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The genomes of RNA viruses encode the information required for replication in host cells both in their linear sequence and in complex higher-order structures. A subset of these RNA genome structures show clear sequence conservation, and have been extensively described for well-characterized viruses. However, the extent to which viral RNA genomes contain functional structural elements—unable to be detected by sequence alone—that nonetheless are critical to viral fitness is largely unknown. Here, we devise a structure-first experimental strategy and use it to identify 22 structure-similar motifs across the coding sequences of the RNA genomes for the four dengue virus serotypes. At least 10 of these motifs modulate viral fitness, revealing a significant unnoticed extent of RNA structure-mediated regulation within viral coding sequences. These viral RNA structures promote a compact global genome architecture, interact with proteins, and regulate the viral replication cycle. These motifs are also thus constrained at the levels of both RNA structure and protein sequence and are potential resistance-refractory targets for antivirals and live-attenuated vaccines. Structure-first identification of conserved RNA structure enables efficient discovery of pervasive RNA-mediated regulation in viral genomes and, likely, other cellular RNAs.

The genomes of RNA viruses encode the information required for replication in host cells in both their linear sequence and in complex higher-order structures. A subset of these complex functional RNA genome structures show clear sequence conservation. However, the extent to which viral RNA genomes contain conserved structural elements – that cannot be detected by sequence alone – that nonetheless are critical to viral fitness is largely unknown. Here, we take a structure-first approach to identify motifs conserved across the coding sequences of the RNA genomes for the four dengue virus (DENV) serotypes. We used SHAPE-MaP to identify 22 candidate motifs with conserved RNA structures, but no prior association with viral replication. At least ten of these motifs are important for viral fitness, revealing a significant unnoticed extent of RNA structure-mediated regulation within viral coding sequences. These conserved viral RNA structures promote a compact global genome architecture, interact with proteins, and regulate the viral replication cycle. These motifs are constrained at the levels of both RNA structure and protein sequence and are potential resistance-refractory targets for antivirals and live-attenuated vaccines. Structure-first identification of conserved RNA structure is poised to guide efficient discovery of RNA-mediated regulation in viral genomes and other cellular RNAs.

New Zealand apple exports must meet strict phytosanitary measures to eliminate codling moth (Cydia pomonella Linnaeus) (Lepidoptera: Tortricidae) larval infestation. This study was part of a program attempting the localized eradication of codling moth within an isolated cluster of seven orchards (391 ha). A conventional management program of insecticide sprays and pheromone mating disruption was supplemented with weekly releases of sterile moths for 1–6 yr. Our objective was to compare the recapture rate of sterile moths following their release by four methods, and the efficiency of each system. The methods were the following: a fixed-wing unmanned plane flying ~40–45 m high at 70 km/h, an unmanned hexacopter travelling 20 m high at 25 km/h, and manually from the ground via bicycles or motor vehicles. The different release methods were used in different years or weeks. Sterile male moths were recaptured in grids of pheromone traps positioned throughout each orchard. The highest recapture rate followed delivery by hexacopter, then bicycle, vehicle, and plane. There was a 17-fold difference in catches between releases by hexacopter and plane, and sixfold between vehicle and plane in the same season. Bicycle delivery had a 3.5-fold higher recapture rate than the plane in different years. The wind-borne horizontal drift of moths was investigated as a possible explanation for the disparity of recaptures between the two aircraft delivery systems. The methods in ascending order of time per hectare for delivery were the following: plane and vehicle, hexacopter, then bicycle. The advantages and disadvantages of each moth delivery method are discussed.

Synopsis Scientific culture and structure organize biological sciences in many ways. We make choices concerning the systems and questions we study. Our research then amplifies these choices into factors that influence the directions of future research by shaping our hypotheses, data analyses, interpretation, publication venues, and dissemination via other methods. But our choices are shaped by more than objective curiosity—we are influenced by cultural paradigms reinforced by societal upbringing and scientific indoctrination during training. This extends to the systems and data that we consider to be ethically obtainable or available for study, and who is considered qualified to do research, ask questions, and communicate about research. It is also influenced by the profitability of concepts like open-access—a system designed to improve equity, but which enacts gatekeeping in unintended but foreseeable ways. Creating truly integrative biology programs will require more than intentionally developing departments or institutes that allow overlapping expertise in two or more subfields of biology. Interdisciplinary work requires the expertise of large and diverse teams of scientists working together—this is impossible without an authentic commitment to addressing, not denying, racism when practiced by individuals, institutions, and cultural aspects of academic science. We have identified starting points for remedying how our field has discouraged and caused harm, but we acknowledge there is a long path forward. This path must be paved with field-wide solutions and institutional buy-in: our solutions must match the scale of the problem. Together, we can integrate—not reintegrate—the nuances of biology into our field.

Modification of the hepatitis C virus (HCV) positive-strand RNA genome by N6-methyladenosine (m(6)A) regulates the viral life cycle. This life cycle takes place solely in the cytoplasm, while m(6)A addition on cellular mRNA takes place in the nucleus. Thus, the mechanisms by which m(6)A is deposited on the viral RNA have been unclear. In this work, we find that m(6)A modification of HCV RNA by the m(6)A-methyltransferase proteins methyltransferase-like 3 and 14 (METTL3 and METTL14) is regulated by Wilms’ tumor 1-associating protein (WTAP). WTAP, a predominantly nuclear protein, is an essential member of the cellular mRNA m(6)A-methyltransferase complex and known to target METTL3 to mRNA. We found that HCV infection induces localization of WTAP to the cytoplasm. Importantly, we found that WTAP is required for both METTL3 interaction with HCV RNA and m(6)A modification across the viral RNA genome. Further, we found that WTAP, like METTL3 and METTL14, negatively regulates the production of infectious HCV virions, a process that we have previously shown is regulated by m(6)A. Excitingly, WTAP regulation of both HCV RNA m(6)A modification and virion production was independent of its ability to localize to the nucleus. Together, these results reveal that WTAP is critical for HCV RNA m(6)A modification by METTL3 and METTL14 in the cytoplasm. IMPORTANCE Positive-strand RNA viruses such as HCV represent a significant global health burden. Previous work has described that HCV RNA contains the RNA modification m(6)A and how this modification regulates viral infection. Yet, how this modification is targeted to HCV RNA has remained unclear due to the incompatibility of the nuclear cellular processes that drive m(6)A modification with the cytoplasmic HCV life cycle. In this study, we present evidence for how m(6)A modification is targeted to HCV RNA in the cytoplasm by a mechanism in which WTAP recruits the m(6)A-methyltransferase METTL3 to HCV RNA. This targeting strategy for m(6)A modification of cytoplasmic RNA viruses is likely relevant for other m(6)A-modified positive-strand RNA viruses with cytoplasmic life cycles such as enterovirus 71 and SARS-CoV-2 and provides an exciting new target for potential antiviral therapies.

Modification of the hepatitis C virus (HCV) positive-strand RNA genome by N6-methyladenosine (m6A) regulates the viral lifecycle. This lifecycle takes place solely in the cytoplasm, while m6A addition on cellular mRNA takes place in the nucleus. Thus, the mechanisms by which m6A is deposited on the viral RNA have been unclear. In this work, we find that m6A modification of HCV RNA by the m6A-methyltransferase proteins METTL3 and METTL14 is regulated by WTAP. WTAP, a predominantly nuclear protein, is an essential member of the cellular mRNA m6A-methyltransferase complex and known to target METTL3 to mRNA. We found that HCV infection induces localization of WTAP to the cytoplasm. Importantly, we found that WTAP is required for both METTL3 interaction with HCV RNA and for m6A modification across the viral RNA genome. Further, we found that WTAP, like METTL3 and METTL14, negatively regulates the production of infectious HCV virions, a process that we have previously shown is regulated by m6A. Excitingly, WTAP regulation of both HCV RNA m6A modification and virion production were independent of its ability to localize to the nucleus. Together, these results reveal that WTAP is critical for HCV RNA m6A modification by METTL3 and METTL14 in the cytoplasm.IMPORTANCEPositive-strand RNA viruses such as HCV represent a significant global health burden. Previous work has described how HCV RNA contains the RNA modification m6A and how this modification regulates viral infection. Yet, how this modification is targeted to HCV RNA has remained unclear due to the incompatibility of the nuclear cellular processes that drive m6A modification with the cytoplasmic HCV lifecycle. In this study, we present evidence for how m6A modification is targeted to HCV RNA in the cytoplasm by a mechanism in which WTAP recruits the m6A-methyltransferase METTL3 to HCV RNA. This targeting strategy for m6A modification of cytoplasmic RNA viruses is likely relevant for other m6A-modified positive-strand RNA viruses with cytoplasmic lifecycles such as enterovirus 71 and SARS-CoV-2 and provides an exciting new target for potential antiviral therapies.

Introduction Frailty has been recognised among people living with human immunodeficiency virus (HIV) and will become more prevalent in coming years given treatment success (Pathai et al J Gerontol A Biol Sci Med Sci 2014;69:833–842). Assessment of frailty and its common syndromes through comprehensive geriatric assessment (CGA) is routinely delivered by geriatricians and is likely to benefit these patients. We piloted a clinic to assess whether a future service would be beneficial for people living with HIV and frailty. Method 10 patients from the local HIV service, with suspected frailty, were referred to the Frailty Unit for assessment in May 2021. Each patient was assessed for frailty using the Fried model. They underwent CGA which included medication review, therapy assessment, cognitive assessment, using the Montreal Cognitive Assessment (MOCA), and review by a geriatrician. Results Seven people attended. Six underwent full assessment and one left prior to undergoing medical review. Patient demographics: all white males; mean age 53 years; mean years since HIV diagnosis 11.3; mean Nadir CD4 count 220.4; four with undetectable viral load and three low level viraemia. Four were classified as frail and three pre-frail. All were multimorbid (mean no. co-morbidities, 7.1). Significant medical issues were identified in four patients requiring further investigation and/or referral to other specialities. Polypharmacy was prevalent (mean no. medications 11.1) and medication adjustments were suggested for all patients. The mean MOCA score was 25.7, with two scoring less than 26 prompting memory service referral. Five patients had ongoing physiotherapy/occupational therapy needs. Conclusion This pilot demonstrated that a CGA approach to frail patients living with HIV identified significant multimorbidity, polypharmacy, cognitive impairment and therapy needs. This allowed for recommendations to be made to improve medical care, optimise function and improve quality of life. Consequently, a permanent HIV/Frailty service and referral pathway have been developed.

OBJECTIVES Implicit bias contributes to both health care disparities and professional limitations, and it exists among physicians. Prior literature has described physician weight bias (WB) toward patients, but little research has investigated interphysician WB. This study describes the prevalence of interphysician implicit WB and investigates the relationships between implicit, explicit, and professional biases. The authors hypothesized that the majority of physicians possess interphysician implicit WB and that the degree of implicit bias has a direct relationship with explicit and professional WB. METHODS In this cross-sectional study, a survey was used to measure interphysician implicit, explicit, and professional WB. It included adaptations of two previously validated measures (the Implicit Association Test and the Crandall Anti-fat Attitudes Questionnaire) and an investigator developed and tested Professional Weight Bias Scale. The survey was distributed electronically via medical society message boards, email lists, and social media groups. RESULTS A total of 620 physicians and medical students participated. Fifty-eight percent were female, ages ranged from 22 to 83 years (mean = 44 years), and body mass index (BMI) ranged from 16 to 59 (mean = 26). Descriptive analyses revealed that 87% had some degree of implicit interphysician antifat bias, with 31% and 34% categorized as moderate and severe, respectively. Correlation and multiple regression analyses revealed that male sex, increased age, and decreased BMI were related to increased implicit bias, controlling for all other factors. Furthermore, implicit, explicit, and professional bias all had significant, direct relationships with each other. CONCLUSIONS Our findings highlight the prevalence of interphysician implicit WB; the strong correlations between implicit, explicit, and professional WB; and the potential disparities faced by physicians with obesity. These results may be used to guide implicit bias training for a more inclusive medical workplace.

Recent discoveries have revealed that, during viral infection, the presence of the RNA modification N6-methyladenosine (m6A) on viral and cellular RNAs has profound impacts on infection outcome. Although m6A directly regulates many viral RNA processes, its effects on cellular RNAs and pathways during infection have only recently begun to be elucidated. Disentangling the effects of m6A on viral and host RNAs remains a challenge for the field. m6A has been found to regulate host responses such as viral RNA sensing, cytokine responses, and immune cell functions. We highlight recent findings describing how m6A modulates host responses to viral infection and discuss future directions that will lead to a synergistic understanding of the processes by which m6A regulates viral infection.

Today, in the United States, stressors abound. Familial, professional, religious, and social obligations, compounded by demanding digital interactions, can feel overwhelming to many. The average Am...

The RNA binding protein RIG-I is a key initiator of the antiviral innate immune response. The signaling that mediates the antiviral response downstream of RIG-I is transduced through the adaptor protein MAVS and results in the induction of type I and III interferons (IFN). This signal transduction occurs at endoplasmic reticulum (ER)-mitochondrial contact sites, to which RIG-I and other signaling proteins are recruited following their activation. RIG-I signaling is highly regulated to prevent aberrant activation of this pathway and dysregulated induction of IFN. Previously, we identified UFL1, the E3 ligase of the ubiquitin-like modifier conjugation system called ufmylation, UFL1, as one of the proteins recruited to membranes at ER-mitochondrial contact sites in response to RIG-I activation. Here, we show that UFL1, as well as the process of ufmylation, promote IFN induction in response to RIG-I activation. We find that following RNA virus infection, UFL1 is recruited to the membrane targeting protein 14-3-3ε, and that this complex is then recruited to activated RIG-I to promote downstream innate immune signaling. Importantly, we found that 14-3-3ε has an increase in UFM1-conjugation following RIG-I activation. Additionally, loss of cellular ufmylation prevents the interaction of 14-3-3ε with RIG-I, which abrogates the interaction of RIG-I with MAVS and thus downstream signal transduction that induces IFN. Our results define ufmylation as an integral regulatory component of the RIG-I signaling pathway and as a post-translational control for IFN induction.SignificanceThe viral RNA sensor RIG-I initiates the antiviral innate immune response by activating a signaling cascade that induces interferon. Activation of the RIG-I signaling pathway is highly regulated to quickly mount a protective immune response while preventing dysregulation that can lead to excessive inflammation or autoimmune disorders. Here, we characterize one such mechanism of regulation. We describe that UFL1, an E3 ligase for the ubiquitin-like modifier conjugation system called ufmylation, is important to promote RIG-I signaling. Using molecular approaches, we show that ufmylation promotes RIG-I interaction with the membrane targeting protein 14-3-3ε. As such, ufmylation positively regulates RIG-I recruitment to its signaling adaptor proteins MAVS for induction of interferon in response to RNA virus infection.

Adenovirus is a nuclear replicating DNA virus reliant on host RNA processing machinery. Processing and metabolism of cellular RNAs can be regulated by METTL3, which catalyzes the addition of N6-methyladenosine (m6A) to mRNAs. While m6A-modified adenoviral RNAs have been previously detected, the location and function of this mark within the infectious cycle is unknown. Since the complex adenovirus transcriptome includes overlapping spliced units that would impede accurate m6A mapping using short-read sequencing, here we profile m6A within the adenovirus transcriptome using a combination of meRIP-seq and direct RNA long-read sequencing to yield both nucleotide and transcript-resolved m6A detection. Although both early and late viral transcripts contain m6A, depletion of m6A writer METTL3 specifically impacts viral late transcripts by reducing their splicing efficiency. These data showcase a new technique for m6A discovery within individual transcripts at nucleotide resolution, and highlight the role of m6A in regulating splicing of a viral pathogen.

Background & Aims Coinfection with HDV causes rapid progression to liver cirrhosis and hepatic decompensation in patients with chronic hepatitis B. Factors that are associated with disease progression are poorly understood. In this study we aim to identify risk factors associated with disease progression and better characterise clinical differences and treatment response between HDV genotype 1 and 5. Methods In this retrospective study, all patients under our care between 2005 and 2016 with HBV/HDV coinfection (HBsAg+, anti-HDV antibodies positive) were analysed. Patients were excluded if follow-up was less than 6 months, if they had HCV and/or HIV coinfection or an acute HDV infection. Demographic data, stage of liver disease, development of liver complications and treatment response were recorded. Results One-hundred seven patients (mean age 36.0 years, 57% male) were followed for a median period of 4.4 years (range 0.6–28.1 years); 64% were of African origin and 17% were of European origin, with 28% of patients being cirrhotic at first visit; 43% patients had actively replicating HDV virus (anti-HDV-IgG+, anti-HDV-IgM+ or HDV RNA+) and 57% of patients were HDV exposed (anti-HDV-IgG+, HDV RNA-). Patients with actively replicating HDV more often developed liver complications than HDV-exposed patients (p = 0.002), but no differences in baseline characteristics were observed. Patients with HDV genotype 5 less often developed cirrhosis or hepatic decompensation compared to patients with HDV genotype 1. Twenty-four patients were treated with peg-IFN and post-treatment response was significantly better in patients infected with genotype 5 (10% GT1 vs. 64% GT5, p = 0.013). Conclusion Patients infected with HDV genotype 5 appear to have a better prognosis with fewer episodes of hepatic decompensation and better response to peg-IFN treatment than patients infected with HDV genotype 1. Lay summary Hepatitis delta is a virus that affects the liver. The virus is known to have different subtypes, called genotypes. With this research we discovered that hepatitis delta virus genotype 1 behaves differently than genotype 5 and causes faster development of liver disease. This is important for education of our patients and to determine how often we need to check our patients.

Induction of the antiviral innate immune response is highly regulated at the RNA level, particularly by RNA modifications. Recent discoveries have revealed how RNA modifications play key roles in cellular surveillance of nucleic acids and in controlling gene expression in response to viral infection. These modifications have emerged as being essential for a functional antiviral response and maintaining cellular homeostasis. In this review, we will highlight these and other discoveries that describe how the antiviral response is controlled by modifications to both viral and cellular RNA, focusing on how mRNA cap modifications, N6-methyladenosine, and RNA editing all contribute to coordinating an efficient response that properly controls viral infection.

Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably, CCAAT/enhancer binding proteins (C/EBPs). Here, we demonstrate the unexpected involvement of a posttranscriptional "epitranscriptomic" mRNA modification [N6-methyladenosine (m6A)] in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα. Prompted by the observation that C/EBPβ/δ-encoding transcripts contain m6A consensus sites, we show that Cebpd and Cebpb mRNAs are subject to m6A modification. Induction of C/EBPs is enhanced by an m6A methylase "writer" and suppressed by a demethylase "eraser." The only m6A "reader" found to be involved in this pathway was IGF2BP2 (IMP2), and IMP2 occupancy of Cebpd and Cebpb mRNA was enhanced by m6A modification. IMP2 facilitated IL-17-mediated Cebpd mRNA stabilization and promoted translation of C/EBPβ/δ in response to IL-17A, IL-17F, and TNFα. RNA sequencing revealed transcriptome-wide IL-17-induced transcripts that are IMP2 influenced, and RNA immunoprecipitation sequencing identified the subset of mRNAs that are directly occupied by IMP2, which included Cebpb and Cebpd Lipocalin-2 (Lcn2), a hallmark of autoimmune kidney injury, was strongly dependent on IL-17, IMP2, and C/EBPβ/δ. Imp2-/- mice were resistant to autoantibody-induced glomerulonephritis (AGN), showing impaired renal expression of C/EBPs and Lcn2 Moreover, IMP2 deletion initiated only after AGN onset ameliorated disease. Thus, posttranscriptional regulation of C/EBPs through m6A/IMP2 represents a previously unidentified paradigm of cytokine-driven autoimmune inflammation.

Signaling initiated by type I interferon (IFN) results in the induction of hundreds of IFN-stimulated genes (ISGs). The type I IFN response is important for antiviral restriction, but aberrant activation of this response can lead to inflammation and autoimmunity. Regulation of this response is incompletely understood. We previously reported that the mRNA modification m6A and its deposition enzymes, METTL3 and METTL14 (METTL3/14), promote the type I IFN response by directly modifying the mRNA of a subset of ISGs to enhance their translation. Here, we determined the role of the RNA demethylase FTO in the type I IFN response. FTO, which can remove either m6A or the cap-adjacent m6Am RNA modifications, has previously been associated with obesity and body mass index, type 2 diabetes, cardiovascular disease, and inflammation. We found that FTO suppresses the transcription of a distinct set of ISGs, including many known pro-inflammatory genes, and that this regulation is not through the actions of FTO on m6Am. Further, we found that depletion of FTO led to activation of STAT3, a transcription factor that mediates responses to various cytokines, but whose role in the type I IFN response is not well understood. This activation of STAT3 increased the expression of a subset of ISGs. Importantly, this increased ISG induction resulting from FTO depletion was partially ablated by depletion of STAT3. Together, these results reveal that FTO negatively regulates STAT3-mediated signaling that induces proinflammatory ISGs during the IFN response, highlighting an important role for FTO in suppression of inflammatory genes.

This study analyzes the correlation between required years of Bible courses and academic rigor at select private Christian schools. These findings, derived from the author’s doctoral research, show a threshold of under 4 years of required Bible courses for optimal academic perception among these schools. This threshold correlates with a medium to strong effect size and demonstrates a tension between academic strength and integration of faith and learning. This finding calls attention to Christian schools’ need to examine their priorities as both Christian and academic institutions. Theological and practical implications include extensions of the doctrine of sovereignty and curricular design.

In recent years, the RNA modification N6-methyladenosine (m6A) has been found to play a role in the life cycles of numerous viruses and also in the cellular response to viral infection. m6A has emerged as a regulator of many fundamental aspects of RNA biology. Here, we highlight recent advances in techniques for the study of m6A, as well as advances in our understanding of the cellular machinery that controls the addition, removal, recognition, and functions of m6A. We then summarize the many newly discovered roles of m6A during viral infection, including how it regulates innate and adaptive immune responses to infection. Overall, the goals of this review are to summarize the roles of m6A on both cellular and viral RNAs and to describe future directions for uncovering new functions of m6A during infection.

Innate immune detection of viral nucleic acids during viral infection activates a signaling cascade that induces type I and type III IFNs as well as other cytokines, to generate an antiviral response. This signaling is initiated by pattern recognition receptors, such as the RNA helicase retinoic acid-inducible gene I (RIG-I), that sense viral RNA. These sensors then interact with the adaptor protein mitochondrial antiviral signaling protein (MAVS), which recruits additional signaling proteins, including TNF receptor–associated factor 3 (TRAF3) and TANK-binding kinase 1 (TBK1), to form a signaling complex that activates IFN regulatory factor 3 (IRF3) for transcriptional induction of type I IFNs. Here, using several immunological and biochemical approaches in multiple human cell types, we show that the GTPase-trafficking protein RAB1B up-regulates RIG-I pathway signaling and thereby promotes IFN-β induction and the antiviral response. We observed that RAB1B overexpression increases RIG-I–mediated signaling to IFN-β and that RAB1B deletion reduces signaling of this pathway. Additionally, loss of RAB1B dampened the antiviral response, indicated by enhanced Zika virus infection of cells depleted of RAB1B. Importantly, we identified the mechanism of RAB1B action in the antiviral response, finding that it forms a protein complex with TRAF3 to facilitate the interaction of TRAF3 with mitochondrial antiviral signaling protein. We conclude that RAB1B regulates TRAF3 and promotes the formation of innate immune signaling complexes in response to nucleic acid sensing during RNA virus infection.

This research brief provides one of the first examinations of the impact of COVID-19 mortality on immigrant communities in the United States. In the absence of national data, we examine COVID-19 deaths in Minnesota, historically one of the major U.S. refugee destinations, using individual-level death certificates obtained from the Minnesota Department of Health Office of Vital Records. Minnesota’s foreign-born crude COVID-19 death rates were similar to rates for the US-born, but COVID-19 death rates adjusted for age and gender were twice as high among the foreign-born. Among foreign-born Latinos, in particular, COVID-19 mortality was concentrated in relatively younger, prime working age men. Moreover, the place-based and temporal patterns of COVID-19 mortality were quite distinct, with the majority of US-born mortality concentrated in long-term care facilities and late in 2020, and foreign-born mortality occurring outside of residential institutions and earlier in the pandemic. The disparate impacts of COVID-19 for foreign-born Minnesotans demonstrate the need for targeted public health planning and intervention in immigrant communities. Supplementary Information The online version contains supplementary material available at 10.1007/s11113-021-09668-1.

As the only Australian of the trio, none had greater responsibility than the Chief of the General Staff (CGS), Vernon Sturdee. The foremost military position in Australia, the mantle of Sir Brudenell White, now fell on the shoulders of the 50-year-old Vernon Sturdee, who a year earlier had been a colonel and Director of Staff Duties at Army Headquarters. From 8 December 1941 onwards for about four months the Chiefs of Staff, Sturdee, Admiral Royle and Air Chief Marshal Burnett, were constantly directed to prepare appreciations for a worried government. After Blamey returned, Sturdee continued serving loyally as CGS until July 1942 when he was appointed head of the Australian military mission in Washington. On the morning of 15 February Sturdee telephoned the Prime Minister and urged him to order the convoys to be diverted to Australia. In late December 1941 the government directed Sturdee to send reinforcements to Malaya.

Across several decades there has been an unprecedented increase in immigration enforcement including detention and deportation. Immigration detention profoundly impacts those experiencing detention and their family members. An emerging area of research has found that immigrants experience a number of challenges which constrain and limit their decisions, choices, and options for security and integration in the United States due to social, political and structural determinants. These determinants lead to greater structural vulnerabilities among immigrants. The purpose of the current study was to illuminate the perceived vulnerabilities of detained noncitizen immigrants as they are raised and described while attending case hearings at the Bloomington, Minnesota immigration court. Through conducting a thematic analysis of notes derived from third party immigration court observers, three areas of perceived vulnerability were identified. These perceived vulnerabilities include 1) migration and motivations to migrate, 2) structural vulnerabilities (e.g., discrimination, financial insecurity, social ties and family support, stable or fixed residence, English language proficiency, health and mental health) in the US, and 3) challenges in navigating immigration detention. These findings demonstrate that noncitizen immigrants who are undergoing immigration detention are experiencing multiple intersecting vulnerabilities which profoundly impact their lives. Collaborative efforts across sectors are needed to work towards comprehensive immigration reforms including both short-term and long-term solutions to address pressing issues for noncitizens undergoing immigration detention.

Simple Summary Codling moth is a major pest of apples, and was accidentally introduced into New Zealand over 150 years ago. Many countries that New Zealand exports apples to do not have codling moth present and they want to keep it out. Therefore, apple growers must heavily control codling moth populations on their orchards. Currently, the main control tactics are insecticide applications and mating disruption, which uses the moth’s own sex pheromone to make the males unable to find females to mate. We aimed to supplement these tactics with the sterile insect technique (SIT) to further suppress the codling moth on orchards. SIT involves mass rearing and sterilizing codling moth and then releasing them onto orchards where they mate with wild insects resulting in no offspring. We released sterile insects onto seven orchards using unmanned aerial vehicles and ground releases. Six years of the program saw significant drops (90–99%) in wild moth populations. The SIT is an excellent tactic for reducing moth populations in export apple orchards. Abstract Codling moth was introduced into New Zealand, and remains a critical pest for the apple industry. Apples exported to some markets require strict phytosanitary measures to eliminate the risk of larval infestation. Mating disruption and insecticide applications are the principal means of suppression in New Zealand. We tested the potential for the sterile insect technique (SIT) to supplement these measures to achieve local eradication or suppression of this pest. SIT was trialed in an isolated group of six integrated fruit production (IFP) orchards and one organic orchard (total 391 ha), using sterilized insects imported from Canada, with release by unmanned aerial vehicle and from the ground. Eradication was not achieved across the region, but a very high level of codling moth suppression was achieved at individual orchards after the introduction of sterile moths in combination with mating disruption and larvicides. After six years of releases, catches of wild codling moths at three IFP orchards (224 ha) were 90–99% lower than in 2013–2014, the year before releases began. Catches at three other IFP orchards (129 ha) decreased by 67–97% from the year before releases began (2015–2016), from lower initial levels. At a certified organic orchard with a higher initial population under only organic larvicides and mating disruption, by 2019–2020, there was an 81% reduction in wild moths capture from 2016–2017, the year before releases began.

Recent discoveries have revealed that during viral infection the presence of the RNA modification N6-methyladenosine (m(6)A) on viral and cellular RNAs has profound impacts on infection outcome. While m(6)A directly regulates many viral RNA processes, its effects on cellular RNAs and pathways during infection have only recently begun to be elucidated. Disentangling the effects of m(6)A on viral and host RNAs remains a challenge for the field. m(6)A has been found to regulate host responses such as viral RNA sensing, cytokine responses, and immune cell functions. We highlight recent findings describing how m(6)A modulates host responses to viral infection and discuss future directions that will lead to a synergistic understanding of the processes by which m(6)A regulates viral infection.

RNA encoded by RNA viruses is highly regulated so that it can function in multiple roles during the viral life cycle. These roles include serving as the mRNA template for translation or the genetic material for replication as well as being packaged into progeny virions. RNA modifications provide an emerging regulatory dimension to the RNA of viruses. Modification of the viral RNA can increase the functional genomic capacity of the RNA viruses without the need to encode and translate additional genes. Further, RNA modifications can facilitate interactions with host or viral RNA-binding proteins that promote replication or can prevent interactions with antiviral RNA-binding proteins. The mechanisms by which RNA viruses facilitate modification of their RNA are diverse. In this review, we discuss some of these mechanisms, including exploring the unknown mechanism by which the RNA of viruses that replicate in the cytoplasm could acquire the RNA modification N6-methyladenosine.