AI-Guided Inverse Design and Discovery of Recyclable Vitrimeric Polymers.

Vitrimer is a new, exciting class of sustainable polymers with healing abilities due to their dynamic covalent adaptive networks. However, a limited choice of constituent molecules restricts their property space and potential applications. To overcome this challenge, an innovative approach coupling molecular dynamics (MD) simulations and a novel graph variational autoencoder (VAE) model for inverse design of vitrimer chemistries with desired glass transition temperature (T) is presented.

Diagnostic utility of nasal methicillin-resistant polymerase chain reaction testing in head and neck infection.

In this retrospective study of adult inpatients who underwent an ear, nose, and throat (ENT) surgery with operative cultures and collection of nasal methicillin-resistant (MRSA) polymerase chain reaction (PCR), we found that MRSA nasal PCR demonstrated 100% sensitivity and a negative predictive value (NPV) of 100% when compared to operative cultures.

Evaluating the risk of data loss due to particle radiation damage in a DNA data storage system.

DNA data storage is a potential alternative to magnetic tape for archival storage purposes, promising substantial gains in information density. Critical to the success of DNA as a storage media is an understanding of the role of environmental factors on the longevity of the stored information. In this paper, we evaluate the effect of exposure to ionizing particle radiation, a cause of data loss in traditional magnetic media, on the longevity of data in DNA data storage pools.

The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.

What are the Desired Characteristics of Calibration Sets? Identifying Correlates on Long Form Scientific Summarization.

Summarization models often generate text that is poorly calibrated to quality metrics because they are trained to maximize the likelihood of a single reference (MLE). To address this, recent work has added a calibration step, which exposes a model to its own ranked outputs to improve relevance or, in a separate line of work, contrasts positive and negative sets to improve faithfulness. While effective, much of this work has focused on to generate and optimize these sets.

Ot2Rec: A semi-automatic, extensible, multi-software tomographic reconstruction workflow.

Electron cryo-tomography is an imaging technique for probing 3D structures with at the nanometer scale. This technique has been used extensively in the biomedical field to study the complex structures of proteins and other macromolecules. With the advancement in technology, microscopes are currently capable of producing images amounting to terabytes of data per day, posing great challenges for scientists as the speed of processing of the images cannot keep up with the ever-higher throughput of the microscopes.

Structural dissection of two redox proteins from the shipworm symbiont Teredinibacter turnerae.

The discovery of lytic polysaccharide monooxygenases (LPMOs), a family of copper-dependent enzymes that play a major role in polysaccharide degradation, has revealed the importance of oxidoreductases in the biological utilization of biomass. In fungi, a range of redox proteins have been implicated as working in harness with LPMOs to bring about polysaccharide oxidation. In bacteria, less is known about the interplay between redox proteins and LPMOs, or how the interaction between the two contributes to polysaccharide degradation.

A protocol for cryogenic volumetric imaging using serial plasma FIB/SEM.

Cryogenic volumetric imaging using serial plasma focused ion beam scanning electron microscopy (serial pFIB/SEM) is a new and exciting correlative volume electron microscopy (vEM) technique. It enables visualization of un-stained, cryogenically immobilized cells and tissues with ∼20-50nm resolution and a field of view of ∼10-30μm resulting in near-native state imaging and the possibility of microscale, mesoscale and nanoscale correlative imaging. We have written a detailed protocol for optimization of FIB and SEM parameters to reduce imaging artefacts and enable downstream computational processing and analysis.

Spatially Selective Electrochemical Cleavage of a Polymerase-Nucleotide Conjugate.

Novel enzymatic methods are poised to become the dominant processes for de novo synthesis of DNA, promising functional, economic, and environmental advantages over the longstanding approach of phosphoramidite synthesis. Before this can occur, however, enzymatic synthesis methods must be parallelized to enable production of multiple DNA sequences simultaneously. As a means to this parallelization, we report a polymerase-nucleotide conjugate that is cleaved using electrochemical oxidation on a microelectrode array.

Structural atlas of a human gut crassvirus.

CrAssphage and related viruses of the order Crassvirales (hereafter referred to as crassviruses) were originally discovered by cross-assembly of metagenomic sequences. They are the most abundant viruses in the human gut, are found in the majority of individual gut viromes, and account for up to 95% of the viral sequences in some individuals. Crassviruses are likely to have major roles in shaping the composition and functionality of the human microbiome, but the structures and roles of most of the virally encoded proteins are unknown, with only generic predictions resulting from bioinformatic analyses.

Cryo-plasma FIB/SEM volume imaging of biological specimens.

Serial focussed ion beam scanning electron microscopy (FIB/SEM) enables imaging and assessment of subcellular structures on the mesoscale (10 nm to 10 µm). When applied to vitrified samples, serial FIB/SEM is also a means to target specific structures in cells and tissues while maintaining constituents' hydration shells for in situ structural biology downstream. However, the application of serial FIB/SEM imaging of non-stained cryogenic biological samples is limited due to low contrast, curtaining, and charging artefacts.

Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation.

Phosphorylation of SARS-CoV-2 nucleoprotein recruits human cytosolic 14-3-3 proteins playing a well-recognized role in replication of many viruses. Here we use genetic code expansion to demonstrate that 14-3-3 binding is triggered by phosphorylation of SARS-CoV-2 nucleoprotein at either of two pseudo-repeats centered at Ser197 and Thr205. According to fluorescence anisotropy measurements, the pT205-motif,presentin SARS-CoV-2 but not in SARS-CoV, is preferred over the pS197-motif by all seven human 14-3-3 isoforms, which collectively display an unforeseen pT205/pS197 peptide binding selectivity hierarchy.

Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.

Background: Iron deficiency (Fe) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fe on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fe into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fe and established variables of prognostic importance in PAH.

The DNA polymerase of bacteriophage YerA41 replicates its T-modified DNA in a primer-independent manner.

Yersinia phage YerA41 is morphologically similar to jumbo bacteriophages. The isolated genomic material of YerA41 could not be digested by restriction enzymes, and used as a template by conventional DNA polymerases. Nucleoside analysis of the YerA41 genomic material, carried out to find out whether this was due to modified nucleotides, revealed the presence of a ca 1 kDa substitution of thymidine with apparent oligosaccharide character.

Scaling DNA data storage with nanoscale electrode wells.

Synthetic DNA is an attractive medium for long-term data storage because of its density, ease of copying, sustainability, and longevity. Recent advances have focused on the development of new encoding algorithms, automation, preservation, and sequencing technologies. Despite progress in these areas, the most challenging hurdle in deployment of DNA data storage remains the write throughput, which limits data storage capacity.

Facile synthesis of insulin fusion derivatives through sortase A ligation.

Insulin derivatives such as insulin detemir and insulin degludec are U.S. Food and Drug Administration (FDA)-approved long-acting insulin currently used by millions of people with diabetes.

C-type cytochrome-initiated reduction of bacterial lytic polysaccharide monooxygenases.

The release of glucose from lignocellulosic waste for subsequent fermentation into biofuels holds promise for securing humankind's future energy needs. The discovery of a set of copper-dependent enzymes known as lytic polysaccharide monooxygenases (LPMOs) has galvanised new research in this area. LPMOs act by oxidatively introducing chain breaks into cellulose and other polysaccharides, boosting the ability of cellulases to act on the substrate.

Effects of double-dose algebra on college persistence and degree attainment.

In 2003, Chicago Public Schools introduced double-dose algebra, requiring two periods of math-one period of algebra and one of algebra support-for incoming ninth graders with eighth-grade math scores below the national median. Using a regression discontinuity design, earlier studies showed promising results from the program: For median-skill students, double-dose algebra improved algebra test scores, pass rates, high school graduation rates, and college enrollment. This study follows the same students 12 y later.

The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins.

The coronavirus nucleocapsid protein (N) controls viral genome packaging and contains numerous phosphorylation sites located within unstructured regions. Binding of phosphorylated SARS-CoV N to the host 14-3-3 protein in the cytoplasm was reported to regulate nucleocytoplasmic N shuttling. All seven isoforms of the human 14-3-3 are abundantly present in tissues vulnerable to SARS-CoV-2, where N can constitute up to ~1% of expressed proteins during infection.

Identification of human remains using Rapid DNA analysis.

Rapid identification of human remains following mass casualty events is essential to bring closure to family members and friends of the victims. Unfortunately, disaster victim identification, missing persons identification, and forensic casework analysis are often complicated by sample degradation due to exposure to harsh environmental conditions. Following a mass disaster, forensic laboratories may be overwhelmed by the number of dissociated portions that require identification and reassociation or compromised by the event itself.

8-Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis.

There is an urgent need for new treatments effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. The 8-hydroxyquinoline series is a privileged scaffold with anticancer, antifungal, and antibacterial activities. We conducted a structure-activity relationship study of the series regarding its antitubercular activity using 26 analogs.

Anodic Cyclization Reactions and the Mechanistic Strategies That Enable Optimization.

Oxidation reactions are powerful tools for synthesis because they allow us to reverse the polarity of electron-rich functional groups, generate highly reactive intermediates, and increase the functionality of molecules. For this reason, oxidation reactions have been and continue to be the subject of intense study. Central to these efforts is the development of mechanism-based strategies that allow us to think about the reactive intermediates that are frequently central to the success of the reactions and the mechanistic pathways that those intermediates trigger.