Chirality effects in molecular chainmail.

Motivated by the observation of positive Gaussian curvature in kinetoplast DNA networks, we consider the effect of linking chirality in square lattice molecular chainmail networks using Langevin dynamics simulations and constrained gradient optimization. Linking chirality here refers to ordering of over-under versus under-over linkages between a loop and its neighbors. We consider fully alternating linking, maximally non-alternating, and partially non-alternating linking chiralities.

Traveling fronts in vibrated polar disks: At the crossroad between polar ordering and jamming.

We investigate experimentally the collective motion of polar vibrated disks in an annular geometry, varying both the packing fraction and the amplitude of the angular noise. For low enough noise and large enough density, an overall collective motion takes place along the tangential direction. The spatial organization of the flow reveals the presence of polar bands of large density, as expected from the commonly accepted picture of the transition to collective motion in systems of aligning polar active particles.

Kinetically Controlled Polyelectrolyte Complex Assembly of microRNA-Peptide Nanoparticles toward Treating Mesothelioma.

Broad size distributions and poor long-term colloidal stability of microRNA-carrying nanoparticles, especially those formed by polyelectrolyte complexation, represent major hurdles in realizing their clinical translation. Herein, peptide design is used alongside optimized flash nanocomplexation (FNC) to produce uniform peptide-based miRNA particles of exceptional stability that display anticancer activity against mesothelioma in vitro and in vivo. Modulating the content and display of lysine-based charge from small intrinsically disordered peptides used to complex miRNA proves essential in achieving stable colloids.

, a plant growth stimulating bacterium, and its metabolites isolated from (dollarweed).

A bacterium growing on infected leaves of , commonly known as dollarweed, was isolated and identified as . An ethyl acetate extract of tryptic soy broth (TSB) liquid culture filtrate of the bacterium was subjected to silica gel chromatography to isolate bioactive molecules. Indole was isolated as the major compound that gave a distinct, foul odor to the extract, together with phenethyl alcohol, phenol, tryptophol, -acyl-homoserine lactone, 3-(methylthio)-1-propanol, cyclo(L-pro-L-tyr), and cyclo(dehydroAla-L-Leu).

The Design of a Participatory Peptide Nucleic Acid Duplex Crosslinker to Enhance the Stiffness of Self-Assembled Peptide Gels.

Herein, peptide nucleic acids (PNAs) are employed in the design of a participatory duplex PNA-peptide crosslinking agent. Biophysical and mechanical studies show that crosslinkers present during peptide assembly leading to hydrogelation participate in the formation of fibrils while simultaneously installing crosslinks into the higher-order network that constitutes the peptide gel. The addition of 2 mol % crosslinker into the assembling system results in a ~100 % increase in mechanical stiffness without affecting the rate of peptide assembly or the local morphology of fibrils within the gel network.

De Novo Design of a Versatile Peptide-Based Coating to Impart Targeted Functionality at the Surface of Native Polystyrene.

Peptide sequence periodicity is a simple design tool that can be used to generate functional peptide-based surface coatings. De novo-designed peptide N-PEG-VK16 is characterized by a hydrophobic periodicity of two that avidly binds to native polystyrene priming its surface for subsequent targeted functionalization via chemical ligation. The peptidic portion of N-PEG-VK16 is responsible for surface binding, converting polystyrene's hydrophobic surface into a wettable and electrostatically charged environment that facilitates cell attachment.

Supramolecular Filament Hydrogel as a Universal Immunomodulator Carrier for Immunotherapy Combinations.

A major challenge of cancer immunotherapy is to develop delivery strategies that can effectively and safely augment the immune system's antitumor response. Here, we report on the design and synthesis of a peptide-based supramolecular filament (SF) hydrogel as a universal carrier for localized delivery of three immunomodulating agents of distinct action mechanisms and different molecular weights, including an aPD1 antibody, an IL15 cytokine, and a STING agonist (CDA). We show that hydrogelation can be triggered to occur upon intratumoral injection of SF solutions containing each of aPD1, IL15, or CDA.

A Staphylococcal Glucosaminidase Drives Inflammatory Responses by Processing Peptidoglycan Chains to Physiological Lengths.

The peptidoglycan of Staphylococcus aureus is a critical cell envelope constituent and virulence factor that subverts host immune defenses and provides protection against environmental stressors. Peptidoglycan chains of the S. aureus cell wall are processed to characteristically short lengths by the glucosaminidase SagB.

Polymer-chain configurations in active and passive baths.

The configurations taken by polymers embedded in out-of-equilibrium baths may have broad implications in a variety of biological systems. As such, they have attracted considerable interest, particularly in simulation studies. Here we analyze the distribution of configurations taken by a passive flexible chain in a bath of hard, self-propelled, vibrated disks and systematically compare it to that of the same flexible chain in a bath of hard, thermal-like, vibrated disks.

Ant waves-Spontaneous activity waves in fire-ant columns.

Active matter, which includes crowds of organisms, is composed of constituents that independently consume and dissipate energy. Some active matter systems have been shown to sustain the propagation of various types of waves, resulting from the interplay between density and alignment. Here, we examine a type of solitary wave in dense two-dimensional columns of , fire ants, in which the local activity, density and alignment all play a key role.

Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention.

Coronaviruses have historically precipitated global pandemics of severe acute respiratory syndrome (SARS) into devastating public health crises. Despite the virus's rapid rate of mutation, all SARS coronavirus 2 (SARS-CoV-2) variants are known to gain entry into host cells primarily through complexation with angiotensin-converting enzyme 2 (ACE2). Although ACE2 has potential as a druggable decoy to block viral entry, its clinical use is complicated by its essential biological role as a carboxypeptidase and hindered by its structural and chemical instability.

Antiviral supramolecular polymeric hydrogels by self-assembly of tenofovir-bearing peptide amphiphiles.

The development of long-acting antiviral therapeutic delivery systems is crucial to improve the current treatment and prevention of HIV and chronic HBV. We report here on the conjugation of tenofovir (TFV), an FDA approved nucleotide reverse transcriptase inhibitor (NRTI), to rationally designed peptide amphiphiles (PAs), to construct antiviral prodrug hydrogelators (TFV-PAs). The resultant conjugates can self-assemble into one-dimensional nanostructures in aqueous environments and consequently undergo rapid gelation upon injection into 1× PBS solution to create a drug depot.

Social interactions lead to motility-induced phase separation in fire ants.

Collections of fire ants are a form of active matter, as the ants use their internal metabolism to self-propel. In the absence of aligning interactions, theory and simulations predict that active matter with spatially dependent motility can undergo motility-induced phase separation. However, so far in experiments, the motility effects that drive this process have come from either crowding or an external parameter.

The Proteomic and Transcriptomic Landscapes Altered by Rgg2/3 Activity in Streptococcus pyogenes.

Streptococcus pyogenes, otherwise known as Group A Streptococcus (GAS), is an important and highly adaptable human pathogen with the ability to cause both superficial and severe diseases. Understanding how S. pyogenes senses and responds to its environment will likely aid in determining how it causes a breadth of diseases.

Janssen effect in columns of fire ants.

We study fire-ant columns, an active version of passive granular columns, and find that, despite the inherent activity of the ants and their natural tendency to rearrange, the ants develop force-chain structures that help support the weight of the column. Hence, the apparent mass at the bottom of the column saturates with added mass in a Janssen-like fashion, reminiscent of what is seen in passive-grain columns in wide containers. Activity-induced rearrangements within the column, however, lead to changes in the force-chain structure that slightly reduce the supportive nature of the force-chains over time and to fluctuations in the pressure at the bottom of the column that scale like the law of large numbers.

Leveraging the therapeutic, biological, and self-assembling potential of peptides for the treatment of viral infections.

Peptides and peptide-based materials have an increasing role in the treatment of viral infections through their use as active pharmaceutical ingredients, targeting moieties, excipients, carriers, or structural components in drug delivery systems. The discovery of peptide-based therapeutic compounds, coupled with the development of new stabilization and formulation strategies, has led to a resurgence of antiviral peptide therapeutics over the past two decades. The ability of peptides to bind cell receptors and to facilitate membrane penetration and subsequent intracellular trafficking enables their use in various antiviral systems for improved targeting efficiency and treatment efficacy.

Continued Visibility of COVID-19 Article Removals.

Objective: The coronavirus disease 2019 pandemic has produced an unprecedented amount of scientific research as well as a high number of article retractions. Social and news media have been used to disseminate scientific research, and this can include retracted or withdrawn research. This risks the persistence of low-quality research and may contribute to controversial ideas or conspiracy theories.

Collagen-Binding Peptide-Enabled Supramolecular Hydrogel Design for Improved Organ Adhesion and Sprayable Therapeutic Delivery.

Spraying serves as an attractive, minimally invasive means of administering hydrogels for localized delivery, particularly due to high-throughput deposition of therapeutic depots over an entire target site of uneven surfaces. However, it remains a great challenge to design systems capable of rapid gelation after shear-thinning during spraying and adhering to coated tissues in wet, physiological environments. We report here on the use of a collagen-binding peptide to enable a supramolecular design of a biocompatible, bioadhesive, and sprayable hydrogel for sustained release of therapeutics.

Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval.

Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, et al. Anifrolumab, an anti-interferon-α receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol 2017;69:376-86.

The context of the ribosome binding site in mRNAs defines specificity of action of kasugamycin, an inhibitor of translation initiation.

Kasugamycin (KSG) is an aminoglycoside antibiotic widely used in agriculture and exhibits considerable medical potential. Previous studies suggested that KSG interferes with translation by blocking binding of canonical messenger RNA (mRNA) and initiator transfer tRNA (tRNA) to the small ribosomal subunit, thereby preventing initiation of protein synthesis. Here, by using genome-wide approaches, we show that KSG can interfere with translation even after the formation of the 70S initiation complex on mRNA, as the extent of KSG-mediated translation inhibition correlates with increased occupancy of start codons by 70S ribosomes.

Alternative publication metrics in the time of COVID-19.

Alternative metrics are unique bibliometrics comprising social, news, and other sources of media outside of traditional academic citations. Some have suggested that these metrics can complement traditional metrics of research impact, including public engagement with research. The COVID-19 pandemic provides a unique opportunity to study alternative metrics and the dissemination of scientific research given the heightened academic and public interest.

Propagation-Instigated Self-Limiting Polymerization of Multiarmed Amphiphiles into Finite Supramolecular Polymers.

A fundamental goal in the noncovalent synthesis of ordered supramolecular polymers (SPs) is to achieve precise control over their size and size distribution; however, the reversible nature of noncovalent interactions often results in formation of living SPs with high dispersity in length. We report here on the self-limiting supramolecular polymerization (SPZ) of a series of multiarmed amphiphiles with propagation-attenuated reactivities that can automatically terminate the polymerization process, enabling effective control in both lengths and polydispersity. Through incorporating multiarmed oligoethylene-glycol (OEG) onto a quadratic aromatic segment, the lengths of the resultant SPs can be tuned from ∼1 μm to 130 and 50 nm with a polydispersity index of ∼1.

Therapeutic supramolecular tubustecan hydrogel combined with checkpoint inhibitor elicits immunity to combat cancer.

The clinical benefit of PD-1/PD-L1 blockade immunotherapy is substantially restricted by insufficient infiltration of T lymphocytes into tumors and compromised therapeutic effects due to immune-related adverse events following systemic administration. Some chemotherapeutic agents have been reported to trigger tumor-associated T cell responses, providing a promising strategy to achieve potent immune activation in a synergistic manner with PD-1 blockade immunotherapy. In light of this, a localized chemoimmunotherapy system was developed using an anti-cancer drug-based supramolecular polymer (SP) hydrogel to "re-edit" the host's immune system to combat cancer.

Academic Journal Retractions and the COVID-19 Pandemic.

The 2020 COVID-19 pandemic has produced an unprecedented amount of scientific research, with over 100,000 articles on the SARS-COV2 virus or the associated pandemic published within the first year. To effectively disseminate such a large volume of research, some academic journal publishers altered their review criteria, and many articles were made available before undergoing a traditional review process. However, with this rapid influx of information, multiple COVID-19 articles have been retracted or withdrawn.

Internal structure of ultralow-crosslinked microgels: From uniform deswelling to phase separation.

We perform small angle neutron scattering on ultralow-crosslinked microgels and find that while in certain conditions both the particle size and the characteristic internal length scale change in unison, in other instances this is not the case. We show that nonuniform deswelling depends not only on particle size, but also on the particular way the various contributions to the free energy combine to result in a given size. Only when polymer-solvent demixing strongly competes with ionic or electrostatic effects do we observe nonuniform behavior, reflecting internal microphase separation.