Fluorescence microscopy tensor imaging representations for large-scale dataset analysis.

Sci Rep. 2020 Mar 27;10(1):5632

Authors: Vinegoni C, Fumene Feruglio P, Courties G, Schmidt S, Hulsmans M, Lee S, Wang R, Sosnovik D, Nahrendorf M, Weissleder R

Abstract
Understanding complex biological systems requires the system-wide characterization of cellular and molecular features. Recent advances in optical imaging technologies and chemical tissue clearing have facilitated the acquisition of whole-organ imaging datasets, but automated tools for their quantitative analysis and visualization are still lacking. We have here developed a visualization technique capable of providing whole-organ tensor imaging representations of local regional descriptors based on fluorescence data acquisition. This method enables rapid, multiscale, analysis and virtualization of large-volume, high-resolution complex biological data while generating 3D tractographic representations. Using the murine heart as a model, our method allowed us to analyze and interrogate the cardiac microvasculature and the tissue resident macrophage distribution and better infer and delineate the underlying structural network in unprecedented detail.

PMID: 32221334 [PubMed - as supplied by publisher]

Genome-scale metabolic models of Microbacterium species isolated from a high altitude desert environment.

Sci Rep. 2020 Mar 27;10(1):5560

Authors: Mandakovic D, Cintolesi Á, Maldonado J, Mendoza SN, Aïte M, Gaete A, Saitua F, Allende M, Cambiazo V, Siegel A, Maass A, González M, Latorre M

Abstract
The Atacama Desert is the most arid desert on Earth, focus of important research activities related to microbial biodiversity studies. In this context, metabolic characterization of arid soil bacteria is crucial to understand their survival strategies under extreme environmental stress. We investigated whether strain-specific features of two Microbacterium species were involved in the metabolic ability to tolerate/adapt to local variations within an extreme desert environment. Using an integrative systems biology approach we have carried out construction and comparison of genome-scale metabolic models (GEMs) of two Microbacterium sp., CGR1 and CGR2, previously isolated from physicochemically contrasting soil sites in the Atacama Desert. Despite CGR1 and CGR2 belong to different phylogenetic clades, metabolic pathways and attributes are highly conserved in both strains. However, comparison of the GEMs showed significant differences in the connectivity of specific metabolites related to pH tolerance and CO2 production. The latter is most likely required to handle acidic stress through decarboxylation reactions. We observed greater GEM connectivity within Microbacterium sp. CGR1 compared to CGR2, which is correlated with the capacity of CGR1 to tolerate a wider pH tolerance range. Both metabolic models predict the synthesis of pigment metabolites (β-carotene), observation validated by HPLC experiments. Our study provides a valuable resource to further investigate global metabolic adaptations of bacterial species to grow in soils with different abiotic factors within an extreme environment.

PMID: 32221328 [PubMed - as supplied by publisher]

Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV.

Nat Commun. 2020 Mar 27;11(1):1620

Authors: Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, Chen J, Hu K, Jin Q, Wang J, Qian Z

Abstract
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

PMID: 32221306 [PubMed - as supplied by publisher]

Accumulation of high-value bioproducts in planta can improve the economics of advanced biofuels.

Proc Natl Acad Sci U S A. 2020 Mar 27;:

Authors: Yang M, Baral NR, Simmons BA, Mortimer JC, Shih PM, Scown CD

Abstract
Coproduction of high-value bioproducts at biorefineries is a key factor in making biofuels more cost-competitive. One strategy for generating coproducts is to directly engineer bioenergy crops to accumulate bioproducts in planta that can be fractionated and recovered at biorefineries. Here, we develop quantitative insights into the relationship between bioproduct market value and target accumulation rates by investigating a set of industrially relevant compounds already extracted from plant sources with a wide range of market prices and applications, including <$10/kg (limonene, latex, and polyhydroxybutyrate [PHB]), $10 to $100/kg (cannabidiol), and >$100/kg (artemisinin). These compounds are used to identify a range of mass fraction thresholds required to achieve net economic benefits for biorefineries and the additional amounts needed to reach a target $2.50/gal biofuel selling price, using cellulosic ethanol production as a test case. Bioproduct market prices and recovery costs determine the accumulation threshold; we find that moderate- to high-value compounds (i.e., cannabidiol and artemisinin) offer net economic benefits at accumulation rates of just 0.01% dry weight (dwt) to 0.02 dwt%. Lower-value compounds, including limonene, latex, and PHB, require at least an order-of-magnitude greater accumulation to overcome additional extraction and recovery costs (0.3 to 1.2 dwt%). We also find that a diversified approach is critical. For example, global artemisinin demand could be met with fewer than 10 biorefineries, while global demand for latex is equivalent to nearly 180 facilities. Our results provide a roadmap for future plant metabolic engineering efforts aimed at increasing the value derived from bioenergy crops.

PMID: 32220956 [PubMed - as supplied by publisher]

The Loss of TBK1 Kinase Activity in Motor Neurons or in All Cell Types Differentially Impacts ALS Disease Progression in SOD1 Mice.

Neuron. 2020 Mar 23;:

Authors: Gerbino V, Kaunga E, Ye J, Canzio D, O'Keeffe S, Rudnick ND, Guarnieri P, Lutz CM, Maniatis T

Abstract
DNA sequence variants in the TBK1 gene associate with or cause sporadic or familial amyotrophic lateral sclerosis (ALS). Here we show that mice bearing human ALS-associated TBK1 missense loss-of-function mutations, or mice in which the Tbk1 gene is selectively deleted in motor neurons, do not display a neurodegenerative disease phenotype. However, loss of TBK1 function in motor neurons of the SOD1G93A mouse model of ALS impairs autophagy, increases SOD1 aggregation, and accelerates early disease onset without affecting lifespan. By contrast, point mutations that decrease TBK1 kinase activity in all cells also accelerate disease onset but extend the lifespan of SOD1 mice. This difference correlates with the failure to activate high levels of expression of interferon-inducible genes in glia. We conclude that loss of TBK1 kinase activity impacts ALS disease progression through distinct pathways in different spinal cord cell types and further implicate the importance of glia in neurodegeneration.

PMID: 32220666 [PubMed - as supplied by publisher]

The shell matrix of the European thorny oyster, Spondylus gaederopus: microstructural and molecular characterization.

J Struct Biol. 2020 Mar 24;:107497

Authors: Sakalauskaite J, Plasseraud L, Thomas J, Albéric M, Thoury M, Perrin J, Jamme F, Broussard C, Demarchi B, Marin F

Abstract
Molluscs, the largest marine phylum, display extraordinary shell diversity and sophisticated biomineral architectures. However, mineral-associated biomolecules involved in biomineralization are still poorly characterized. We report the first comprehensive structural and biomolecular study of Spondylus gaederopus, a pectinoid bivalve with a peculiar shell texture. Used since prehistoric times, this is the best-known shell of Europe's cultural heritage. We find that Spondylus microstructure is very poor in mineral-bound organics, which are mostly intercrystalline and concentrated at the interface between structural layers. Using high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) we characterized several shell protein fractions, isolated following different bleaching treatments. Several peptides were identified as well as six shell proteins, which display features and domains typically found in biomineralized tissues, including the prevalence of intrinsically disordered regions. It is very likely that these sequences only partially represent the full proteome of Spondylus, considering the lack of genomics data for this genus and the fact that most of the reconstructed peptides do not match with any known shell proteins, representing consequently lineage-specific sequences. This work sheds light onto the shell matrix involved in the biomineralization in spondylids. Our proteomics data suggest that Spondylus has evolved a shell-forming toolkit, distinct from that of other better studied pectinoids - fine-tuned to produce shell structures with high mechanical properties, while limited in organic content. This study therefore represents an important milestone for future studies on biomineralized skeletons and provides the first reference dataset for forthcoming molecular studies of Spondylus archaeological artifacts.

PMID: 32220629 [PubMed - as supplied by publisher]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

68 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The role of cooperativity in a p53-miR34 dynamical mathematical model.

J Theor Biol. 2020 Mar 18;:110252

Authors: Nikolov S, Wolkenhauer O, Vera J, Nenov M

Abstract
The objective of this study is to evaluate the role of cooperativity, captured by the Hill coefficient, in a minimal mathematical model describing the interactions between p53 and miR-34a. The model equations are analyzed for negative, none and normal cooperativity using a specific version of bifurcation theory and they are solved numerically. Special attention is paid to the sign of so-called first Lyapunov value. Interpretations of the results are given, both according to dynamic theory and in biological terms. In terms of cell signaling, we propose the hypothesis that when the outgoing signal of a system spends a physiologically significant amount of time outside of its equilibrium state, then the value of that signal can be sampled at any point along the trajectory towards that equilibrium and indeed, at multiple points. Coupled with non-linear behavior, such as that caused by cooperativity, this feature can account for a complex and varied response, which p53 is known for. From dynamical point of view, we found that when cooperativity is negative, the system has only one stable equilibrium point. In the absence of cooperativity, there is a single unstable equilibrium point with a critical boundary of stability. In the case with normal cooperativity, the system can have one, two, or three steady states with both, bi-stability and bi-instability occurring.

PMID: 32199858 [PubMed - as supplied by publisher]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/03/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.