Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of in aged ferrets.

(DBV) is an emerging tick-borne virus that causes severe fever with thrombocytopenia syndrome (SFTS) in infected patients. Human SFTS symptoms progress from fever, fatigue, and muscle pain to the depletion of white blood cells and platelets with fatality rates up to 30%. The recent spread of its vector tick to over 20 states in the United States increases the potential for outbreaks of the SFTS beyond the East Asia.

SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.

With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility.

Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication.

Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound () and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3'-to-5' exoribonuclease (ExoN).

Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie Bandavirus in aged ferrets.

Dabie Bandavirus (DBV), previously known as Severe Fever with Thrombocytopenia Syndrome (SFTS) Virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (>4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation.

Glucosylceramide is essential for Heartland and Dabie bandavirus glycoprotein-induced membrane fusion.

Due to climate changes, there has been a large expansion of emerging tick-borne zoonotic viruses, including Heartland bandavirus (HRTV) and Dabie bandavirus (DBV). As etiologic agents of hemorrhagic fever with high fatality, HRTV and DBV have been recognized as dangerous viral pathogens that likely cause future wide epidemics. Despite serious health concerns, the mechanisms underlying viral infection are largely unknown.

MG1113, a specific anti-tissue factor pathway inhibitor antibody, rebalances the coagulation system and promotes hemostasis in hemophilia.

Background: Replacement therapy is the most common treatment for reduction of bleeding and control of episodic bleeding in individuals with hemophilia. Despite the proven effectiveness of factor replacement therapy, repeated intravenous administration is a heavy burden to individuals with hemophilia.

Objectives: To reduce the burden, therapeutic agents that can be subcutaneously administered need to be developed, and an anti-tissue factor pathway inhibitor (TFPI) antibody may be a suitable candidate for this purpose.

Performance of the Geriatric Depression Scale-15 with Older Adults Aged over 65 Years: An Updated Review 2000-2019.

Objectives: This up-to-date systematic review and meta-analysis aimed to examine the predictive validity of the Geriatric Depression Scale-15 (GDS-15) for screening depression in older adults aged over 65 years.

Methods: Electronic searches were performed on the MEDLINE, EMBASE, CINAHL, and PsycINFO database using the following keywords: depression, depressive disorder, major, geriatric depression scale, and geriatric depression scale short. The Quality Assessment of Diagnostic Accuracy Studies-2 was applied to assess the risk of bias in diagnostic studies.

How to Improve Patient Safety Literacy?

The aim of this comparative study involving pre- and post-tests was to analyze the effectiveness of patient safety educational materials developed for the Comprehensive Plans for Patient Safety in Korea (2018-2022), and to suggest how to improve patient safety literacy. A face-to-face survey interview comprising items related to general information and patient safety literacy was completed by 217 patients and their families who visited three general hospitals in Seoul and one general hospital in Gyeonggi-do for treatment between 25 October and 15 November 2019. In the interview, the patients were asked questions about whether the patient safety educational materials were "easy to understand," provided "help in safe hospitalization," and enabled patients to practice patient safety independently ("do it yourself").

Structural basis for effector protein recognition by the Dot/Icm Type IVB coupling protein complex.

The Legionella pneumophila Dot/Icm type IVB secretion system (T4BSS) is extremely versatile, translocating ~300 effector proteins into host cells. This specialized secretion system employs the Dot/Icm type IVB coupling protein (T4CP) complex, which includes IcmS, IcmW and LvgA, that are known to selectively assist the export of a subclass of effectors. Herein, the crystal structure of a four-subunit T4CP subcomplex bound to the effector protein VpdB reveals an interaction between LvgA and a linear motif in the C-terminus of VpdB.

Can patient and family education prevent medical errors? A descriptive study.

Background: This study aims to increase understanding of how patient and family education affects the prevention of medical errors, thereby providing basic data for developing educational contents.

Methods: This descriptive study surveyed patients, families, and Patient Safety Officers to investigate the relationship between educational contents and medical error prevention. The Chi-square test and ANOVA were used to derive the results of this study.

Evidence for binary Smc complexes lacking kite subunits in archaea.

SMC complexes play a central role in chromosome organization in all domains of life. The bacterial Smc-ScpAB complex is a three-subunit complex composed of Smc, ScpA and ScpB. ScpA bridges the two ATPase domains of the Smc homodimer, while ScpB, which belongs to the kite family of proteins, interacts with ScpA.

Author Correction: A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy.

Approaches to increase the activity of chimeric antigen receptor (CAR)-T cells against solid tumors may also increase the risk of toxicity and other side effects. To improve the safety of CAR-T-cell therapy, we computationally designed a chemically disruptable heterodimer (CDH) based on the binding of two human proteins. The CDH self-assembles, can be disrupted by a small-molecule drug and has a high-affinity protein interface with minimal amino acid deviation from wild-type human proteins.

Architecture of the type IV coupling protein complex of Legionella pneumophila.

Many bacteria, including Legionella pneumophila, rely on the type IV secretion system to translocate a repertoire of effector proteins into the hosts for their survival and growth. Type IV coupling protein (T4CP) is a hexameric ATPase that links translocating substrates to the transenvelope secretion conduit. Yet, how a large number of effector proteins are selectively recruited and processed by T4CPs remains enigmatic.

Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis.

Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. We show that Plk4 relocalizes from the inner Cep192 ring to the outer Cep152 ring as newly recruited Cep152 assembles around the Cep192-encircled daughter centriole. Crystal-structure analyses revealed that Cep192- and Cep152-derived peptides bind the cryptic polo box (CPB) of Plk4 in opposite orientations and in a mutually exclusive manner.

Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses.

Robust immune responses are essential for eliminating pathogens but must be metered to avoid prolonged immune activation and potential host damage. Upon recognition of microbial DNA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (STING) pathway and subsequent interferon (IFN) production. We report that the direct interaction between cGAS and the Beclin-1 autophagy protein not only suppresses cGAMP synthesis to halt IFN production upon double-stranded DNA (dsDNA) stimulation or herpes simplex virus-1 infection, but also enhances autophagy-mediated degradation of cytosolic pathogen DNA to prevent excessive cGAS activation and persistent immune stimulation.

Structural basis of intersubunit recognition in elongin BC-cullin 5-SOCS box ubiquitin-protein ligase complexes.

The cullin-RING ubiquitin ligases are multisubunit complexes that ubiquitinate various proteins. Six different cullins encoded by the human genome selectively pair with different adaptors and substrate receptors. It is presently poorly understood how cullin-2 (Cul2) and cullin-5 (Cul5) associate specifically with their adaptor elongin BC and a SOCS-box-containing substrate receptor.