Herpes Simplex Virus 2 Virion Host Shutoff Endoribonuclease Activity Is Required To Disrupt Stress Granule Formation

We previously established that cells infected with herpes simplex virus 2 (HSV-2) are disrupted in their ability to form stress granules (SGs) in response to oxidative stress and that this disruption is mediated by virion host shutoff protein (vhs), a virion-associated endoribonuclease. Here, we test the requirement for vhs endoribonuclease activity in disruption of SG formation. We analyzed the ability of HSV-2 vhs carrying the point mutation D215N, which ablates its endoribonuclease activity, to disrupt SG formation in both transfected and infected cells. We present evidence that ablation of vhs endoribonuclease activity results in defects in vhs-mediated disruption of SG formation. Furthermore, we demonstrate that preformed SGs can be disassembled by HSV-2 infection in a manner that requires vhs endoribonuclease activity and that, befitting this ability to promote SG disassembly, vhs is able to localize to SGs. Together these data indicate that endoribonuclease activity must be maintained in order for vhs to disrupt SG formation. We propose a model whereby vhs-mediated destruction of SG mRNA promotes SG disassembly and may also prevent SG assembly. IMPORTANCE Stress granules (SGs) are transient cytoplasmic structures that form when a cell is exposed to stress. SGs are emerging as potential barriers to viral infection, necessitating a more thorough understanding of their basic biology. We identified virion host shutoff protein (vhs) as a herpes simplex virus 2 (HSV-2) protein capable of disrupting SG formation. As mRNA is a central component of SGs and the best-characterized activity of vhs is as an endoribonuclease specific for mRNA in vivo, we investigated the requirement for vhs endoribonuclease activity in disruption of SG formation. Our studies demonstrate that endoribonuclease activity is required for vhs to disrupt SG formation and, more specifically, that SG disassembly can be driven by vhs endoribonuclease activity. Notably, during the course of these studies we discovered that there is an ordered departure of SG components during their disassembly and, furthermore, that vhs itself has the capacity to localize to SGs

Ultrathin Magnesium-based Coating as an Efficient Oxygen Barrier for Superconducting Circuit Materials

Scaling up superconducting quantum circuits based on transmon qubits necessitates substantial enhancements in qubit coherence time. Among the materials considered for transmon qubits, tantalum (Ta) has emerged as a promising candidate, surpassing conventional counterparts in terms of coherence time. However, the presence of an amorphous surface Ta oxide layer introduces dielectric loss, ultimately placing a limit on the coherence time. In this study, we present a novel approach for suppressing the formation of tantalum oxide using an ultrathin magnesium (Mg) capping layer deposited on top of tantalum. Synchrotron-based X-ray photoelectron spectroscopy (XPS) studies demonstrate that oxide is confined to an extremely thin region directly beneath the Mg/Ta interface. Additionally, we demonstrate that the superconducting properties of thin Ta films are improved following the Mg capping, exhibiting sharper and higher-temperature transitions to superconductive and magnetically ordered states. Based on the experimental data and computational modeling, we establish an atomic-scale mechanistic understanding of the role of the capping layer in protecting Ta from oxidation. This work provides valuable insights into the formation mechanism and functionality of surface tantalum oxide, as well as a new materials design principle with the potential to reduce dielectric loss in superconducting quantum materials. Ultimately, our findings pave the way for the realization of large-scale, high-performance quantum computing systems

BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer

[Context]: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. [Objective]: To study whether BRAF V600E affected LNM-associated mortality in PTC. [Design, Setting, and Participants]: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. [Results]: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. [Conclusions]: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.This work was supported partly by the following funding at the individual participating centers: Polish National Center of Research and Development MILESTONE Project—molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant No. STRATEGMED2/267398/4/ NCBR/2015 (Poland, AC, BJ); Grants No. PID2019-105303RB-I00 (AEI from MICINN), GCB14142311CRES (AECC Foundation), and B2017/BMD-3724 TIRONET2-CM (Spain; PS and GR-E); Grant No. AZV 16-32665A and MH CZ-DRO (Institute of Endocrinology-EU, 00023761) (Czech Republic; BB, VS); NIH/ National Institute on Aging Grant No. 5R03AG042334-02 (LY); and grants from the Qingdao Science and Technology Project for People’s Livelihood No.13-1-3-58-nsh (China; FW) and the Innovative Platform Project of Qingdao No.12-1-2-15-jch (China; YW)

One-pot synthesis of diaryliodonium salts using toluenesulfonic acid - a fast entry to electron-rich diaryliodonium tosylates and triflates

A direct synthesis of symmetric and unsymmetric electron-rich diaryliodonium salts is described. The use of MCPBA and toluenesulfonic acid delivers diaryliodonium tosylates in high yields. An in situ anion exchange has also been developed, giving access to the corresponding triflate salts

The complete mitochondrial genome of Allium fistulosum L. (Amaryllidaceae)

Allium fistulosum L. (Linnaeus, Carolus, 1753) is an aromatic vegetable with health benefits and medicinal value. In this study, the complete mitochondrial genome of A. fistulosum was determined. Circular mitochondrial DNA (mtDNA) was 382,053 bp in size, encoded 44 genes, and contained 26 protein-coding genes (PCGs), 14 tRNAs, and four rRNAs. Phylogenetic analysis of amino acid sequences of the 26 PCGs revealed that the closest relationship was between A. fistulosum and Allium cepa. The high-quality mitochondrial genomic sequences of A. fistulosum presented in this study will serve as a useful resource for a range of genetic, functional, evolutionary, and comparative genomic studies on this species of the Amaryllidaceae family