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The coronavirus disease 2019 (COVID-19) has had psychological impacts on healthcare workers. However, very few scales are available to specifically assess healthcare workers’ work-related stress and anxiety in response to viral epidemics. This study developed a new rating scale, the Stress and Anxiety to Viral Epidemics-9 (SAVE-9), and validated it among healthcare workers directly affected by COVID-19 in Korea. A total of 1,019 healthcare workers responded through anonymous questionnaires during April 20-30, 2020. Internal consistency of the SAVE-9 was measured through Cronbach’s alpha, and principal component analysis with varimax rotation was used to determine its component structure. It was also compared with the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 scales. Its most appropriate cut-off point was determined by conducting receiver operating characteristic analysis. The nine-item scale had satisfactory internal consistency (Cronbach’s α=0.795). It adopted a two-factor structure: (1) anxiety about viral epidemics and (2) work-related stress associated with viral epidemics (Bartlett’s test of sphericity, p < 0.001; Kaiser-Meyer-Olkin=0.85). Correlations between SAVE-9 and the other scales were statistically significant. The cut-off points of the SAVE-9 and its anxiety subcategory were 22 and 15, respectively, compared with a GAD-7 score of 5. The results suggest that the SAVE-9 is a useful, reliable, and valid tool to evaluate stress and anxiety responses in healthcare workers during viral epidemics.

Background The coronavirus disease 2019, or COVID-19, has had a major psychological impact on healthcare workers. However, very few scales are available to specifically assess work-related stress and anxiety in healthcare workers responding to a viral epidemic. This study developed a new assessment tool, the Stress and Anxiety to Viral Epidemics-9 (SAVE-9) and aimed to validate it among healthcare workers directly affected by COVID-19 in Korea. Methods A total of 1,019 healthcare workers responded through anonymous questionnaires during April 20–30, 2020. Exploratory factor analysis (EFA) was conducted to explore the construct validity, and the reliability was assessed using internal consistency measures of Cronbach's alpha coefficients. Receiver operating characteristic analysis was conducted to define the most appropriate cut-off point of SAVE-9 using the Generalized Anxiety Disorder-7 scale (GAD-7; ≥ 5). Second, Spearman's rank correlation coefficient was used to establish convergent validity for the SAVE-9 questionnaire with GAD-7 and the Patient Health Questionnaire-9. Results The nine-item scale had satisfactory internal consistency (Cronbach's α = 0.795). It adopted a two-factor structure: 1) anxiety regarding viral epidemics and 2) work-related stress associated with viral epidemics. A cut-off score of 22 for the SAVE-9 ascertained levels of stress and anxiety in response to a viral epidemic in healthcare workers that warranted clinical attention. Correlations between the SAVE-9 and the other scales were statistically significant ( P < 0.05). Conclusion The results suggest that the SAVE-9 is a useful, reliable, and valid tool to evaluate stress and anxiety responses in healthcare workers during viral epidemics.

Mapping protein interactions driving cancer Cancer is a genetic disease, and much cancer research is focused on identifying carcinogenic mutations and determining how they relate to disease progression. Three papers demonstrate how mutations are processed through networks of protein interactions to promote cancer (see the Perspective by Cheng and Jackson). Swaney et al . focus on head and neck cancer and identify cancer-enriched interactions, demonstrating how point mutant–dependent interactions of PIK3CA, a kinase frequently mutated in human cancers, are predictive of drug response. Kim et al . focus on breast cancer and identify two proteins functionally connected to the tumor-suppressor gene BRCA1 and two proteins that regulate PIK3CA. Zheng et al . developed a statistical model that identifies protein networks that are under mutation pressure across different cancer types, including a complex bringing together PIK3CA with actomyosin proteins. These papers provide a resource that will be helpful in interpreting cancer genomic data. —VV

Mapping protein interactions driving cancer Cancer is a genetic disease, and much cancer research is focused on identifying carcinogenic mutations and determining how they relate to disease progression. Three papers demonstrate how mutations are processed through networks of protein interactions to promote cancer (see the Perspective by Cheng and Jackson). Swaney et al . focus on head and neck cancer and identify cancer-enriched interactions, demonstrating how point mutant–dependent interactions of PIK3CA, a kinase frequently mutated in human cancers, are predictive of drug response. Kim et al . focus on breast cancer and identify two proteins functionally connected to the tumor-suppressor gene BRCA1 and two proteins that regulate PIK3CA. Zheng et al . developed a statistical model that identifies protein networks that are under mutation pressure across different cancer types, including a complex bringing together PIK3CA with actomyosin proteins. These papers provide a resource that will be helpful in interpreting cancer genomic data. —VV

This paper argues that the Korean plural marker -tul is best analyzed as a modifier to the nP projection, rather than as a head in the nominal extended projection such as Num or Div(ision), which a standard pluralizer (e.g., English -s) realizes. As a modifier, plural -tul bears the privative feature [plural], rather than the binary feature [±plural] reserved for a plural that realizes a head. Supporting evidence comes from the fact that the presence of -tul leads to an obligatorily plural reading, while a number-neutral reading obtains in its absence; -tul also shows no evidence of inflectional properties. Appearing as an adjunct to nP, -tul shows certain idiosyncrasies, such as irregularities in the range of nouns that it can occur with. Evidence against the common claim that -tul is associated with a definite reading is provided, which suggests that it cannot realize D or adjoin to DP. The major consequence of this paper is that the often observed non-co-occurrence of classifiers and plural markers is predicted only when the relation between the two morphemes is in syntactic complementary distribution, but may not be when the relation is in merely semantic complementary distribution.

During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure.

The yeast Nrd1 interacts with the C-terminal domain (CTD) of RNA polymerase II (RNApII) through its CTD-interacting domain (CID) and also associates with the nuclear exosome, thereby acting as both a transcription termination and RNA processing factor. Previously, we found that the Nrd1 CID is required to recruit the nuclear exosome to the Nrd1 complex, but it was not clear which exosome subunits were contacted. Here, we show that two nuclear exosome cofactors, Mpp6 and Trf4, directly and competitively interact with the Nrd1 CID and differentially regulate the association of Nrd1 with two catalytic subunits of the exosome. Importantly, Mpp6 promotes the processing of Nrd1-terminated transcripts preferentially by Dis3, whereas Trf4 leads to Rrp6-dependent processing. This suggests that Mpp6 and Trf4 may play a role in choosing a particular RNA processing route for Nrd1-terminated transcripts within the exosome by guiding the transcripts to the appropriate exonuclease.The Nrd1-Nab3-Sen1 complex terminates transcription of small non-coding RNAs by RNApII 2 (1-4). Nrd1 and Nab3 are sequence-specific RNA binding proteins, and Sen1 helicase (senataxin in humans) has an ATPase activity that directly dissociates RNApII from the templates (5). Nrd1 also recognizes the serine 5-phosphorylated (Ser(P)-5) CTD of RNApII using its CID (6). Because the Ser(P)-5 CTD is prevalent in the early stage of transcription, the Nrd1 CID-RNApII CTD interaction has been suggested to dictate a regional specificity of Nrd1-Nab3-Sen1-dependent transcription termination (7). Indeed, Nrd1havingtheCIDofRtt103thatrecognizestheSerine2-phosphorylated CTD becomes capable of triggering RNApII termination at regions where Nrd1-Nab3 binding sites and serine 2-phosphorylated CTD are co-localized, satisfyingly confirming this model (8).The RNAs generated via Nrd1-Nab3-Sen1-dependent termination are trimmed or degraded by the exosome, mediated by Nrd1 complex interactions with this 3Ј-5Ј exonuclease (9). Intriguingly, swapping or deletion of the Nrd1 CID reduced the interaction between Nrd1 and the exosome (8), indicating that the Nrd1 CID also plays an important role in coupling termination and RNA processing by recruiting the exosome.The nuclear exosome consists of the core exosome and a nuclear-specific subunit Rrp6 (PM/Scl100 in humans) that functions in RNA 3Ј-end processing using 3Ј-5Ј exoribonuclease activity (10 -13). The core exosome is a catalytically inactive barrel-shaped complex composed of nine subunits (Exo-9: RNase pleckstrin homology-like proteins (Rrp41/42/43/45/46 and Mtr3) and S1/KH domain proteins (Rrp4/40 and Csl4)) as well as Dis3 (also known as Rrp44), which is a 3Ј-5Ј exo/endonuclease. Located at the bottom of Exo-9, Dis3 trims or degrades the RNA substrates passed through the central pore of . In contrast, Rrp6 sits on top of the Exo-9 S1/KH ring above the central channel, and the RNAs traverse the S1/KH ring and enter into the active site of Rrp6 for degradation (15,16).The TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) complex is ...