Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice.

Bourbon virus (BRBV) is an emerging tick-borne virus that can cause severe and fatal disease in humans. BRBV is vectored via the tick, which is widely distributed throughout the central, eastern, and southern United States. Serosurveillance studies in Missouri and North Carolina identified BRBV-neutralizing antibodies in approximately 0.

Capacitive Biosensor for Rapid Detection of Avian (H5N1) Influenza and in Aerosols.

Airborne transmission via aerosols is a dominant route for the transmission of respiratory pathogens, including avian H5N1 influenza A virus and bacteria. Rapid and direct detection of respiratory pathogen aerosols has been a long-standing technical challenge. Herein, we develop a novel label-free capacitive biosensor using an interlocked Prussian blue (PB)/graphene oxide (GO) network on a screen-printed carbon electrode (SPCE) for direct detection of avian H5N1 and .

Immunogenicity and efficacy of XBB.1.5 rS vaccine against the EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

Unlabelled: The continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates updating coronavirus disease 2019 (COVID-19) vaccines to match circulating strains. The immunogenicity and efficacy of these vaccines must be tested in pre-clinical animal models. In Syrian hamsters, we measured the humoral and cellular immune response after immunization with the nanoparticle recombinant Spike (S) protein-based COVID-19 vaccine (Novavax, Inc.

Mucosal immunization with ChAd-SARS-CoV-2-S prevents sequential transmission of SARS-CoV-2 to unvaccinated hamsters.

COVID-19 vaccines have successfully reduced severe disease and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, COVID-19 vaccines are variably effective in preventing transmission and symptomatic SARS-CoV-2 infection. Here, we evaluated the impact of mucosal or intramuscular vaccine immunization on airborne infection and transmission of SARS-CoV-2 in Syrian hamsters.

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer.

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition.

Immunogenicity and efficacy of XBB.1.5 rS vaccine against EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

The continued emergence of SARS-CoV-2 variants necessitates updating COVID-19 vaccines to match circulating strains. The immunogenicity and efficacy of these vaccines must be tested in pre-clinical animal models. In Syrian hamsters, we measured the humoral and cellular immune response after immunization with the nanoparticle recombinant Spike (S) protein-based COVID-19 vaccine (Novavax, Inc.

The Highly Conserved Stem-Loop II Motif Is Dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion.

The highly conserved stem-loop II motif is dispensable for SARS-CoV-2.

Unlabelled: The stem-loop II motif (s2m) is a RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion.

mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2.

Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune-evasion properties have arisen, which could jeopardize recently deployed vaccine- and antibody-based countermeasures.

Methods: Here, we evaluated in mice and hamsters the efficacy of a pre-clinical version of the Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs.

Myeloid Deletion of Nemo Causes Osteopetrosis in Mice Owing to Upregulation of Transcriptional Repressors.

The transcription factor NF-κB is central to numerous physiologic processes including bone development, and its activation is controlled by IKKγ (also called NEMO), the regulatory subunit of IKK complex. NEMO is X-linked, and mutations in this gene result in Incontinentia Pigmenti in human hemizygous females. In mice, global deficiency causes embryonic lethality.

Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation.

Increased Ser phosphorylation of tau microtubule-associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B2 receptor activation leads to selective Ser phosphorylation of tau in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in tau Ser phosphorylation reflects modification of the G protein-coupled BK B2 receptors themselves.