scholarly journals Dissipative structures in biological systems: bistability, oscillations, spatial patterns and waves

2018 ◽  
Vol 376 (2124) ◽  
pp. 20170376 ◽  
Author(s):  
Albert Goldbeter
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Periodic Structures ◽  
Biological Systems ◽  
Dissipative Structures ◽  
Turing Patterns ◽  
Biological Organization ◽  
Wide Range ◽  
Propagating Waves ◽  
Spatio Temporal

The goal of this review article is to assess how relevant is the concept of dissipative structure for understanding the dynamical bases of non-equilibrium self-organization in biological systems, and to see where it has been applied in the five decades since it was initially proposed by Ilya Prigogine. Dissipative structures can be classified into four types, which will be considered, in turn, and illustrated by biological examples: (i) multistability, in the form of bistability and tristability, which involve the coexistence of two or three stable steady states, or in the form of birhythmicity, which involves the coexistence between two stable rhythms; (ii) temporal dissipative structures in the form of sustained oscillations, illustrated by biological rhythms; (iii) spatial dissipative structures, known as Turing patterns; and (iv) spatio-temporal structures in the form of propagating waves. Rhythms occur with widely different periods at all levels of biological organization, from neural, cardiac and metabolic oscillations to circadian clocks and the cell cycle; they play key roles in physiology and in many disorders. New rhythms are being uncovered while artificial ones are produced by synthetic biology. Rhythms provide the richest source of examples of dissipative structures in biological systems. Bistability has been observed experimentally, but has primarily been investigated in theoretical models in an increasingly wide range of biological contexts, from the genetic to the cell and animal population levels, both in physiological conditions and in disease. Bistable transitions have been implicated in the progression between the different phases of the cell cycle and, more generally, in the process of cell fate specification in the developing embryo. Turing patterns are exemplified by the formation of some periodic structures in the course of development and by skin stripe patterns in animals. Spatio-temporal patterns in the form of propagating waves are observed within cells as well as in intercellular communication. This review illustrates how dissipative structures of all sorts abound in biological systems. This article is part of the theme issue ‘Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 1)’.

scholarly journals The problem of scale in the prediction and management of pathogen spillover

2019 ◽  
Vol 374 (1782) ◽  
pp. 20190224 ◽  
Author(s):  
Daniel J. Becker ◽  
Alex D. Washburne ◽  
Christina L. Faust ◽  
Erin A. Mordecai ◽  
Raina K. Plowright
Keyword(s):  
Large Scale ◽  
Plasmodium Knowlesi ◽  
Hendra Virus ◽  
Human Populations ◽  
Biological Organization ◽  
Spatial And Temporal Scales ◽  
Eastern Australia ◽  
Wide Range ◽  
Pathogen Discovery ◽  
Spatio Temporal

Disease emergence events, epidemics and pandemics all underscore the need to predict zoonotic pathogen spillover. Because cross-species transmission is inherently hierarchical, involving processes that occur at varying levels of biological organization, such predictive efforts can be complicated by the many scales and vastness of data potentially required for forecasting. A wide range of approaches are currently used to forecast spillover risk (e.g. macroecology, pathogen discovery, surveillance of human populations, among others), each of which is bound within particular phylogenetic, spatial and temporal scales of prediction. Here, we contextualize these diverse approaches within their forecasting goals and resulting scales of prediction to illustrate critical areas of conceptual and pragmatic overlap. Specifically, we focus on an ecological perspective to envision a research pipeline that connects these different scales of data and predictions from the aims of discovery to intervention. Pathogen discovery and predictions focused at the phylogenetic scale can first provide coarse and pattern-based guidance for which reservoirs, vectors and pathogens are likely to be involved in spillover, thereby narrowing surveillance targets and where such efforts should be conducted. Next, these predictions can be followed with ecologically driven spatio-temporal studies of reservoirs and vectors to quantify spatio-temporal fluctuations in infection and to mechanistically understand how pathogens circulate and are transmitted to humans. This approach can also help identify general regions and periods for which spillover is most likely. We illustrate this point by highlighting several case studies where long-term, ecologically focused studies (e.g. Lyme disease in the northeast USA, Hendra virus in eastern Australia, Plasmodium knowlesi in Southeast Asia) have facilitated predicting spillover in space and time and facilitated the design of possible intervention strategies. Such studies can in turn help narrow human surveillance efforts and help refine and improve future large-scale, phylogenetic predictions. We conclude by discussing how greater integration and exchange between data and predictions generated across these varying scales could ultimately help generate more actionable forecasts and interventions. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

Polyphyllin I Induces Cell Cycle Arrest and Cell Apoptosis in Human Retinoblastoma Y-79 Cells through Targeting p53

2018 ◽  
Vol 18 (6) ◽  
pp. 875-881 ◽  
Author(s):  
Xue Zhu ◽  
Ke Wang ◽  
Kai Zhang ◽  
Yi Pan ◽  
Fanfan Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Potential Effect ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
P53 Expression ◽  
Cycle Arrest ◽  
Wide Range ◽  
Human Retinoblastoma

Background: Retinoblastoma is the most common intraocular malignant tumor in childhood. Although external beam radiation and enucleation are effective to control retinoblastoma, eye salvage and vision preservation are still significant challenges. Polyphyllin I (PPI), a natural compound extracted from Paris polyphylla rhizomes, has a wide range of activities against many types of cancers. However, the potential effect of this herbal compound on retinoblastoma has not yet been investigated. Method: In the present study, we evaluated the cytotoxic effect of PPI on human retinoblastoma Y-79 cells as well as its underlying molecular mechanism. Our results indicated that PPI treatment significantly inhibited cell proliferation, arrested the cell cycle at G2/M phase and induced cell apoptosis of Y79 cells through the mitochondrial- dependent intrinsic pathway. Moreover, p53 is involved in PPI-induced cytotoxicity in human retinoblastoma Y-79 cells. Exposure to 10 μM PPI for 48 h dramatically induced the expression levels of p53, phosphorylated- p53 and acetylated-p53. Furthermore, blockade of p53 expression effectively attenuated PPI-induced cell cycle arrest and cell apoptosis in Y-79 cells. Result: These results demonstrated that PPI exhibits anti-proliferation effect on human retinoblastoma Y-79 cells through modulating p53 expression, stabilization and activation. This information shed light on the potential application of PPI in retinoblastoma therapy.

Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones

2019 ◽  
Vol 19 (9) ◽  
pp. 1132-1140
Author(s):  
Heba A.E. Mohamed ◽  
Hossa F. Al-Shareef
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cytotoxic Activities ◽  
Significant Group ◽  
Design Synthesis ◽  
Standard Drug ◽  
Wide Range

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Death ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Black Cumin ◽  
In Silico Docking ◽  
Wide Range

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

scholarly journals The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities

2021 ◽  
Vol 22 (13) ◽  
pp. 6857
Author(s):  
Samantha Bruno ◽  
Manuela Mancini ◽  
Sara De Santis ◽  
Cecilia Monaldi ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Cell Fate ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Bone Marrow Microenvironment ◽  
Metabolic Adaptation ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes.

scholarly journals Kinematic Analysis of Lower Limb Joint Asymmetry during Gait in People with Multiple Sclerosis

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 598
Author(s):  
Massimiliano Pau ◽  
Bruno Leban ◽  
Michela Deidda ◽  
Federica Putzolu ◽  
Micaela Porta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lower Limb ◽  
Sagittal Plane ◽  
Cross Sectional Study ◽  
Camera Motion ◽  
Cross Sectional ◽  
Temporal Parameters ◽  
Wide Range ◽  
Edss Score ◽  
Spatio Temporal

The majority of people with Multiple Sclerosis (pwMS), report lower limb motor dysfunctions, which may relevantly affect postural control, gait and a wide range of activities of daily living. While it is quite common to observe a different impact of the disease on the two limbs (i.e., one of them is more affected), less clear are the effects of such asymmetry on gait performance. The present retrospective cross-sectional study aimed to characterize the magnitude of interlimb asymmetry in pwMS, particularly as regards the joint kinematics, using parameters derived from angle-angle diagrams. To this end, we analyzed gait patterns of 101 pwMS (55 women, 46 men, mean age 46.3, average Expanded Disability Status Scale (EDSS) score 3.5, range 1–6.5) and 81 unaffected individuals age- and sex-matched who underwent 3D computerized gait analysis carried out using an eight-camera motion capture system. Spatio-temporal parameters and kinematics in the sagittal plane at hip, knee and ankle joints were considered for the analysis. The angular trends of left and right sides were processed to build synchronized angle–angle diagrams (cyclograms) for each joint, and symmetry was assessed by computing several geometrical features such as area, orientation and Trend Symmetry. Based on cyclogram orientation and Trend Symmetry, the results show that pwMS exhibit significantly greater asymmetry in all three joints with respect to unaffected individuals. In particular, orientation values were as follows: 5.1 of pwMS vs. 1.6 of unaffected individuals at hip joint, 7.0 vs. 1.5 at knee and 6.4 vs. 3.0 at ankle (p < 0.001 in all cases), while for Trend Symmetry we obtained at hip 1.7 of pwMS vs. 0.3 of unaffected individuals, 4.2 vs. 0.5 at knee and 8.5 vs. 1.5 at ankle (p < 0.001 in all cases). Moreover, the same parameters were sensitive enough to discriminate individuals of different disability levels. With few exceptions, all the calculated symmetry parameters were found significantly correlated with the main spatio-temporal parameters of gait and the EDSS score. In particular, large correlations were detected between Trend Symmetry and gait speed (with rho values in the range of –0.58 to –0.63 depending on the considered joint, p < 0.001) and between Trend Symmetry and EDSS score (rho = 0.62 to 0.69, p < 0.001). Such results suggest not only that MS is associated with significantly marked interlimb asymmetry during gait but also that such asymmetry worsens as the disease progresses and that it has a relevant impact on gait performances.

scholarly journals Engineering the Interface between Inorganic Nanoparticles and Biological Systems through Ligand Design

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1001
Author(s):  
Rui Huang ◽  
David C. Luther ◽  
Xianzhi Zhang ◽  
Aarohi Gupta ◽  
Samantha A. Tufts ◽  
...  
Keyword(s):  
Organic Synthesis ◽  
Molecular Design ◽  
Biological Systems ◽  
Ligand Design ◽  
Inorganic Nanoparticles ◽  
Organic Ligands ◽  
Biological Applications ◽  
Wide Range ◽  
Insight Into

Nanoparticles (NPs) provide multipurpose platforms for a wide range of biological applications. These applications are enabled through molecular design of surface coverages, modulating NP interactions with biosystems. In this review, we highlight approaches to functionalize nanoparticles with ”small” organic ligands (Mw < 1000), providing insight into how organic synthesis can be used to engineer NPs for nanobiology and nanomedicine.

scholarly journals Quantitative linear dichroism imaging of molecular processes in living cells made simple by open software tools

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alexey Bondar ◽  
Olga Rybakova ◽  
Josef Melcr ◽  
Jan Dohnálek ◽  
Petro Khoroshyy ◽  
...  
Keyword(s):  
Biological Systems ◽  
Linear Dichroism ◽  
Quantitative Information ◽  
Living Cells ◽  
Software Tools ◽  
Model Systems ◽  
Membrane Properties ◽  
Polarization Microscopy ◽  
Molecular Processes ◽  
Wide Range

AbstractFluorescence-detected linear dichroism microscopy allows observing various molecular processes in living cells, as well as obtaining quantitative information on orientation of fluorescent molecules associated with cellular features. Such information can provide insights into protein structure, aid in development of genetically encoded probes, and allow determinations of lipid membrane properties. However, quantitating and interpreting linear dichroism in biological systems has been laborious and unreliable. Here we present a set of open source ImageJ-based software tools that allow fast and easy linear dichroism visualization and quantitation, as well as extraction of quantitative information on molecular orientations, even in living systems. The tools were tested on model synthetic lipid vesicles and applied to a variety of biological systems, including observations of conformational changes during G-protein signaling in living cells, using fluorescent proteins. Our results show that our tools and model systems are applicable to a wide range of molecules and polarization-resolved microscopy techniques, and represent a significant step towards making polarization microscopy a mainstream tool of biological imaging.

scholarly journals HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaohong Zhou ◽  
Christina Monnie ◽  
Maria DeLucia ◽  
Jinwoo Ahn
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Cycle Arrest ◽  
Histone Deacetylase ◽  
E3 Ligase ◽  
Cycle Arrest ◽  
Wide Range ◽  
In Vitro Reconstitution ◽  
Hiv 1

Abstract Background Vpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1. Methods HEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein–protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting. Results We demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase, Conclusions Targeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether, our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.

scholarly journals A Novel Benzopyrane Derivative Targeting Cancer Cell Metabolic and Survival Pathways

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2840
Author(s):  
Dana M. Zaher ◽  
Wafaa S. Ramadan ◽  
Raafat El-Awady ◽  
Hany A. Omar ◽  
Fatema Hersi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cancer Cell ◽  
Xenograft Model ◽  
Mitochondrial Metabolism ◽  
High Dose ◽  
Anticancer Effect ◽  
Safety Margins ◽  
Wide Range

(1) Background: Today, the discovery of novel anticancer agents with multitarget effects and high safety margins represents a high challenge. Drug discovery efforts indicated that benzopyrane scaffolds possess a wide range of pharmacological activities. This spurs on building a skeletally diverse library of benzopyranes to identify an anticancer lead drug candidate. Here, we aim to characterize the anticancer effect of a novel benzopyrane derivative, aiming to develop a promising clinical anticancer candidate. (2) Methods: The anticancer effect of SIMR1281 against a panel of cancer cell lines was tested. In vitro assays were performed to determine the effect of SIMR1281 on GSHR, TrxR, mitochondrial metabolism, DNA damage, cell cycle progression, and the induction of apoptosis. Additionally, SIMR1281 was evaluated in vivo for its safety and in a xenograft mice model. (3) Results: SIMR1281 strongly inhibits GSHR while it moderately inhibits TrxR and modulates the mitochondrial metabolism. SIMR1281 inhibits the cell proliferation of various cancers. The antiproliferative activity of SIMR1281 was mediated through the induction of DNA damage, perturbations in the cell cycle, and the inactivation of Ras/ERK and PI3K/Akt pathways. Furthermore, SIMR1281 induced apoptosis and attenuated cell survival machinery. In addition, SIMR1281 reduced the tumor volume in a xenograft model while maintaining a high in vivo safety profile at a high dose. (4) Conclusions: Our findings demonstrate the anticancer multitarget effect of SIMR1281, including the dual inhibition of glutathione and thioredoxin reductases. These findings support the development of SIMR1281 in preclinical and clinical settings, as it represents a potential lead compound for the treatment of cancer.

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