Evolut R

Amyloid plaques composed of fibrils of misfolded Aβ peptides are pathological hallmarks of Alzheimer's disease (AD). Aβ fibrils are polymorphic in their tertiary and quaternary molecular structures. This structural polymorphism may carry different pathologic potencies and can putatively contribute to clinical phenotypes of AD. Therefore, mapping of structural polymorphism of Aβ fibrils and structural evolution over time is valuable to understanding disease mechanisms. Here, we investigated how Aβ fibril structures in situ differ in Aβ plaque of different mouse models expressing familial mutations in the AβPP gene...

Metazoan species depict a wide spectrum of regeneration ability which calls into question the evolutionary origins of the underlying processes. Since species with high regeneration ability are widely distributed throughout metazoans, there is a possibility that the metazoan ancestor had an underlying common molecular mechanism. Early metazoans like sponges possess high regenerative ability, but, due to the large differences they have with Cnidaria and Bilateria regarding symmetry and neuronal systems it can be inferred that this regenerative ability is different...

This study elucidates the mass transfer mechanism of myoglobin (Mb) within a single silica particle with a 50 nm pore size at various pH levels (6.0, 6.5, 6.8, and 7.0). Investigation of Mb distribution ratio (R) and distribution kinetics was conducted using absorption microspectroscopy. The highest R was observed at pH 6.8, near the isoelectric point of Mb, as the electrostatic repulsion between Mb molecules on the silica surface decreased. The time-course absorbance of Mb in the silica particle was rigorously analyzed based on a first-order reaction, yielding the intraparticle diffusion coefficient of Mb (Dp )...

Mn-doped Bi3 O4 Br has been synthesized using a solvothermal route. The undoped Bi3 O4 Br and Mn-Bi3 O4 Br materials possess orthorhombic unit cells with two distinct Bi sites forming a layered atomic arrangement. The shift in the (020) plane in the powder X-ray diffraction (PXRD) pattern confirms Mn-doping in the Bi3 O4 Br lattice. Elemental mapping indicated 7% Mn doping in the Bi3 O4 Br lattice structure. A core-level X-ray photoelectron study (XPS) indicates the presence of BiIII and MnII valence-states in Mn-Bi3 O4 Br...

Stratospheric aerosol injection (SAI) is proposed as a means of reducing global warming and climate change impacts. Similar to aerosol enhancements produced by volcanic eruptions, introducing particles into the stratosphere would reflect sunlight and reduce the level of warming. However, uncertainties remain about the roles of nucleation mechanisms, ionized molecules, impurities (unevaporated residuals of injected precursors), and ambient conditions in the generation of SAI particles optimally sized to reflect sunlight...

A global decline in seagrass populations has led to renewed calls for their conservation as important providers of biogenic and foraging habitat, shoreline stabilization and carbon storage. Eelgrass ( Zostera marina ) occupies the largest geographic range among seagrass species spanning a commensurately broad spectrum of environmental conditions. In Canada, eelgrass is managed as a single phylogroup despite occurring across three oceans and a range of ocean temperatures and salinity gradients. Previous research has focused on applying relatively few markers to reveal population structure of eelgrass, whereas a whole-genome approach is warranted to investigate cryptic structure among populations inhabiting different ocean basins and localized environmental conditions...

The journey of clinical research in India spans centuries, marked by significant milestones and advancements in scientific, ethical, and regulatory domains. From early trials conducted by pioneers like James Lind to modern standards shaped by landmark events such as the Nuremberg Code and the adoption of Good Clinical Practice guidelines, India's progression reflects a commitment to ethical conduct and patient welfare. The Indian Council of Medical Research (ICMR) has played a pivotal role in this evolution, establishing national research centers and ethical committees to oversee biomedical research...

The origin of paired appendages became one of the most important adaptations of vertebrates, allowing them to lead active lifestyles and explore a wide range of ecological niches. The basic form of paired appendages in evolution is the fins of fishes. The problem of paired appendages has attracted the attention of researchers for more than 150 years. During this time, a number of theories have been proposed, mainly based on morphological data, two of which, the Balfour-Thacher-Mivart lateral fold theory and Gegenbaur's gill arch theory, have not lost their relevance...

The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for innovative therapies with high genetic barriers to resistance. Therefore, there is pronounced interest in identifying new pharmacological targets in the SARS-CoV-2 viral life cycle. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. In this study, we investigate the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs)...

RNA viruses, like SARS-CoV-2, depend on their RNA-dependent RNA polymerases (RdRp) for replication, which is error prone. Monitoring replication errors is crucial for understanding the virus's evolution. Current methods lack the precision to detect rare de novo RNA mutations, particularly in low-input samples such as those from patients. Here we introduce a targeted accurate RNA consensus sequencing method (tARC-seq) to accurately determine the mutation frequency and types in SARS-CoV-2, both in cell culture and clinical samples...

In the species-rich family Vespertilionidae, vesper yellow bats in the genus Rhogeessa include eleven species, three of them endemic to Mexico. These insectivorous bats provide important ecosystem services, including pest control. Even though some aspects of their biology are well- known, only a few genomic resources are available for these species, which limits our understanding of their biology. In this study, we assembled and annotated the mitochondrial genome of four species: R. aenea, R. genowaysi, R. mira, and R...

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection (RTI). METHODS: Prospective, multicenter, non-inferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus (RV), negative for a bacterial pathogen and had a favorable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy...

Electrochemical liquid electron microscopy has revolutionized our understanding of nanomaterial dynamics by allowing for direct observation of their electrochemical production. This technique, primarily applied to inorganic materials, is now being used to explore the self-assembly dynamics of active molecular materials. Our study examines these dynamics across various scales, from the nanoscale behavior of individual fibers to the micrometer-scale hierarchical evolution of fiber clusters. To isolate the influences of the electron beam and electrical potential on material behavior, we conducted thorough beam-sample interaction analyses...

Where there are bacteria, there will be bacteriophages. These viruses are known to be important players in shaping the wider microbial community in which they are embedded, with potential implications for human health. On the other hand, bacteria possess a range of distinct immune mechanisms that provide protection against bacteriophages, including the mutation or complete loss of the phage receptor, and CRISPR-Cas adaptive immunity. While our previous work showed how a microbial community may impact phage resistance evolution, little is known about the inverse, namely how interactions between phages and these different phage resistance mechanisms affect the wider microbial community in which they are embedded...

The selective pressure of pathogen-host symbiosis drives adaptations. How these interactions shape the metabolism of pathogens is largely unknown. Here, we use comparative genomics to systematically analyse the metabolic networks of oomycetes, a diverse group of eukaryotes that includes saprotrophs as well as pathogens of animal- and plant pathogens, the latter causing devastating diseases with significant economic and/or ecological impact. In our analyses of 44 oomycete species, we uncover considerable variation in metabolism that can be linked to lifestyle differences...

Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis and chronic obstructive pulmonary disease. Prolonged infection allows accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonising upper airway environments. Here, we model this process using an experimental evolution approach. P. aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments...

BACKGROUND: Neisseria gonorrhoeae (Ng) is a public health priority due to the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration (MIC) and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), ciprofloxacin (CIP) over a 10-year period. METHODS: Retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral and pharyngeal samples at San Raffaele Scientific Institute, between September 2012-February 2023...

Homology in vertebrate body plans is traditionally ascribed to the high-level conservation of regulatory components within the genetic programs governing them, particularly during the "phylotypic stage." However, advancements in embryology and molecular phylogeny have unveiled the dynamic nature of gene repertoires responsible for early development. Notably, the Nodal and Lefty genes, members of the transforming growth factor-beta superfamily producing intercellular signaling molecules and crucial for left-right (L-R) symmetry breaking, exhibit distinctive features within their gene repertoires...

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4...

The complex interactions were performed among non-pharmaceutical interventions, vaccinations, and hosts for all epidemics in mainland China during the spread of COVID-19. Specially, the small-scale epidemic in the city described by SVEIR model was less found in the current studies. The SVEIR model with control was established to analyze the dynamical and epidemiological features of two epidemics in Jinzhou City led by Omicron variants before and after Twenty Measures. In this study, the total population ( N ) of Jinzhou City was divided into five compartments: the susceptible ( S ), the vaccinated ( V ), the exposed ( E ), the infected ( I ), and the recovered ( R )...