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System biology

Ana Rita Araujo, Lendert Gelens, Rahuman S M Sheriff, Silvia D M Santos
Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis...
October 20, 2016: Molecular Cell
Jasmine S Berg, Dolma Michellod, Petra Pjevac, Clara Martinez-Perez, Caroline R T Buckner, Philipp F Hach, Carsten J Schubert, Jana Milucka, Marcel M M Kuypers
Iron redox reactions play an important role in carbon remineralization, supporting large microbial communities in iron-rich terrestrial and aquatic sediments. Stratified water columns with comparably low iron concentrations are globally widespread, but microbial iron cycling in these systems has largely been ignored. We found evidence for unexpectedly high iron turnover rates in the low (1-2 µmol·l(-1) ) iron waters of Lake Cadagno. Light-dependent, biological iron oxidation rates (1.4-13.8 µmol·l(-1) ·d(-1) ) were even higher than in ferruginous lakes with well-studied microbial iron cycles...
October 21, 2016: Environmental Microbiology
Olivier Taboureau, Karine Audouze
During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information and their disease relationships from the reported TDDB database...
October 21, 2016: ALTEX
Nitzan Krinsky, Maya Kaduri, Janna Shainsky-Roitman, Mor Goldfeder, Eran Ivanir, Itai Benhar, Yuval Shoham, Avi Schroeder
Cell-free protein synthesis (CFPS) systems are important laboratory tools that are used for various synthetic biology applications. Here, we present a simple and inexpensive laboratory-scale method for preparing a CFPS system from E. coli. The procedure uses basic lab equipment, a minimal set of reagents, and requires less than one hour to process the bacterial cell mass into a functional S30-T7 extract. BL21(DE3) and MRE600 E. coli strains were used to prepare the S30-T7 extract. The CFPS system was used to produce a set of fluorescent and therapeutic proteins of different molecular weights (up to 66 kDa)...
2016: PloS One
Liangliang Chen, Yuancheng Peng, Juan Tian, Xiaohong Wang, Zhaosheng Kong, Tonglin Mao, Ming Yuan, Yunhai Li
How cell shape is controlled is a fundamental question in developmental biology, but the genetic and molecular mechanisms that determine cell shape are largely unknown. Arabidopsis trichomes have been used as a good model system to investigate cell shape at the single-cell level. Here we describe the trichome cell shape 1 (tcs1) mutants with the reduced trichome branch number in Arabidopsis. TCS1 encodes a coiled-coil domain-containing protein. Pharmacological analyses and observations of microtubule dynamics show that TCS1 influences the stability of microtubules...
October 2016: PLoS Genetics
Ruben Perez-Carrasco, Pilar Guerrero, James Briscoe, Karen M Page
During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms...
October 2016: PLoS Computational Biology
Robert J Gillespie, Derrick M Knapik, Ozan Akkus
Rotator cuff injuries are common in both young and elderly patients. Despite improvements in instrumentation and surgical techniques, the failure rates following tendon reconstruction remain unacceptably high. To improve outcomes, graft patches have been developed to provide mechanical strength and to furnish a scaffold for biologic growth across the delicate tendon-bone junction. Although no patch effectively re-creates the structured, highly organized system of prenatal tendon development, augmenting rotator cuff repair may help restore native tendon-to-bone attachment while reproducing the mechanical and biologic properties of native tendon...
October 20, 2016: Journal of the American Academy of Orthopaedic Surgeons
Allegra T Aron, Morten O Loehr, Jana Bogena, Christopher J Chang
Iron is essential for sustaining life, as its ability to cycle between multiple oxidation states is critical for catalyzing chemical transformations in biological systems. However, without proper regulation, this same redox capacity can trigger oxidative stress events that contribute to aging along with diseases ranging from cancer to cardiovascular and neurodegenerative disorders. Despite its importance, methods for monitoring biological iron bound weakly to cellular ligands-the labile iron pool-to generate a response that preserves spatial and temporal information remain limited, owing to the potent fluorescence quenching ability of iron...
October 21, 2016: Journal of the American Chemical Society
Jesús Ignacio Mendieta-Moreno, Daniel G Trabada, Jesus Mendieta, James P Lewis, Paulino Gómez-Puertas, Jose Ortega
The absorption of ultraviolet radiation by DNA may result in harmful genetic lesions that affect DNA replication and transcription, ultimately causing mutations, cancer and/or cell death. We analyze the most abundant photochemical reaction in DNA, the cyclobutane thymine dimer, using hybrid quantum mechanics / molecular mechanics (QM/MM) techniques and QM/MM nonadiabatic molecular dynamics. We find that, due to its double helix structure, DNA presents a free energy barrier between non-reactive and reactive conformations leading to the photolesion...
October 21, 2016: Journal of Physical Chemistry Letters
Stephanie Heinzlmeir, Denis Kudlinzki, Sridhar Sreeramulu, Susan Klaeger, Santosh Lakshmi Gande, Verena Linhard, Mathias Wilhelm, Huichao Qiao, Dominic Helm, Benjamin Ruprecht, Krishna Saxena, Guillaume Médard, Harald Schwalbe, Bernhard Kuster
The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis and treatment resistance yet therapeutic targeting, drug discovery or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical proteomics to survey 235 clinical kinase inhibitors for their kinase selectivity and identified 24 drugs with sub-micromolar affinities for EPHA2. NMR-based conformational dynamics together with nine new co-crystal structures delineated drug-EPHA2 interactions in full detail...
October 21, 2016: ACS Chemical Biology
R D Astumian
Molecular machines use external energy to drive transport, to do mechanical, osmotic, or electrical work on the environment, and to form structure. In this paper the fundamental difference between the design principles necessary for a molecular machine to use light or external modulation of thermodynamic parameters as an energy source vs. the design principle for using an exergonic chemical reaction as a fuel will be explored. The key difference is that for catalytically-driven motors microscopic reversibility must hold arbitrarily far from equilibrium...
October 21, 2016: Faraday Discussions
Alexander N Zelikin, Carsten Ehrhardt, Anne Marie Healy
Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs...
October 21, 2016: Nature Chemistry
Kristin Bösch, Lamprinos Frantzeskakis, Miroslav Vraneš, Jörg Kämper, Kerstin Schipper, Vera Göhre
Gene deletion plays an important role in the analysis of gene function. One of the most efficient methods to disrupt genes in a targeted manner is the replacement of the entire gene with a selectable marker via homologous recombination. During homologous recombination, exchange of DNA takes place between sequences with high similarity. Therefore, linear genomic sequences flanking a target gene can be used to specifically direct a selectable marker to the desired integration site. Blunt ends of the deletion construct activate the cell's DNA repair systems and thereby promote integration of the construct either via homologous recombination or by non-homologous-end-joining...
September 30, 2016: Journal of Visualized Experiments: JoVE
Antanas Spokevicius, Lynette Taylor, Emma Melder, Kim Van Beveren, Josquin Tibbits, Nicky Creux, Gerd Bossinger
Secondary stem growth in trees and associated wood formation are significant both from biological and commercial perspectives. However, relatively little is known about the molecular control that governs their development. This is in part due to physical, resource and time limitations often associated with the study of secondary growth processes. A number of in vitro techniques have been used involving either plant part or whole plant system in both woody and non-woody plant species. However, questions about their applicability for the study of secondary stem growth processes, the recalcitrance of certain species and labor intensity are often prohibitive for medium to high throughput applications...
October 5, 2016: Journal of Visualized Experiments: JoVE
Ellen L Mintz, Juliana A Passipieri, Daniel Y Lovell, George J Christ
Despite the regenerative capacity of skeletal muscle, permanent functional and/or cosmetic deficits (e.g., volumetric muscle loss (VML) resulting from traumatic injury, disease and various congenital, genetic and acquired conditions are quite common. Tissue engineering and regenerative medicine technologies have enormous potential to provide a therapeutic solution. However, utilization of biologically relevant animal models in combination with longitudinal assessments of pertinent functional measures are critical to the development of improved regenerative therapeutics for treatment of VML-like injuries...
October 7, 2016: Journal of Visualized Experiments: JoVE
Natália Helen Ferreira, Kelly Jacqueline Barbosa de Andrade, Luís Fernando Leandro, Nathália Oliveira Acésio, Suzana Amorim Mendes, Lucas Silva Cintra, Ana Helena Januário, Denise Crispim Tavares
The aim of this study was to examine the cytotoxic and genotoxic potential of a hydroethanolic extract of Schefflera vinosa (SV), a plant with schistosomicidal activity, as well as its influence on DNA damage induced by different mutagens, methyl methane sulfonate (MMS) and hydrogen peroxide (H2O2), in V79 cells and Swiss mice. Schefflera vinosa extract produced cytotoxicity at concentrations of 312.5 µg/ml or higher using the XTT cell proliferation assay kit. Treatment of V79 cell cultures with the highest SV concentration tested (150 µg/ml) significantly increased the frequency of micronuclei (MN) compared to controls...
October 21, 2016: Journal of Toxicology and Environmental Health. Part A
Ali Kermanizadeh, Klaus Villadsen, Ragnhild G Østrem, Knud J Jensen, Peter Møller, Steffen Loft
Utilisation of functionalized liposomes as the means of targeted delivery of therapeutics may enhance specific transport of biologically active drugs to target tissues, while avoiding or reducing undesired side effects. In the present investigation, peptide-conjugated cationic liposomes were constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells and macrophages...
October 21, 2016: Basic & Clinical Pharmacology & Toxicology
Ludovic Enkler, Delphine Richer, Anthony L Marchand, Dominique Ferrandon, Fabrice Jossinet
Among Candida species, the opportunistic fungal pathogen Candida glabrata has become the second most common causative agent of candidiasis in the world and a major public health concern. Yet, few molecular tools and resources are available to explore the biology of C. glabrata and to better understand its virulence during infection. In this study, we describe a robust experimental strategy to generate loss-of-function mutants in C. glabrata. The procedure is based on the development of three main tools: (i) a recombinant strain of C...
October 21, 2016: Scientific Reports
Jenny Y Y Lau, Chun-Chiu Pang, Lawrence Ramsden, Richard M K Saunders
The floral phenology, pollination ecology and breeding systems of two sympatric early-divergent angiosperms, Goniothalamus tapisoides and G. suaveolens (Annonaceae) are compared. The flowers are protogynous and morphologically similar, with anthesis over 23-25 h. Both species are predominantly xenogamous and pollinated by small beetles: G. tapisoides mainly by Curculionidae and G. suaveolens mainly by Nitidulidae. Coevolution and reproductive resource partitioning, reducing interspecific pollen transfer, is achieved by temporal isolation, due to contrasting floral phenologies; and ethological isolation, due to contrasting floral scents that contain attractants specific to the two beetle families...
October 21, 2016: Scientific Reports
Akihiro Orita, Michael G Verde, Masanori Sakai, Ying Shirley Meng
The versatility in design of redox flow batteries makes them apt to efficiently store energy in large-scale applications at low cost. The discovery of inexpensive organic electroactive materials for use in aqueous flow battery electrolytes is highly attractive, but is thus far limited. Here we report on a flow battery using an aqueous electrolyte based on the sodium salt of flavin mononucleotide. Flavins are highly versatile electroactive molecules, which catalyse a multitude of redox reactions in biological systems...
October 21, 2016: Nature Communications
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