiple lesions site with a mismatch in 5' or 3'. We delineate the stiffening of the DNA-protein interactions upon the presence of the mismatches, and rationalize the much lower repair yields reported with a 5' mismatch by describing the perturbation of 8-oxoG structural features upon addition of an adjacent lesion.

Potential Health Benefits Of A Pomegranate Extract, Rich In Phenolic Compounds, In Intestinal Inflammation

2021 ◽  
Vol 17 ◽  
Author(s):  
Marco Raffaele ◽  
Khaled Greish ◽  
Luca Vanella ◽  
Giuseppe Carota ◽  
Fatemah Bahman ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Marker ◽  
Experimental Models ◽  
Cellular Damage ◽  
Experimental Conditions ◽  
Potential Health

Background: Pomegranate is a fruit rich in bioactive compounds such as punicalagins, gallic acid, and ellagic acid derivatives. It has been widely used since ancient times in traditional medicine for a wide variety of diseases. It has been reported that bioactive compounds, such as polyphenols, are able to induce the expression of cytoprotective enzymes, including HO-1. The contribution of HO-1 activity to the prevention of intestinal inflammation has been shown in different models of Inflammatory bowel diseases (IBD). Objective: Aim of the present research was to investigate the molecular mechanisms involved in the beneficial effects of a pomegranate extract (PE), rich in bioactive compounds in intestinal inflammation. Methods: Caco-2 cells exposed to LPS and DSS induced colitis were chosen as convenient experimental models of intestinal inflammation. Results: Results obtained in our experimental conditions, showed that PE in vitro was able to induce HO-1 and to reduce cellular damage and oxidative stress through increase of GSH levels. Moreover, PE was able to decrease the pro-inflammatory marker IL-8 levels and to activate TIGAR pathway. The results obtained in vivo, in agreement with the data obtained in vitro, highlighted the ability of PE to reduce intestinal inflammation, preserve the colon length and histological features and reduce IL-6 levels compared to the DSS treated group. Conclusion: PE, rich in bioactive compounds, could contribute, as supportive therapy, to enhance the effects of the conventional therapeutic strategies to the management of IBD.

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