General ADP-Ribosylation Mechanism Based on the Structure of ADP-Ribosyltransferase-Substrate Complexes.

ADP-ribosylation is a ubiquitous modification of proteins and other targets, such as nucleic acids, that regulates various cellular functions in all kingdoms of life. Furthermore, these ADP-ribosyltransferases (ARTs) modify a variety of substrates and atoms. It has been almost 60 years since ADP-ribosylation was discovered.

Optimal Limb Position for the Stress Ultrasound Evaluation of Elbow Valgus Laxity in Baseball Players.

Background: The optimal limb position during stress ultrasound (SUS) evaluation of elbow valgus laxity has not been standardized.

Purpose: To compare 2 elbow positions (at 90° and 30° of flexion) and report which position method better represents the increased valgus laxity characteristics of baseball players.

Study Design: Controlled laboratory study.

Impact of salvage chemotherapy after immune checkpoint inhibitor for recurrent or metastatic head and neck cancer.

Background: It is unclear witch regimen is optimal as salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) monotherapy for recurrent or metastatic head and neck cancer (RM-HNC).

Methods: This study enrolled 109 patients. Overall survival (OS) and progression-free survival 2 (PFS2) were compared between patients stratified by SCT regimen.

Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.

Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan.

Release from persistent T cell receptor engagement and blockade of aryl hydrocarbon receptor activity enhance IL-6-dependent mouse follicular helper T-like cell differentiation in vitro.

Follicular helper T (Tfh) cells are crucial for humoral immunity. Dysregulation of Tfh cell differentiation can cause infectious, allergic, and autoimmune diseases. To elucidate the molecular mechanisms underlying Tfh cell differentiation, we attempted to establish an in vitro mouse model of Tfh cell differentiation in the absence of other cell types.

Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile.

Some bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically important bacterium with such a system is Clostridioides difficile (formerly Clostridium). The CDTa and CDTb proteins from its system represent important therapeutic targets.

Impact of tumor burden on survival in patients with recurrent or metastatic head and neck cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have become the standard treatment for recurrent or metastatic head and neck cancer (RM-HNC). However, many patients fail to benefit from the treatment. Previous studies have revealed that tumor burden predicts the efficacy of ICIs, but this association remains unclear for RM-HNC.

Germacrane sesquiterpenes from leaves of Eupatorium chinense inhibit protein tyrosine phosphatase.

Three new germacrane-type sesquiterpene lactones (1-3) were isolated alongside seven known related congeners (4-10) from the leaves of Eupatorium chinense L. (Compositae). The planar structures of 1-3 were elucidated by their spectroscopic data, including 1D and 2D NMR spectra.

Novel Prognostic Score for recurrent or metastatic head and neck cancer patients treated with Nivolumab.

Although several prognostic factors in nivolumab therapy have been reported in recurrent or metastatic head and neck cancer (RM-HNC) patients, these factors remain controversial. Here, we conducted a multicenter retrospective cohort study to investigate the impact of clinico-hematological factors on survival in RM-HNC patients treated with nivolumab. We reviewed 126 RM-HNC patients from seven institutes.

Retrograde Transgene Expression via Neuron-Specific Lentiviral Vector Depends on Both Species and Input Projections.

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system.

Long-term efficacy of weekly paclitaxel therapy in unresectable primary squamous cell carcinoma of the thyroid.

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare disease with a poor prognosis. Because of its rarity, there is no established therapeutic regimen in unresectable cases. We report a case of PSCCT treated with weekly paclitaxel (wPTX) for more than 2 years.

Preparation of Clostridium perfringens binary iota-toxin pore complex for structural analysis using cryo-EM.

Iota toxin, a type of A-B toxin produced by Clostridium perfringens, comprises an enzymatic component (Ia) and a membrane-binding component (Ib). The translocation of Ia to the target cell via the pore formed by Ib allows it to function as an ADP-ribosyltransferase that inhibits actin polymerization in the host cell. The structure of Ia-bound Ib-pore has been determined using cryo-electron microscopy (cryo-EM), thereby elucidating the mechanism of the initial Ia translocation; however, open questions regarding Ia translocation still exist.

Common Mechanism for Target Specificity of Protein- and DNA-Targeting ADP-Ribosyltransferases.

Many bacterial pathogens utilize ADP-ribosyltransferases (ARTs) as virulence factors. The critical aspect of ARTs is their target specificity. Each individual ART modifies a specific residue of its substrates, which could be proteins, DNA, or antibiotics.

A myelin sheath protein forming its lattice.

The formation of a mature, multilayered myelin sheath requires the compaction of lipid bilayers, but the molecular mechanism by which these bilayers condense is an open question. In this issue, Ruskamo find that peripheral myelin protein P2 forms an ordered three-dimensional lattice within model membranes using polar lipid liposomes. These data will help to understand the assembly, function, and structure of the myelin sheath.

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan.

Background: Globally, the use of single DTaP-IPV/Hib vaccines that combine DTaP-IPV and Hib is widespread, but in Japan vaccination is usually concomitant at separate sites. The immunogenicity and safety of a primary vaccination series and booster of a combined pentavalent DTaP-IPV/Hib vaccine were evaluated and compared to separate administration of DTaP-IPV and Hib in Japanese infants.

Methods: Healthy Japanese infants were administered DTaP-IPV/Hib (Group A: N = 207) or DTaP-IPV + Hib (Group B: N = 207) by the subcutaneous (SC) or DTaP-IPV/Hib by the intramuscular (IM) route (Group C: N = 10).

Cryo-EM structures reveal translocational unfolding in the clostridial binary iota toxin complex.

The iota toxin produced by Clostridium perfringens type E is a binary toxin comprising two independent polypeptides: Ia, an ADP-ribosyltransferase, and Ib, which is involved in cell binding and translocation of Ia across the cell membrane. Here we report cryo-EM structures of the translocation channel Ib-pore and its complex with Ia. The high-resolution Ib-pore structure demonstrates a similar structural framework to that of the catalytic ϕ-clamp of the anthrax protective antigen pore.

A note on retrograde gene transfer efficiency and inflammatory response of lentiviral vectors pseudotyped with FuG-E vs. FuG-B2 glycoproteins.

Pseudotyped lentiviral vectors give access to pathway-selective gene manipulation via retrograde transfer. Two types of such lentiviral vectors have been developed. One is the so-called NeuRet vector pseudotyped with fusion glycoprotein type E, which preferentially transduces neurons.

Substrate N atom recognition mechanism in pierisin family DNA-targeting, guanine-specific ADP-ribosyltransferase ScARP.

ScARP from the bacterium belongs to the pierisin family of DNA-targeting ADP-ribosyltransferases (ARTs). These enzymes ADP-ribosylate the N amino groups of guanine residues in DNA to yield N-(ADP-ribos-1-yl)-2'-deoxyguanosine. Although the structures of pierisin-1 and Scabin were revealed recently, the substrate recognition mechanisms remain poorly understood because of the lack of a substrate-binding structure.

Involvement of the Arg566 residue of Aeromonas sobria serine protease in substrate specificity.

Aeromonas sobria serine protease (ASP) is an extracellular serine protease secreted by the organism. Here, we identified the amino acid residue of ASP that contributes to substrate specificity by using both synthetic peptides and biological protein components. The results showed that the arginine residue at position 566 (Arg-566) of ASP, which is located in the extra occluding region of ASP close to an entrance of the catalytic cavity, is involved in the substrate specificity.

The use of an optimized chimeric envelope glycoprotein enhances the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain.

Lentiviral vectors have been used not only for various basic research experiments, but also for a wide range of gene therapy trials in animal models. The development of a pseudotyped lentiviral vector with the property of retrograde infection allows us to introduce foreign genes into neurons that are localized in regions innervating the site of vector injection. Here, we report the efficiency of retrograde gene transfer of a recently developed FuG-E pseudotyped lentiviral vector in the primate brain by comparing its transduction pattern with that of the parental FuG-C pseudotyped vector.

Crystal structure and structure-based mutagenesis of actin-specific ADP-ribosylating toxin CPILE-a as novel enterotoxin.

Unusual outbreaks of food poisoning in Japan were reported in which Clostridium perfringens was strongly suspected to be the cause based on epidemiological information and fingerprinting of isolates. The isolated strains lack the typical C. perfringens enterotoxin (CPE) but secrete a new enterotoxin consisting of two components: C.