scholarly journals Build-a-Cell: Engineering a Synthetic Cell Community

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1176
Author(s):  
Caroline Frischmon ◽  
Carlise Sorenson ◽  
Michael Winikoff ◽  
Katarzyna P. Adamala
Keyword(s):  
Large Scale ◽  
Global Network ◽  
Integration Step ◽  
Cellular Functions ◽  
Complete Understanding ◽  
Synthetic Cell ◽  
Synthetic Cells ◽  
A Cell ◽  
Scientists And Engineers ◽  
Cell Community

Build-a-Cell is a global network of researchers that aims to develop synthetic living cells within the next decade. These cells will revolutionize the biotechnology industry by providing scientists and engineers with a more complete understanding of biology. Researchers can already replicate many cellular functions individually, but combining them into a single cell remains a significant challenge. This integration step will require the type of large-scale collaboration made possible by Build-a-Cell’s open, collective structure. Beyond the lab, Build-a-Cell addresses policy issues and biosecurity concerns associated with synthetic cells. The following review discusses Build-a-Cell’s history, function, and goals.

Integration of Ecological and Engineering Aspects in Planning Large Scale Tidal Power Development in the Bay of Fundy, Canada

1984 ◽  
Vol 16 (1-2) ◽  
pp. 281-295 ◽  
Author(s):  
Donald C Gordon
Keyword(s):  
Large Scale ◽  
Feasibility Studies ◽  
Bay Of Fundy ◽  
Final Decision ◽  
Power Development ◽  
Tidal Power ◽  
History Of ◽  
Scientists And Engineers ◽  
The Many ◽  
University Scientists

Large-scale tidal power development in the Bay of Fundy has been given serious consideration for over 60 years. There has been a long history of productive interaction between environmental scientists and engineers durinn the many feasibility studies undertaken. Up until recently, tidal power proposals were dropped on economic grounds. However, large-scale development in the upper reaches of the Bay of Fundy now appears to be economically viable and a pre-commitment design program is highly likely in the near future. A large number of basic scientific research studies have been and are being conducted by government and university scientists. Likely environmental impacts have been examined by scientists and engineers together in a preliminary fashion on several occasions. A full environmental assessment will be conducted before a final decision is made and the results will definately influence the outcome.

scholarly journals Reconfiguration of human evolving large-scale epileptic brain networks prior to seizures: an evaluation with node centralities

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rieke Fruengel ◽  
Timo Bröhl ◽  
Thorsten Rings ◽  
Klaus Lehnertz
Keyword(s):  
Large Scale ◽  
Brain Networks ◽  
Brain Regions ◽  
Brain Network ◽  
Theoretical Concept ◽  
Global Network ◽  
Time Resolved ◽  
Functional Connections ◽  
Node Centrality ◽  
Network Mechanism

AbstractPrevious research has indicated that temporal changes of centrality of specific nodes in human evolving large-scale epileptic brain networks carry information predictive of impending seizures. Centrality is a fundamental network-theoretical concept that allows one to assess the role a node plays in a network. This concept allows for various interpretations, which is reflected in a number of centrality indices. Here we aim to achieve a more general understanding of local and global network reconfigurations during the pre-seizure period as indicated by changes of different node centrality indices. To this end, we investigate—in a time-resolved manner—evolving large-scale epileptic brain networks that we derived from multi-day, multi-electrode intracranial electroencephalograpic recordings from a large but inhomogeneous group of subjects with pharmacoresistant epilepsies with different anatomical origins. We estimate multiple centrality indices to assess the various roles the nodes play while the networks transit from the seizure-free to the pre-seizure period. Our findings allow us to formulate several major scenarios for the reconfiguration of an evolving epileptic brain network prior to seizures, which indicate that there is likely not a single network mechanism underlying seizure generation. Rather, local and global aspects of the pre-seizure network reconfiguration affect virtually all network constituents, from the various brain regions to the functional connections between them.

Sterol and lipid trafficking in mammalian cells

2006 ◽  
Vol 34 (3) ◽  
pp. 335-339 ◽  
Author(s):  
F.R. Maxfield ◽  
M. Mondal
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Intracellular Transport ◽  
Vesicular Transport ◽  
Cholesterol Content ◽  
Cellular Functions ◽  
Lipid Trafficking ◽  
Sterol Transport ◽  
A Cell ◽  
Asymmetrically Distributed

The pathways involved in the intracellular transport and distribution of lipids in general, and sterols in particular, are poorly understood. Cholesterol plays a major role in modulating membrane bilayer structure and important cellular functions, including signal transduction and membrane trafficking. Both the overall cholesterol content of a cell, as well as its distribution in specific organellar membranes are stringently regulated. Several diseases, many of which are incurable at present, have been characterized as results of impaired cholesterol transport and/or storage in the cells. Despite their importance, many fundamental aspects of intracellular sterol transport and distribution are not well understood. For instance, the relative roles of vesicular and non-vesicular transport of cholesterol have not yet been fully determined, nor are the non-vesicular transport mechanisms well characterized. Similarly, whether cholesterol is asymmetrically distributed between the two leaflets of biological membranes, and if so, how this asymmetry is maintained, is poorly understood. In this review, we present a summary of the current understanding of these aspects of intracellular trafficking and distribution of lipids, and more specifically, of sterols.

Disaster impacts in a port-city; learning from Beirut's  Port explosion

2021 ◽  
Author(s):  
Steluta topalov
Keyword(s):  
Large Scale ◽  
Focal Point ◽  
Transportation System ◽  
The Philippines ◽  
Lessons Learned ◽  
Social Dimension ◽  
Global Network ◽  
Port Cities ◽  
Residential Units ◽  
The Impact

<p>On 4 august 2020, one of the biggest non-nuclear explosions the world has seen in recent times took place in the Port of Beirut. Caused by the detonation of 2,750 tons of ammonium nitrate, inadequate stored in a warehouse in the port, the blast destroyed much of the city’s port and the surrounding infrastructure and severly  damaged the dense residential and commercial areas within 5 km of the explosion site. The impact of the explosion, which registered as a 3.3 magnitude earthquake according to the U.S. Geological Survey, was felt as far away as the island of Cyprus.</p><p>Athough the event was an technological hazard, the impact of the explosion is similar to a standardised natural disaster.</p><p>According to UNDP, a total of 200 000 residential units were affected with an estimated of 40 000 buildings damaged; 200 people lost their lives, around 6 000 individuals were injuried and around 300 000 people were displaced.</p><p>Such figure are comparable to other large-scale disasters such as Cyclone Vayu in India, which occured in June 2019 or the displacement caused by the Typhoon Vongfong, in the Philippines.</p><p>The frequent increase of the natural disasters  puts pressure on the critical infrastructure of the cities. The disruption of the transportation system,  which is vital for the sustainable daily operations, are having a big impact on the economical, enviromental and social dimension of a city system. Among the various types of transportation system, ports are a focal point because of its strategic role for the economic growth of cities,regions and  global network. In addition, they are nodal points for the social and economical activity of the inhabitants.</p><p>Although the ports have played a key role in the development of their host cities, they are also vulnerable to a broad range of risks and threats because of a particular spatial character: the location at the intersection of land and sea.  </p><p>The study of the Beirut’s Port explosion examines the impact of port failures on the host urban enviroment and the relationship between hazards, vulnerability and the impact. The vulnerability of the port to disasters results  to the vulnerability of its host city. A context –based understanding  of the impact of the disaster and the elements at risk is essential to identify appropriate risk management strategies. The location of the port within the urban environment, in densely populated area, as in case of Beirut are some of the characteristics of the port cities that can magnify the impact of disasters to which they are prone.  The study will focus on a collection of data that records the impact and allows visualisation of the complex patterns of the disaster risk reduction.</p><p>The impact caused by the Beirut’s port explosion reminds us about the important role of the ports in their host cities and how fundamental is to identify the port’s infrastructure  exposure to hazards and risks.  Lessons learned from such event may be useful to reduce disaster risks in the port cities.</p>

scholarly journals Proteomic Signatures of Clostridium difficile Stressed with Metronidazole, Vancomycin, or Fidaxomicin

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 213 ◽  
Author(s):  
Sandra Maaß ◽  
Andreas Otto ◽  
Dirk Albrecht ◽  
Katharina Riedel ◽  
Anke Trautwein-Schult ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Antibiotic Treatment ◽  
Antimicrobial Agents ◽  
Cell Envelope ◽  
Protein Biosynthesis ◽  
Cellular Functions ◽  
Antibiotic Resistant ◽  
Incidence And Mortality ◽  
A Cell ◽  
Proteomic Response

The anaerobic pathogen Clostridium difficile is of growing significance for the health care system due to its increasing incidence and mortality. As C. difficile infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen’s responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of C. difficile 630∆erm to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of C. difficile allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms.

scholarly journals Permeabilization of rat hepatocytes with Staphylococcus aureus alpha-toxin.

1985 ◽  
Vol 100 (6) ◽  
pp. 1922-1929 ◽  
Author(s):  
B F McEwen ◽  
W J Arion
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Rat Hepatocytes ◽  
Alpha Toxin ◽  
Cellular Functions ◽  
Transmembrane Channel ◽  
Selective Permeability ◽  
Treatment Conditions ◽  
Transmission Electron ◽  
A Cell

Pathogenic staphylococci secrete a number of exotoxins, including alpha-toxin. alpha-Toxin induces lysis of erythrocytes and liposomes when its 3S protein monomers associate with the lipid bilayer and form a hexomeric transmembrane channel 3 nm in diameter. We have used alpha-toxin to render rat hepatocytes 93-100% permeable to trypan blue with a lactate dehydrogenase leakage less than or equal to 22%. Treatment conditions included incubation for 5-10 min at 37 degrees C and pH 7.0 with an alpha-toxin concentration of 4-35 human hemolytic U/ml and a cell concentration of 13-21 mg dry wt/ml. Scanning electron microscopy revealed signs of swelling in the treated hepatocytes, but there were no large lesions or gross damage to the cell surface. Transmission electron microscopy indicated that the nucleus, mitochondria, and cytoplasm were similar in control and treated cells and both had large regions of well-defined lamellar rough endoplasmic reticulum. Comparisons of the mannose-6-phosphatase and glucose-6-phosphatase activities demonstrated that 5-10 U/ml alpha-toxin rendered cells freely permeable to glucose-6-phosphate, while substantially preserving the selective permeability of the membranes of the endoplasmic reticulum and the functionality of the glucose-6-phosphatase system. Thus, alpha-toxin appears to have significant potential as a means to induce selective permeability to small ions. It should make possible the study of a variety of cellular functions in situ.

scholarly journals Elucidating the molecular determinants of Aβ aggregation with deep mutational scanning

2019 ◽  
Author(s):  
Vanessa E. Gray ◽  
Katherine Sitko ◽  
Floriane Z. Ngako Kameni ◽  
Miriam Williamson ◽  
Jason J. Stephany ◽  
...  
Keyword(s):  
Large Scale ◽  
Single Amino Acid ◽  
Alanine Scanning Mutagenesis ◽  
Aggregation Assay ◽  
Disease Etiology ◽  
Charged Amino Acids ◽  
Molecular Determinants ◽  
Aβ Aggregation ◽  
A Cell

AbstractDespite the importance of Aβ aggregation in Alzheimer’s disease etiology, our understanding of the sequence determinants of aggregation is sparse and largely derived from in vitro studies. For example, in vitro proline and alanine scanning mutagenesis of Aβ40 proposed core regions important for aggregation. However, we lack even this limited mutagenesis data for the more disease-relevant Aβ42. Thus, to better understand the molecular determinants of Aβ42 aggregation in a cell-based system, we combined a yeast DHFR aggregation assay with deep mutational scanning. We measured the effect of 791 of the 798 possible single amino acid substitutions on the aggregation propensity of Aβ42. We found that ~75% of substitutions, largely to hydrophobic residues, maintained or increased aggregation. We identified 11 positions at which substitutions, particularly to hydrophilic and charged amino acids, disrupted Aβ aggregation. These critical positions were similar but not identical to critical positions identified in previous Aβ mutagenesis studies. Finally, we analyzed our large-scale mutagenesis data in the context of different Aβ aggregate structural models, finding that the mutagenesis data agreed best with models derived from fibrils seeded using brain-derived Aβ aggregates.

scholarly journals Governing the School by Transnational Networks. The OECD PISA Policy Advisor Network in the Global Field of Power.

2020 ◽  
Author(s):  
Oliver Wieczorek ◽  
Richard Münch ◽  
Alexander Brand ◽  
Silvia Schwanhäuser
Keyword(s):  
Global Education ◽  
Large Scale ◽  
Global Field ◽  
Global Network ◽  
Educational Reforms ◽  
Collaboration Network ◽  
Scientific Cooperation ◽  
Key Players ◽  
Different Types ◽  
Governance Reforms

The OECD is one of the key players in global education policy advice, informing education governance reforms around the globe with the PISA test. At the same time, it is part of the edu-business network comprised of companies, philanthropies, consulting agencies and think tanks profiting from educational governance reforms and large-scale testing. In order to exert influence on national educational reforms, different types of complementary expertise and collaborations between different types of actors must be coordinated. To analyze this form of collaboration between different actors and to map the global edu-business and global policy advisor networks having emerged around the OECD’s PISA-tests, we make use of a combination of Habitus-Field Theory and Social Network Theory. We introduce the concepts of boundary-spanning actors and field-transcending social capital and apply our concepts to a two-level network analysis to investigate the embeddedness of the OECD in different social fields and the global field of power. The first layer is based on official collaborations among organizational actors situated in different sectors of the field of power. The second layer comprises of individual collaborations such as scientific cooperation, board interlocks and multiple affiliations. Furthermore, we look at network closure and density to investigate the exclusion of competing actors from taking part in the global edu-business. Our findings indicate that the OECD draws on experts and actors located in different fields to exert influence on national educational reforms. Finally, the global network of policy advisors is able to coordinate the different forms of expertise by installing a system of patronage, consisting of a small number of key players and large numbers of organizations and individuals that are needed to set education reforms in motion but are excluded from the core of the collaboration network.

scholarly journals CrosstalkNet: mining large-scale bipartite co-expression networks to characterize epi-stroma crosstalk

2017 ◽  
Author(s):  
Venkata Manem ◽  
George Adam ◽  
Tina Gruosso ◽  
Mathieu Gigoux ◽  
Nicholas Bertos ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Large Scale ◽  
Network Visualization ◽  
Visualization Tool ◽  
Biological Processes ◽  
Web Based ◽  
Link Type ◽  
A Cell ◽  
Large Scale Networks ◽  
User Friendly

ABSTRACTBackground:Over the last several years, we have witnessed the metamorphosis of network biology from being a mere representation of molecular interactions to models enabling inference of complex biological processes. Networks provide promising tools to elucidate intercellular interactions that contribute to the functioning of key biological pathways in a cell. However, the exploration of these large-scale networks remains a challenge due to their high-dimensionality.Results:CrosstalkNet is a user friendly, web-based network visualization tool to retrieve and mine interactions in large-scale bipartite co-expression networks. In this study, we discuss the use of gene co-expression networks to explore the rewiring of interactions between tumor epithelial and stromal cells. We show how CrosstalkNet can be used to efficiently visualize, mine, and interpret large co-expression networks representing the crosstalk occurring between the tumour and its microenvironment.Conclusion:CrosstalkNet serves as a tool to assist biologists and clinicians in exploring complex, large interaction graphs to obtain insights into the biological processes that govern the tumor epithelial-stromal crosstalk. A comprehensive tutorial along with case studies are provided with the application.Availability:The web-based application is available at the following location: http://epistroma.pmgenomics.ca/app/. The code is open-source and freely available from http://github.com/bhklab/EpiStroma-webapp.Contact:[email protected]

scholarly journals Mechanics defines the spatial pattern of compensatory proliferation

2021 ◽  
Author(s):  
Takumi Kawaue ◽  
Ivan Yow ◽  
Anh Phuong Le ◽  
Yuting Lou ◽  
Mavis Loberas ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Cell Loss ◽  
Spatial Inhomogeneity ◽  
Cellular Functions ◽  
Cell Numbers ◽  
Compensatory Proliferation ◽  
A Cell ◽  
Growth Promoting ◽  
Open Question

The number of cells in tissues is tightly controlled by cell division and cell death, and misregulation of cell numbers could lead to pathological conditions such as cancer. To maintain cell numbers in a tissue, a cell elimination process named programmed cell death or apoptosis, stimulates the proliferation of neighboring cells. This mechanism is called apoptosis-induced compensatory proliferation, which was originally reported more than 40 years ago. While only a limited number of the neigboring cells need to divide to compensate for apoptotic cell loss, the mechanisms that select cells for undergoing division remain an open question. Here we found that the spatial inhomogeneity in mechanotransduction through a growth-promoting transcription co-activator Yes-associated protein (YAP) in the neighboring tissue, accounts for the inhomogeneity of compensatory proliferation. Such inhomogeneous mechanotransduction arises from the combination of the non-uniform distribution of nuclear size, which is inherent in tissues, and the non-uniform pattern of mechanical force applied to the neighboring cells upon apoptosis. Our findings from a mechanical perspective complement the current biochemical understanding of compensatory growth and provide additional insights into cellular functions of how tissue precisely maintains its homeostasis.

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