Supramolecular polymers are composed of monomers that self-assemble non-covalently, generating distributions of monodimensional fibres in continuous communication with each other and with the ...surrounding solution. Fibres, exchanging molecular species, and external environment constitute a sole complex system, which intrinsic dynamics is hard to elucidate. Here we report coarse-grained molecular simulations that allow studying supramolecular polymers at the thermodynamic equilibrium, explicitly showing the complex nature of these systems, which are composed of exquisitely dynamic molecular entities. Detailed studies of molecular exchange provide insights into key factors controlling how assemblies communicate with each other, defining the equilibrium dynamics of the system. Using minimalistic and finer chemically relevant molecular models, we observe that a rich concerted complexity is intrinsic in such self-assembling systems. This offers a new dynamic and probabilistic (rather than structural) picture of supramolecular polymer systems, where the travelling molecular species continuously shape the assemblies that statistically emerge at the equilibrium.
Supramolecular fibers composed of monomers that self-assemble directionally via noncovalent interactions are ubiquitous in nature, and of great interest in chemistry. In these structures, the ...constitutive monomers continuously exchange in-and-out the assembly according to a well-defined supramolecular equilibrium. However, unraveling the exchange pathways and their molecular determinants constitutes a nontrivial challenge. Here, we combine coarse-grained modeling, enhanced sampling, and machine learning to investigate the key factors controlling the monomer exchange pathways in synthetic supramolecular polymers having an intrinsic dynamic behavior. We demonstrate how the competition of directional vs. nondirectional interactions between the monomers controls the creation/annihilation of defects in the supramolecular polymers, from where monomers exchange proceeds. This competition determines the exchange pathway, dictating whether a fiber statistically swaps monomers from the tips or from all along its length. Finally, thanks to their generality, our models allow the investigation of molecular approaches to control the exchange pathways in these dynamic assemblies.
Aims
Data on the decomposition of fine roots are scarce for the Mediterranean basin. This work aims to compare chemical traits, decomposition rate, and temperature sensitivity (
Q
10) for root and ...leaf litter of 43 Mediterranean species.
Methods
We carried out a two-years litterbag decomposition experiment using 43 fine roots litter and leaf litter types incubated in laboratory conditions at three different temperatures, i.e. 4 °C, 14 °C, and 24 °C. Litter was characterized for carbon (C), nitrogen (N), lignin and cellulose concentration, C/N, and lignin/N ratios.
Results
Fine root litter had lower N content but higher lignin concentration, lignin/N, and C/N ratios compared to leaf litter. The decay rate of fine root litter was slower than leaf litter. For both tissues, the decay rate was negatively associated with lignin concentration, lignin/N, and C/N ratios but positively with N concentration.
Q
10 was higher for fine root than leaf litter, with a positive correlation with lignin while negative with N concentration.
Conclusions
Our findings demonstrate a higher
Q
10 accompanied by a slower decomposition rate of fine root litter compared to leaf litter in Mediterranean ecosystems. These results must be considered in modeling organic C at the ecosystem scale.
Because plants are estimated to produce over 200,000 metabolites, research into new natural substances that can be used in the pharmaceutical, agrochemical and agro-industrial production of drugs, ...biopesticides and food additives has grown in recent years. The global market for plant-derived drugs over the last decade has been estimated to be approximately 30.69 billion USD. A relevant specific example of a plant that is very interesting for its numerous pharmacological properties, which include antidiabetic, anticarcinogenic, and neuroprotective effects is Gymnema sylvestre, used as a medicinal plant in Asia for thousands of years. Its properties are attributed to triterpenoidic saponins. In light of the considerable interest generated in the chemistry and pharmacological properties of G. sylvestre triterpenes and their analogues, we have undertaken this review in an effort to summarise the available literature on these promising bioactive natural products. The review will detail studies on the isolation, chemistry and bioactivity of the triterpenoids, which are presented in the tables. In particular the triterpenoids oxidised at C-23; their isolation, distribution in different parts of the plant, and their NMR spectral data; their names and physico-chemical characterisation; and the biological properties associated with these compounds, with a focus on their potential chemotherapeutic applications.
The control of the aggregation of biomedical nanoparticles (NP) in physiological conditions is crucial as clustering may change completely the way they interact with the biological environment. Here ...we show that Au nanoparticles, functionalized by an anionic, amphiphilic shell, spontaneously aggregate in fluid zwitterionic lipid bilayers. We use molecular dynamics and enhanced sampling techniques to disentangle the short-range and long-range driving forces of aggregation. At short inter-particle distances, ion-mediated, charge-charge interactions (ion bridging) stabilize the formation of large NP aggregates, as confirmed by cryo-electron microscopy. Lipid depletion and membrane curvature are the main membrane deformations driving long-range NP-NP attraction. Ion bridging, lipid depletion, and membrane curvature stem from the configurational flexibility of the nanoparticle shell. Our simulations show, more in general, that the aggregation of same-charge membrane inclusions can be expected as a result of intrinsically nanoscale effects taking place at the NP-NP and NP-bilayer soft interfaces.
Same-charge, monolayer-protected Au NPs aggregate in lipid membranes due to ion-brigding and lipid depletion.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in ...more than 3.7 million infections and 260,000 deaths as of 6 May 2020
. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about ...neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.
Display omitted
•NTD-targeting antibodies are a key part of immunity to SARS-CoV-2•NTD neutralizing antibodies target a single antigenic site of vulnerability•Neutralizing NTD antibodies protect hamsters from SARS-CoV-2 challenge•Variants of concern have mutations in the NTD that escape neutralization
McCallum et al. identify a supersite in the N-terminal domain of SARS-CoV-2 spike protein that is targeted by neutralizing antibodies and exhibits mutation in response to selective pressure.
A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal ...domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or from convalescent individuals exhibited neutralizing titers that were reduced 2- to 3.5-fold against the B.1.427/B.1.429 variant relative to wild-type pseudoviruses. The L452R mutation reduced neutralizing activity in 14 of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 of 10 NTD-specific mAbs because the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and the formation of a new disulfide bond, as revealed by mass spectrometry and structural studies.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern that is causing a new wave of ...infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and Delta spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the Delta amino-terminal domain. The angiotensin-converting enzyme 2 binding affinities of the Kappa and Delta receptor binding domains are comparable to the Wuhan-Hu-1 isolate, whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity.
Question
Cushion‐forming vascular plants are adapted to alpine environments and act as ecosystem engineers by moderating microclimate and creating a fertility island under their canopy. Most of the ...available studies on cushion ecology have been devoted to plant facilitation, but none used a holistic approach that considers the response of co‐existing plant species with other key ecosystem players. Here, we quantified the biogenic effect and facilitation capacity of Astragalus siculus, a spiny nitrogen‐fixing cushion plant, and test the hypothesis that the facilitation effect would increase with elevation as stress gradient.
Location
Mount Etna, the highest active volcano in the Mediterranean Basin.
Methods
We combined chemical characterization of the soil with a description of the soil microbiota by high‐throughput sequencing of bacterial and eukaryotic rRNA gene markers carried out at three elevations, that is 1650, 1900 and 2210 m a.s.l. In addition, we analysed the microclimate outside and inside the Astragalus canopy to assess the linkages between above‐ and below‐ground ecosystem compartments and quantified the occurrence of co‐existing vascular plants.
Results
Astragalus cushions have strong biogenic effects on above‐ and below‐ground conditions by dramatically increasing soil organic carbon and total nitrogen stocks at 1900 and 2210 m elevation. Moreover, a buffering of soil temperature and moisture regimes was recorded, with lower temperatures in summer but higher in winter inside the cushions. Cushions harbour a specific bacterial and fungal microbiota compared to external bare soil. Stem density and cushion height increase significantly with altitude, as does the nurse effect of the cushion on the growth and survival of co‐existing vascular plants.
Conclusions
As a result of cushion biogenic environmental changes, the effect of Astragalus on some of the co‐existing species shifted from negative or null at 1650 m to facilitative along the elevation gradient. Furthermore, our data show a relationship between Astragalus morphological traits and soil biogenic changes related to soil chemistry and microbiota that affect plant interaction and coexistence.
The biogenic effect and facilitation capacity of Astragalus siculus (a spiny nitrogen‐fixing cushion plant) shifts from negative or null at 1650 m to facilitative along the elevation gradient of Mt Etna (southern Italy). Furthermore, our data show a relationship between Astragalus morphological traits and soil biogenic changes, related to soil chemistry and microbiota that affect plant interaction and coexistence.
PDF
