Leveraging structure-informed machine learning for fast steric zipper propensity prediction across whole proteomes.

Predicting the amyloid fold and the propensity of peptide segments to adopt amyloid-like structures remain a challenge. However, recent progress has facilitated structure-based prediction of steric zipper propensity and the use of machine learning to accelerate the calculation of predictive models across many scientific areas. Leveraging these advances, we have developed a new approach for rapid proteome-wide assessment of zipper profiles that is informed by four million steric zipper predictions collected over ten years.

Combining MicroED and native mass spectrometry for structural discovery of enzyme-small molecule complexes.

With the goal of accelerating the discovery of small molecule-protein complexes, we leverage fast, low-dose, event-based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This approach, which we term electron diffraction with native mass spectrometry (ED-MS), allows assignment of protein target structures bound to ligands with data obtained from crystal slurries soaked with mixtures of known inhibitors and crude biosynthetic reactions. This extends to libraries of printed ligands dispensed directly onto TEM grids for later soaking with microcrystal slurries, and complexes with noncovalent ligands.

Minimizing Instability in Isolated Head and Liner Exchange With the Direct Anterior Approach Using a Capsular-Sparing Technique.

Background: Dislocation is a common complication after head and liner exchange. Although surgical approach has been shown to influence instability rate following primary total hip replacement, the same has not been demonstrated for head and liner exchange. The effect of additional soft tissue release to achieve exposure in revision surgery has been implicated in this finding.

Engineering PdAu/CeO Alloy/Oxide Interfaces for Selective Methane-to-Methanol Conversion with Water.

The direct conversion of methane-to-methanol remains a critical challenge in methane valorization. In this study, we unveil the crucial role of PdAu/CeO catalysts in enabling selective methane transformation under mild conditions, using only water as the sole oxidant. Through a combination of experimental techniques, including XPS and catalytic testing, alongside density functional theory (DFT) calculations, we demonstrate that a PdAu/CeO catalyst, which predominantly exposes isolated Pd atoms, achieves remarkable methanol selectivity (∼80%) at 500 K with a 1:1 methane-to-water ratio.

MgO Nanostructures on Au(111) as Catalysts for Low-Temperature Methane Activation and C-C Coupling.

The selective conversion of methane (CH) under mild conditions remains challenging due to strong C-H bonds and catalyst coking. We systematically investigated submonolayer MgO nanostructures on Au(111), where two-dimensional (2D) MgO islands with stable Mg-O-Au interfaces catalyze low-temperature CH activation and C-C coupling. Upon CH exposure at 300 K, surface-bound CH and CH intermediates formed and persisted postevacuation, indicating robust CH-O-Mg linkages.

Application of Ternary Deep Eutectic Solvent in Liquid-Phase Microextraction Techniques.

In recent years, deep eutectic solvents (DESs) have experienced widespread growth due to their potential use as "green solvents" replacing traditional organic solvents. DESs present important advantages such as easy preparation, high affinity, low toxicity and accessibility of their components. Therefore, they have been applied as extracting agents in liquid phase microextraction techniques.

In situ insights into antibody-mediated neutralization of a pre-fusion Junin virus glycoprotein complex.

A transmembrane glycoprotein complex (GPC) decorates the Junin mammarenavirus (JUNV) that causes New World hemorrhagic fevers. We leveraged single-particle cryoelectron microscopy (cryo-EM) to image the full-length JUNV GPC directly on pseudotyped virus (PV) membranes and bound by two JUNV-neutralizing antibodies: Candid#1 vaccine-elicited CR1-28 and J199, a potent therapeutic against Argentine hemorrhagic fever (AHF). The 3.

Modulation of Gut Microbiota by Whole Encapsulated Brown Seaweed () in Overweight Subjects: A Randomized Double-Blind Placebo-Controlled Trial.

: Brown seaweeds, such as , are a promising source of dietary fiber. However, in vivo evidence regarding the effects of intake on the human gut microbiota remains limited. This study aimed to evaluate the impact of daily consumption on the gut microbiota composition and short-chain fatty acid production in overweight adults.

XPO1 R749Q Mutations Co-occur with POLE Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance.

Unlabelled: Exportin-1 (XPO1) is a nuclear export receptor that is essential for cell survival. Previous genomic analyses have identified recurrent XPO1 hotspot mutations in cancer. In this study, we conducted a large-scale genomic analysis of 217,570 patients with cancer to identify and characterize XPO1 variants from real-world patient tumors.

CO Adsorption and Hydrogenation on Inverse InO/Cu(111) Catalysts: Active Role of the Oxide-Metal Interface.

The direct conversion of carbon dioxide (CO) into methanol via hydrogenation is essential for industrial applications. Recent studies on catalysts that contain an inverse oxide/metal configuration have shown very good catalytic performance for the CO hydrogenation to methanol process. In this study, we investigated the behavior of indium oxide-Cu(111) interfaces under pure CO and CO/H mixtures by using synchrotron-based ambient-pressure X-ray photoelectron spectroscopy (AP-XPS).

Enhancing Acidic Oxygen Evolution Activity by Controlling Oxidation State of Iridium.

Iridium oxides with high oxidation states have been reported to be effective in enhancing the acidic oxygen evolution reaction (OER) performance. Herein, we develop ultrasmall IrO nanoparticles (NPs) over titanium nitride (TiN), which undergoes surface oxidation under oxidative conditions to form oxygen-modified TiN (oxi-TiN), enabling the formation of highly oxidized Ir (δ > 4). This IrO/oxi-TiN catalyst delivers higher Ir mass activity than commercial IrO, while comparable stability is maintained.

Structural insights into functional regulation of the human CPEB3 prion by an amyloid-forming segment.

The cytoplasmic polyadenylation-element-binding-protein-3 (CPEB3) is a functional prion thought to modulate protein synthesis and enable consolidation of long-term memory in neurons. We report a cryoelectron microscopy (cryo-EM) structure of amyloid fibrils grown in vitro from the first prion-like domain of human CPEB3 (hCPEB3), revealing their ordered 49-residue core, spanning L103 to F151. CPEB3 lacking that segment coalesces into abnormal puncta in cells compared to wild-type CPEB3, localizes away from dormant p-bodies and toward stress granules, and lacks the ability to influence protein synthesis in neurons.

Structural basis for L-isoaspartyl-containing protein recognition by the PCMTD1 cullin-RING E3 ubiquitin ligase.

A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging organismal survival. While repair through methylation by PCMT1 has been previously shown to suppress L-isoaspartyl accumulation, we provide an additional mechanism for L-isoaspartyl maintenance through PCMTD1, a cullin-RING ligase (CRL).

Determination of glycerol in canola oil-based biodiesel by micellar electrokinetic chromatography.

A micellar electrokinetic chromatography (MEKC) methodology was optimized for the indirect determination of glycerol based on formaldehyde formation and the use of 3-methyl-2-benzothiazolinone hydrazone (MBTH) as a derivatizing agent. A Taguchi experimental design matrix L(3) was used to evaluate the critical variables and maximize the separation efficiency. Under optimum conditions of [SDS] 60.

Visualizing Size-Dependent Dynamics of CeO{100}-Supported CoO Nanoparticles Under CO Hydrogenation Conditions.

Carbon dioxide is a major greenhouse gas. In order to optimize processes focused on its chemical valorization, one needs detailed information about the effects of CO and/or CO/H mixtures on the structure and morphology of metal/oxide catalysts. In this study, the evolution of a catalyst with cobalt supported on CeO-cube nanostructures under CO hydrogenation conditions was investigated by using a set of in situ characterization techniques (X-ray absorption fine structure, X-ray diffraction, diffuse reflectance infrared Fourier transform spectroscopy, and environmental transmission electron microscopy (TEM)).

Biosourced Functional Hydroxybenzoate--Lactide Polymers with Antimicrobial Activity.

Antimicrobial resistance is an urgent global health challenge, and compounds that address this issue have attracted significant attention. In particular, bioderived molecules that possess natural antimicrobial properties can be useful to prepare active macromolecules that are degradable. In this work, a 4-(methyl/allyl/benzyl)oxy-6-(H/alkyl)-2-oxy-benzoate--lactide-based polymer library was designed and studied for antimicrobial activity.

Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors.

E-64 is an irreversible cysteine protease inhibitor prominently used in chemical biology and drug discovery. Here we uncover a nonribosomal peptide synthetase-independent biosynthetic pathway for E-64, which is widely conserved in fungi. The pathway starts with epoxidation of fumaric acid to the warhead (2S,3S)-trans-epoxysuccinic acid with an Fe(II)/α-ketoglutarate-dependent oxygenase, followed by successive condensation with an L-amino acid by an adenosine triphosphate grasp enzyme and with an amine by the fungal example of amide bond synthetase.

Imaging the Progression of Radiolytic Damage in Molecular Crystals with Scanning Nanobeam Electron Diffraction.

Almost every electron microscopy experiment is fundamentally limited by radiation damage. Nevertheless, little is known about the onset and progression of radiolysis in beam-sensitive materials. Here we apply ambient-temperature scanning nanobeam electron diffraction to record simultaneous dual-space movies of organic and organometallic nanocrystals at sequential stages of beam-induced radiolytic decay.

Motor Recovery After Surgical Neurolysis in Brachial Plexus Neuropathy: A Case Study and Systematic Review.

The aim of this study is to assess the motor outcomes of patients undergoing surgical neurolysis and to conduct a comprehensive review of existing literature to ascertain the efficacy and utility of this technique. Surgical neurolysis is a procedure designed to liberate an injured nerve from scar tissue or adjacent structure, thereby facilitating nerve regeneration in cases of brachial plexus neuropathy (BPN). This study presents a case series of patients diagnosed with BPN who underwent surgical neurolysis.

Brucella suis Infection in Cardiac Implantable Device of Man Exposed to Feral Swine Meat, Florida, USA.

Brucella suis infection in the United States is typically from feral swine exposure. We describe a case of B. suis cardiac implantable device infection in a man exposed to meat and blood from feral swine in Florida, USA.

Combining MicroED and native mass spectrometry for structural discovery of enzyme-biosynthetic inhibitor complexes.

With the goal of accelerating the discovery of small molecule-protein complexes, we leverage fast, low-dose, event based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This approach resolves structures of the epoxide-based cysteine protease inhibitor, and natural product, E-64, and its biosynthetic analogs bound to the model cysteine protease, papain. The combined structural power of MicroED and the analytical capabilities of native mass spectrometry (ED-MS) allows assignment of papain structures bound to E-64-like ligands with data obtained from crystal slurries soaked with mixtures of known inhibitors, and crude biosynthetic reactions.

Design, Development, and Qualification of a Broadband Compact S-Band Antenna for a CubeSat Constellation.

An S-band antenna has been designed, developed, measured, space-qualified, and integrated into the INTA ANSER satellite constellation and the future ANSER-AT mission. This antenna will be part of the space-to-ground communication link for the constellation, which consists of one Leader and two Followers. The novel antenna, mounted on the Leader, has been designed and manufactured with materials and processes specifically tested for space.

Fast event-based electron counting for small-molecule structure determination by MicroED.

Electron counting helped realize the resolution revolution in single-particle cryoEM and is now accelerating the determination of MicroED structures. Its advantages are best demonstrated by new direct electron detectors capable of fast (kilohertz) event-based electron counting (EBEC). This strategy minimizes the inaccuracies introduced by coincidence loss (CL) and promises rapid determination of accurate structures.

Accounting for electron-beam-induced warping of molecular nanocrystals in MicroED structure determination.

High-energy electrons induce sample damage and motion at the nanoscale to fundamentally limit the determination of molecular structures by electron diffraction. Using a fast event-based electron counting (EBEC) detector, we characterize beam-induced, dynamic, molecular crystal lattice reorientations (BIRs). These changes are sufficiently large to bring reciprocal lattice points entirely in or out of intersection with the sphere of reflection, occur as early events in the decay of diffracted signal due to radiolytic damage, and coincide with beam-induced migrations of crystal bend contours within the same fluence regime and at the same illuminated location on a crystal.

Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Carbon-hydrogen (C-H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp)-H bond. In recent years, metalloenzymes have been found to perform C(sp)-H bond functionalization.