Publications by authors named "McKENNA R"

Goose parvovirus (GPV) is an etiological agent of Derzsy's disease, afflicting geese and Muscovy ducks worldwide. Its high mortality rate among goslings and ducklings causes large losses to the waterfowl industry. Toward molecular and structural characterization, virus-like particles (VLPs) of GPV were produced, and the capsid structure was determined by cryogenic electron microscopy (cryo-EM) at a resolution of 2.

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are ssDNA plant viruses whose control has both economical and agricultural importance. Their capsids assemble into two distinct architectural forms: (i) a T = 1 icosahedral and (ii) a unique twinned quasi-isometric capsid. Described here are the high-resolution structures of both forms of the maize streak virus using cryo-EM.

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Objective: Physician assistants (PAs) are employed in endocrinology, but little is known about their roles and activities. The study aimed to assess PAs' employment characteristics in endocrinology compared to those in all other specialties.

Methods: This descriptive observational study used the 2022 National Commission on Certification of PAs dataset.

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Object: Physician associates (PAs) and nurse practitioners (NPs) are distributed across 70 medical and surgical specialties. A central role is to provide outpatient care. Urology is a significant employer of PAs and NPs, but their scope of practice in the ambulatory setting needs to be better delineated.

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The application of adeno-associated virus (AAV) vectors in human gene therapies requires reproducible and homogeneous preparations for clinical efficacy and safety. For the AAV production process, often scalable affinity chromatography columns are utilized, such as the POROS CaptureSelect AAVX affinity resin, during downstream processing to ensure highly purified AAV vectors. The AAVX ligand is based on a camelid single-domain antibody capturing a wide range of recombinant AAV capsids.

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It has been previously established that breast cancer cells exhibit high expression of the monocarboxylate (lactate) transporters (MCT1 and/or MCT4) and carbonic anhydrase IX (CAIX) and form a functional metabolon for proton-coupled lactate export, thereby stabilizing intracellular pH. CD147 is the MCT accessory protein that facilitates the creation of the MCT/CAIX complex. This study describes how the small molecule Beta-Galactose 2C (BGal2C) blocks the physical and functional interaction between CAIX and either MCT1 or MCT4 in Xenopus oocytes, which reduces the rate of proton and lactate flux with an IC of ~90 nM.

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Background: The E-cadherin, α- and β-Catenin interaction at the cell adherens junction plays a key role in cell adhesion; alteration in the expression and function of these genes are associated with disease progression in several solid tumors including prostate cancer. The membranous β-Catenin is dynamically linked to the cellular cytoskeleton through interaction with α-Catenin at amino acid positions threonine 120 (T120) to 151 of β-Catenin. Nuclear presence of α-Catenin modulates the sensitivity of cells to DNA damage.

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Article Synopsis
  • - Human alpha-defensin antimicrobial peptides, specifically human neutrophil peptide 1 (HNP1) and human defensin 5 (HD5), significantly inhibit the effectiveness of adeno-associated virus (AAV2) vectors used in gene therapy by blocking infection and preventing the virus from reaching the nucleus.
  • - HD5 stops AAV2 from binding to cells, while HNP1 does not, but both defensins interfere with key viral processes that are necessary for the virus's success in infecting cells.
  • - These findings suggest a shared mechanism of action among alpha-defensins in neutralizing various non-enveloped viruses, which could lead to advancements in developing more effective gene therapy vectors that can overcome innate immune barriers.
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In 2022, the World Health Organization (WHO) and International Consensus Classification (ICC) recognized as an entity-defining alteration in myeloid neoplasms, yet with differing criteria that could lead to discrepant diagnoses and affect clinical trial eligibility. We studied 67 patients with mutant myeloid neoplasms, reclassifying them using both criteria. While most cases fulfill the criteria for mutant defined entities, most discrepancies were found in cases with ≥20% blasts.

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  • - Bufaviruses (BuV) are non-enveloped, single-stranded DNA viruses linked to acute diarrhea, necessitating further molecular and structural studies due to limited treatment options and understanding of their disease mechanisms.
  • - The study shows that the BuV1 capsid binds to terminal sialic acid (SIA) glycans, and cryo-electron microscopy reveals how SIA binds on the capsid surface, with identifying conserved residues crucial for this interaction across all human BuVs.
  • - The research provides structural insights into BuV1 capsids under different pH levels, illustrating structural changes during virus escape from endo-lysosomes, which may aid in developing antiviral treatments targeting the SIA binding site.
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Hydrogen will play a key role in decarbonizing economies. Here, we quantify the costs and environmental impacts of possible large-scale hydrogen economies, using four prospective hydrogen demand scenarios for 2050 ranging from 111-614 megatonne H year. Our findings confirm that renewable (solar photovoltaic and wind) electrolytic hydrogen production generates at least 50-90% fewer greenhouse gas emissions than fossil-fuel-based counterparts without carbon capture and storage.

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Many phytopathogenic bacteria require a type III secretion system (TTSS) to activate effector-triggered immunity (ETI). We identified a calcium-binding protein, EfhX, in the citrus pathogen subsp. that does not require a TTSS to activate reactive oxygen species (ROS) and elicit a hypersensitive reaction (HR) in tomato leaves following infection.

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  • * Laboratory tests confirmed the presence of a low-pathogenicity avian influenza virus (LPAIV) subtype H6N1, affecting 15 premises in Northern Ireland and spreading to 13 in the Republic of Ireland and six in Great Britain.
  • * The outbreak resulted in the culling of over 2 million birds to control the spread, highlighting the significant economic consequences and the need for swift action during LPAIV outbreaks.
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(SpV4) is a bacteriophage of the , which packages circular ssDNA within non-enveloped T = 1 icosahedral capsids. It infects spiroplasmas, which are known pathogens of honeybees. Here, the structure of the SpV4 virion is determined using cryo-electron microscopy to a resolution of 2.

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Patients who have had fractures are at increased risk for a second or fragility fracture. A fracture liaison service (FLS), often staffed or led by physician associates/assistants or NPs, may help reduce second fractures and patient mortality. This article reviews FLSs and their effectiveness.

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  • This study evaluates the clinical features and outcomes of acute cannabis toxicity versus acute synthetic cannabinoid receptor agonist toxicity in European emergency departments from 2013-2020.
  • Using data from the European Drug Emergencies Network Plus, researchers analyzed 2,657 cases of cannabis exposure and 503 cases of synthetic cannabinoid exposure to compare their effects.
  • The findings indicate that synthetic cannabinoid exposures are linked to more severe neuropsychiatric symptoms, while cannabis exposures are associated with cardiovascular issues.
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  • KSHV's viral interferon regulatory factors (vIRFs) disrupt cell signaling to support viral cancer development and hinder immune responses, but their specific roles in gene regulation are unclear.
  • *A study comparing the protein structures and gene regulation of four vIRFs showed they have similar structures but regulate different sets of genes.
  • *The research indicates that vIRF1's DNA-binding domain is crucial for controlling its target genes, suggesting that vIRFs have specialized functions despite their structural similarities.*
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Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection.

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  • AAV serotypes from primates are being utilized as gene therapy vectors in humans, but their evolutionary mechanics, particularly genetic recombination, are not well understood.
  • Natural AAV capsid genes were analyzed to identify positively selected sites that are significant to their structure and function.
  • The study found that while one site on the AAV2 capsid showed no correlation with human immune response, another site was crucial for the virus's ability to evade human antibodies, enhancing understanding of AAV evolution and potential for gene therapy applications.
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Article Synopsis
  • Parvovirus B19 (B19V) causes various diseases in humans, and current treatment options are limited due to a lack of antivirals.
  • The virus's minor capsid protein, VP1u, contains crucial domains for infection: a receptor binding domain (RBD) for host entry and a phospholipase A2 (PLA) domain for escaping endosomes.
  • Recent studies report the structural analysis of the RBD using NMR, which confirms its stability and provides a basis for future research on developing specific antiviral drugs targeting this domain.
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Purpose: Procedures are manual technical skills clinicians perform for their patients. Family physicians (FPs) acquire these skills during residency; most are undertaken in outpatient settings. We performed a retrospective observational cohort study to describe the extent to which FPs perform the core procedures recommended by the Council of Academic Family Medicine (CAFM) and how this might have changed over time.

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Monoclonal antibodies (mAbs) are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids used as gene therapy delivery vectors. This study structurally characterizes the interactions of 21 human-derived antibodies from patients treated with the AAV9 vector, Zolgensma , utilizing high-resolution cryo-electron microscopy. The majority of the bound antibodies do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions.

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Acetylation of key Lysine residues characterizes aggregates of the microtubule-associated protein tau constituting the neuropathological hallmark of many neurodegenerative diseases, such as Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). This has led to the idea that acetylation influences tau aggregation. Using a HEK293 cell-based aggregation assay, we tested whether acetylation-mimicking substitutions (K→Q) on five AD-associated acetyl-modified sites (AcK-311, 353, 369, 370, 375) influenced its propensity to aggregate when exposed to tau seeds derived from two clinically distinctive diseases - AD and PSP.

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Objective: We hypothesized that physician associate (PA) and nurse practitioner (NP) procedural roles are expanding. We sought to describe ambulatory procedures these professionals performed in 2021 for older adults.

Study Design: Retrospective observational cohort study of Medicare Part B data.

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