The platypus () is an amphibious, egg-laying mammal of high conservation value that is found only in Australia. The zoonotic bacterium serovar Hardjo was discovered in platypuses in prior studies, but little is known about its epidemiology. Samples in the Platypus Serum Bank were tested in 2023 and the results were combined with historical records.
View Article and Find Full Text PDFPDA J Pharm Sci Technol
August 2024
Manufacturers of medical devices are legally required to carry out post-market surveillance and respond to any on-market complaints they receive about their device. When it comes to addressing use issues experienced on market, manufacturers often focus on revising the instructions for use (IFU) and labeling. One of the challenges with this approach is the potential need to re-validate via a human factors validation study, without knowing whether the changes made will be effective in addressing the identified issues.
View Article and Find Full Text PDFSolution scattering techniques, such as small- and wide-angle X-ray scattering (SWAXS), provide valuable insights into the structure and dynamics of biological macromolecules in solution. In this study, we present an approach to accurately predict solution X-ray scattering profiles at wide angles from atomic models by generating high-resolution electron density maps. Our method accounts for the excluded volume of bulk solvent by calculating unique adjusted atomic volumes directly from the atomic coordinates.
View Article and Find Full Text PDFRNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free-electron laser sources to reveal the formation and ready identification of angstrom-scale features in structured and unstructured RNAs. Previously unrecognized structural signatures of RNA secondary and tertiary structures are identified through wide-angle solution scattering experiments.
View Article and Find Full Text PDFUnlabelled: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) caused a large-scale global pandemic between 2020 and 2022. Despite efforts to understand its biological and pathogenic mechanisms, the viral impact on the neurological systems remains unclear. The main goal of this study was to quantify the neurological phenotypes induced by the SARS-CoV-2 spike protein in neurons, as measured by multiwell micro-electrode arrays (MEAs).
View Article and Find Full Text PDFDroplet injection strategies are a promising tool to reduce the large amount of sample consumed in serial femtosecond crystallography (SFX) measurements at X-ray free electron lasers (XFELs) with continuous injection approaches. Here, we demonstrate a new modular microfluidic droplet injector (MDI) design that was successfully applied to deliver microcrystals of the human NAD(P)H:quinone oxidoreductase 1 (NQO1) and phycocyanin. We investigated droplet generation conditions through electrical stimulation for both protein samples and implemented hardware and software components for optimized crystal injection at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Stanford Linac Coherent Light Source (LCLS).
View Article and Find Full Text PDFRNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free electron laser sources to reveal the formation and ready identification of Å scale features in structured and unstructured RNAs. New structural signatures of RNA secondary and tertiary structures are identified through wide angle solution scattering experiments.
View Article and Find Full Text PDFThis study reports the development of a class of eco-friendly antifouling biocides based on a cyclic dipeptide scaffold, 2,5-diketopiperazine (2,5-DKP). The lead compound cyclo(-Bip-l-Arg--Bip-l-Arg) () was synthesized in gram amounts and used to assess the compatibility with an ablation/hydration coating, efficacy against biofouling, and biodegradation. Leaching of from the coating into seawater was assessed via a rotating drum method, revealing relatively stable and predictable leaching rates under dynamic shear stress conditions (36.
View Article and Find Full Text PDFCytochrome oxidase (C O) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme group in their active sites, C O has a unique binuclear center (BNC) comprised of a copper atom (Cu ) and a heme iron, where O binds and is reduced to water. CO is a versatile O surrogate in ligand binding and escape reactions.
View Article and Find Full Text PDFAb initio modeling methods have proven to be powerful means of interpreting solution scattering data. In the absence of atomic models, or complementary to them, ab initio modeling approaches can be used for generating low-resolution particle envelopes using only solution scattering profiles. Recently, a new ab initio reconstruction algorithm has been introduced to the scientific community, called DENSS.
View Article and Find Full Text PDFNendoU from SARS-CoV-2 is responsible for the virus's ability to evade the innate immune system by cleaving the polyuridine leader sequence of antisense viral RNA. Here we report the room-temperature structure of NendoU, solved by serial femtosecond crystallography at an X-ray free-electron laser to 2.6 Å resolution.
View Article and Find Full Text PDFWith advances in X-ray free-electron lasers (XFELs), serial femtosecond crystallography (SFX) has enabled the static and dynamic structure determination for challenging proteins such as membrane protein complexes. In SFX with XFELs, the crystals are typically destroyed after interacting with a single XFEL pulse. Therefore, thousands of new crystals must be sequentially introduced into the X-ray beam to collect full data sets.
View Article and Find Full Text PDFMarine biofouling is a problem that plagues all maritime industries at vast economic and environmental cost. Previous and current methods to prevent biofouling have employed the use of heavy metals and other toxic or highly persistent chemicals, and these methods are now coming under immense regulatory pressure. Recent studies have illustrated the potential of nature-inspired tetrasubstituted 2,5-diketopiperazines (2,5-DKPs) as eco-friendly marine biocides for biofouling control.
View Article and Find Full Text PDFJ Appl Crystallogr
October 2022
Small-angle scattering (SAS) probes the size and shape of particles at low resolution through the analysis of the scattering of X-rays or neutrons passing through a solution of particles. One approach to extracting structural information from SAS data is the indirect Fourier transform (IFT). The IFT approach parameterizes the real-space pair distribution function [()] of a particle using a set of basis functions, which simultaneously determines the scattering profile [()] using corresponding reciprocal-space basis functions.
View Article and Find Full Text PDFFrancisella tularensis is an extremely infectious pathogen and a category A bioterrorism agent. It causes the highly contagious zoonosis, Tularemia. Currently, FDA approved vaccines against tularemia are unavailable.
View Article and Find Full Text PDFGun violence in places of worship (POW) has long been an issue and has been addressed repeatedly in the literature. Contextually, most of the research has been pertinent to relatively large POW, situated in an urban setting. However, rural churches have not been addressed, and they appear to have a far less defensive posture, mainly because of their remote location and the extended time required for first responders to arrive, which in turn requires a higher level of independent operation in terms of defense and medical response.
View Article and Find Full Text PDFAntimicrobial drug resistance is a looming health crisis facing us in the modern era, and new drugs are urgently needed to combat this growing problem. Synthetic mimics of antimicrobial peptides have recently emerged as a promising class of compounds for the treatment of persistent microbial infections. In the current study, we investigate five cyclic -alkylated amphiphilic 2,5-diketopiperazines against 15 different strains of bacteria and fungi, including drug-resistant clinical isolates.
View Article and Find Full Text PDFSerial femtosecond crystallography (SFX) is a powerful technique that exploits X-ray free-electron lasers to determine the structure of macro-molecules at room temperature. Despite the impressive exposition of structural details with this novel crystallographic approach, the methods currently available to introduce crystals into the path of the X-ray beam sometimes exhibit serious drawbacks. Samples requiring liquid injection of crystal slurries consume large quantities of crystals (at times up to a gram of protein per data set), may not be compatible with vacuum configurations on beamlines or provide a high background due to additional sheathing liquids present during the injection.
View Article and Find Full Text PDFExcipient Lung Disease is an inflammatory response to the intravenous administration of oral formulations of drugs and their excipients (additives). Previously described offenders include opioids and Ritalin, whose excipients, when crushed and administered intravenously, lead to inflammation and are demonstrated by centrilobular nodules and ground-glass formations on Chest Computed Tomography. In this case report, we demonstrate Chest CT findings of excipient lung disease in a patient using etizolam, a benzodiazepine derivative commonly used as an anxiolytic in Japan.
View Article and Find Full Text PDFMarine biofouling plagues all maritime industries at vast economic and environmental cost. Previous and most current methods to control biofouling have employed highly persistent toxins and heavy metals, including tin, copper, and zinc. These toxic methods are resulting in unacceptable environmental harm and are coming under immense regulatory pressure.
View Article and Find Full Text PDFJ Surg Case Rep
October 2021
We report the symptom evolution of a young female trauma patient leading to a diagnosis of fat embolism syndrome (FES). Twenty-four hours post-trauma she developed respiratory distress, followed by transient neurological compromise and later petechia. The subtle and fluctuating nature of her presentation made the diagnosis via existing clinical criteria challenging, as did the lack of specificity of thoracic computerized tomography due to the concurrent coronavirus (COVID-19) pandemic.
View Article and Find Full Text PDFChronic venous insufficiency is one of the most common benign diseases in America. For treatment, minimally invasive techniques have become the first-line option. The literature shows that these procedures are well tolerated and work effectively without leaving the patient with unaesthetic operative scars.
View Article and Find Full Text PDFTime-resolved studies of biomacromolecular crystals have been limited to systems involving only minute conformational changes within the same lattice. Ligand-induced changes greater than several angstroms, however, are likely to result in solid-solid phase transitions, which require a detailed understanding of the mechanistic interplay between conformational and lattice transitions. Here we report the synchronous behavior of the adenine riboswitch aptamer RNA in crystal during ligand-triggered isothermal phase transitions.
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