Long noncoding RNA CHROMR regulates antiviral immunity in humans.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.

Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina.

Mutations in NMNAT1, a key enzyme involved in the synthesis of NAD+ in the nucleus, lead to an early onset severe inherited retinal degeneration (IRD). We aimed to understand the role of nuclear NAD+ in the retina and to identify the molecular mechanisms underlying NMNAT1-associated disease, using a mouse model that harbors the p.V9M mutation in Nmnat1 (Nmnat1V9M/V9M). We identified temporal transcriptional reprogramming in the retinas of Nmnat1V9M/V9M mice prior to retinal degeneration, which begins at 4 weeks of age, with no significant alterations in gene expression at 2 weeks of age and over 2600 differentially expressed genes by 3 weeks of age. Expression of the primary consumer of NAD+ in the nucleus, PARP1, an enzyme involved in DNA damage repair and transcriptional regulation, as well as 7 other PARP family enzymes, was elevated in the retinas of Nmnat1V9M/V9M. This was associated with elevated levels of DNA damage, PARP-mediated NAD+ consumption and migration of Iba1+/CD45+ microglia/macrophages to the subretinal space in the retinas of Nmnat1V9M/V9M mice. These findings suggest that photoreceptor cells are especially sensitive to perturbation of genome homeostasis, and that PARP-mediated cell death may play a role in other genetic forms of IRDs, and potentially other forms of neurodegeneration.

Evolutionary history and root trait coordination predict nutrient strategy in tropical legume trees.

Plants express diverse nutrient use and acquisition traits, but it is unclear how trait combinations at the species level are constrained by phylogeny, trait coordination, or trade-offs in resource investment. One trait - nitrogen (N) fixation - is assumed to correlate with other traits and used to define plant functional groups, despite potential confounding effects of phylogeny. We quantified growth, carbon metabolism, fixation rate, root phosphatase activity (RPA), mycorrhizal colonization, and leaf and root morphology/chemistry across 22 species of fixing and nonfixing tropical Fabaceae trees under common conditions. Belowground trait variation was high even among closely related species, and most traits displayed a phylogenetic signal, including N-fixation rate and nodule biomass. Across species, we observed strong positive correlations between physiological traits such as RPA and root respiration. RPA increased ~ fourfold per unit increase in fixation, supporting the debated hypothesis that N-fixers 'trade' N for phosphatases to enhance phosphorus acquisition. Specific root length and root N differed between functional groups, though for other traits, apparent differences became nonsignificant after accounting for phylogenetic nonindependence. We conclude that evolutionary history, trait coordination, and fixation ability contribute to nutrient trait expression at the species level, and recommend explicitly considering phylogeny in analyses of functional groupings.

Prescribed fire increases plant-pollinator network robustness to losses of rare native forbs.

Restoration efforts often focus on changing the composition and structure of invaded plant communities, with two implicit assumptions: (1) functional interactions with species of other trophic levels, such as pollinators, will reassemble automatically when native plant diversity is restored and (2) restored communities will be more resilient to future stressors. However, the impact of restoration activities on pollinator richness, plant-pollinator interaction network structure, and network robustness is incompletely understood. Leveraging a restoration chronosequence in Pacific Northwest prairies, we examined the effects of restoration-focused prescribed fire and native forb replanting on floral resources, pollinator visitation, and plant-pollinator network structure. We then simulated the effects of plant species loss/removal scenarios on secondary extinction cascades in the networks. Specifically, we explored three management-relevant plant loss scenarios (removal of an abundant exotic forb, removal of an abundant forb designated a noxious weed, and loss of the rarest native forb) and compared them to control scenarios. Pyrodiversity and proportion of area recently burned increased the abundance and diversity of floral resources, with concomitant increases in pollinator visitation and diversity. Pyrodiversity also decreased network connectance and nestedness, increased modularity, and buffered networks against secondary extinction cascades. Rare forbs contributed disproportionately to network robustness in less restored prairies, while removal of typical "problem" plants like exotic and noxious species had relatively small impacts on network robustness, particularly in prairies with a long history of restoration activities. Restoration actions aimed mainly at improving the diversity and abundance of pollinator-provisioning plants may also produce plant-pollinator networks with increased resilience to plant species losses.

A mild synthetic route to α-nitroso diaryl pyrroles.

A new synthetic method to access α-nitroso pyrroles is presented. This method utilises the nitrosonium salt NOBF4, enabling short reaction times (<10 minutes) and avoiding the harsh acidic conditions usually associated with pyrrole nitrosation. Application of this procedure to diarylated pyrroles yielded several novel nitroso-pyrroles. Modifications to the method, through exclusion of air and inclusion of a mild base, allowed for the nitrosation of pyrroles bearing aryl groups substituted with electron-donating groups. Attempts to nitrosylate pyrroles bearing alkyl substituents resulted in the formation of a dimeric material composed of a pyrrolic unit and a 2-hydroxyimino-protected 1,5-dihydro-2H-pyrrol-2-one.

Distinguishing Surface and Bulk Reactivity: Concentration-Dependent Kinetics of Iodide Oxidation by Ozone in Microdroplets.

Iodine oxidation reactions play an important role in environmental, biological, and industrial contexts. The multiphase reaction between aqueous iodide and ozone is of particular interest due to its prevalence in the marine atmosphere and unique reactivity at the air-water interface. Here, we explore the concentration dependence of the I- + O3 reaction in levitated microdroplets under both acidic and basic conditions. To interpret the experimental kinetics, molecular simulations are used to benchmark a kinetic model, which enables insight into the reactivity of the interface, the nanometer-scale subsurface region, and the bulk interior of the droplet. For all experiments, a kinetic description of gas- and liquid-phase diffusion is critical to interpreting the results. We find that the surface dominates the iodide oxidation kinetics under concentrated and acidic conditions, with the reactive uptake coefficient approaching an upper limit of 10-2 at pH 3. In contrast, reactions in the subsurface dominate under more dilute and alkaline conditions, with inhibition of the surface reaction at pH 12 and an uptake coefficient that is 10× smaller. The origin of a changing surface mechanism with pH is explored and compared to previous ozone-dependent measurements.

Video consent significantly improves patient knowledge of general surgery procedures.

INTRODUCTION: Informed consent is essential in ensuring patients' understanding of their medical condition, treatment, and potential risks. The objective of this study was to investigate the impact of utilizing a video consent compared to standard consent for patient knowledge and satisfaction in selected general surgical procedures. METHODS AND PROCEDURES: We included 118 patients undergoing appendectomy, cholecystectomy, inguinal hernia repair, and fundoplication at two hospitals in Omaha, NE. Patients were randomized to either a standard consent or a video consent. Outcomes included a pretest and posttest objective knowledge assessment of their procedure, as well as a satisfaction survey which was completed immediately after consent and following discharge. Given the pre-post design, a linear mixed-effect model was estimated for both outcomes. A two-way interaction effect was of primary interest to assess whether pre-to-post change in the outcome differed between patients randomized to standard or video consent. RESULTS: Baseline characteristics were mostly similar between groups except for patient sex, p = 0.041. Both groups showed a statistically significant increase in knowledge from pretest to posttest (standard group: 0.25, 95% CI 0.01 to 0.51, p = 0.048; video group: 0.68, 95% CI 0.36 to 1.00, p < 0.001), with the video group showing significantly greater change (interaction p = 0.043) indicating that incorporating a video into the consent process resulted in a better improvement in patient's knowledge of the proposed procedure. Further, both groups showed a decrease in satisfaction post-discharge, but no statistically significant difference in the magnitude of decrease between the groups (interaction p = 0.309). CONCLUSION: Video consent lead to a significant improvement in a patient's knowledge of the proposed treatment. Although the patient satisfaction survey didn't show a significant difference, it did show a trend. We propose incorporating videos into the consent process for routine general surgical procedures.

Is it time for a paradigm shift? Inclusion of APOE on genetic dyslipidemia panels.

APOE codes for apolipoprotein E (ApoE), which plays an important role in lipid and lipoprotein metabolism and homeostasis of tissue lipid content. Several variants in APOE have been associated with inherited dyslipidemias, and a subsequent increased risk of developing premature coronary artery disease (CAD). However, these variants and their impact on risk can be thought of on a spectrum, with some being more monogenic in nature, and others contributing in a polygenic/multifactorial manner. Despite these known associations, there is often hesitancy around ordering APOE genetic testing due to the association with Alzheimer's disease. This paper aims to catalyze discussion around APOE testing and counseling strategies, highlight the nuances around this topic, and advocate for inclusion of APOE testing on dyslipidemia panels when an inherited dyslipidemia is suspected.

Mutant Nmnat1 leads to a retina-specific decrease of NAD+ accompanied by increased poly(ADP-ribose) in a mouse model of NMNAT1-associated retinal degeneration.

Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is required for nuclear nicotinamide adenine mononucleotide (NAD+) biosynthesis in all nucleated cells, and despite its functional ubiquity, mutations in this gene lead to an isolated retinal degeneration. The mechanisms underlying how mutant NMNAT1 causes disease are not well understood, nor is the reason why the pathology is confined to the retina. Using a mouse model of NMNAT1-associated retinal degeneration that harbors the p.Val9Met mutation, we tested the hypothesis that decreased function of mutant NMNAT1 has a greater effect on the levels of NAD+ in the retina than elsewhere in the body. Measurements by liquid chromatography with tandem mass spectrometry showed an early and sustained decrease of NAD+ in mutant retinas that was not observed in other tissues. To understand how consumers of nuclear NAD+ are affected by the reduced availability of NAD+ in mutant retinas, poly(ADP-ribose) polymerase (PARP) and nuclear sirtuin activity were evaluated. PARP activity was elevated during disease progression, as evidenced by overproduction of poly(ADP-ribose) (PAR) in photoreceptors, whereas histone deacetylation activity of nuclear sirtuins was not altered. We hypothesized that PARP could be activated because of elevated levels of oxidative stress; however, we did not observe oxidative DNA damage, lipid peroxidation, or a low glutathione to oxidized glutathione ratio. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining revealed that photoreceptors appear to ultimately die by apoptosis, although the low NAD+ levels and overproduction of PAR suggest that cell death may include aspects of the parthanatos cell death pathway.

Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque Regression.

[Figure: see text].