Cryo-EM structure of orf virus scaffolding protein orfv075.

Capsid-like poxvirus scaffold proteins self-assemble into semi-regular lattice that govern the formation of spherical immature virus particles. The scaffolding is a critical step in virus morphogenesis as exemplified by the drug rifampicin that impairs the recruitment of scaffold onto the viral membrane in vaccinia virus (VACV). Here we report cryo-electron microscopy structure of scaffolding protein Orfv075 of orf virus (ORFV) that causes smallpox-like diseases in sheep, goats and occasionally humans via zoonotic infection. We demonstrate that the regions that are involved in intertrimeric interactions for scaffold assembly are largely conserved in comparison to its VACV orthologue protein D13 whose intermediate assembly structures have been previously characterized. By contrast, less conserved regions are located away from these interfaces, indicating both viruses share similar assembly mechanisms. We also show that the phenylalanine-rich binding site of rifampicin in D13 is conserved in Orfv075, and molecular docking simulation confirms similar binding modes. Our study provides structural basis of scaffolding protein as a target for anti-poxvirus treatment across wide range of poxvirus genera.

Recent Progress of Advanced Functional Separators in Lithium Metal Batteries.

As a representative in the post-lithium-ion batteries (LIBs) landscape, lithium metal batteries (LMBs) exhibit high-energy densities but suffer from low coulombic efficiencies and short cycling lifetimes due to dendrite formation and complex side reactions. Separator modification holds the most promise in overcoming these challenges because it utilizes the original elements of LMBs. In this review, separators designed to address critical issues in LMBs that are fatal to their destiny according to the target electrodes are focused on. On the lithium anode side, functional separators reduce dendrite propagation with a conductive lithiophilic layer and a uniform Li-ion channel or form a stable solid electrolyte interphase layer through the continuous release of active agents. The classification of functional separators solving the degradation stemming from the cathodes, which has often been overlooked, is summarized. Structural deterioration and the resulting leakage from cathode materials are suppressed by acidic impurity scavenging, transition metal ion capture, and polysulfide shuttle effect inhibition from functional separators. Furthermore, flame-retardant separators for preventing LMB safety issues and multifunctional separators are discussed. Further expansion of functional separators can be effectively utilized in other types of batteries, indicating that intensive and extensive research on functional separators is expected to continue in LIBs.

Photosystem II monomeric antenna CP26 plays a key role in nonphotochemical quenching in Chlamydomonas.

Thermal dissipation of excess excitation energy, called nonphotochemical quenching (NPQ), is 1 of the main photoprotective mechanisms in oxygenic photosynthetic organisms. Here, we investigated the function of the monomeric photosystem II (PSII) antenna protein CP26 in photoprotection and light harvesting in Chlamydomonas reinhardtii, a model organism for green algae. We used CRISPR/Cas9 genome editing and complementation to generate cp26 knockout mutants (named k6#) that did not negatively affect CP29 accumulation, which differed from previous cp26 mutants, allowing us to compare mutants specifically deprived of CP26, CP29, or both. The absence of CP26 partially affected PSII activity, causing reduced growth at low or medium light but not at high irradiances. However, the main phenotype observed in k6# mutants was a more than 70% reduction of NPQ compared to the wild type (Wt). This phenotype was fully rescued by genetic complementation and complemented strains accumulating different levels of CP26, demonstrating that ∼50% of CP26 content, compared to the Wt, was sufficient to restore the NPQ capacity. Our findings demonstrate a pivotal role for CP26 in NPQ induction, while CP29 is crucial for PSII activity. The genetic engineering of these 2 proteins could be a promising strategy to regulate the photosynthetic efficiency of microalgae under different light regimes.

Orbital-Selective Mott Transition Effects and Nontrivial Topology of Iron Chalcogenide.

The iron-based superconductor FeSe_{1-x}Te_{x} has recently gained significant attention as a host of two distinct physical phenomena: (i) Majorana zero modes that can serve as potential topologically protected qubits, and (ii) a realization of the orbital-selective Mott transition. In this Letter, we connect these two phenomena and provide new insights into the interplay between strong electronic correlations and nontrivial topology in FeSe_{1-x}Te_{x}. Using linearized quasiparticle self-consistent GW plus dynamical mean-field theory, we show that the topologically protected Dirac surface state has substantial Fe(d_{xy}) character. The proximity to the orbital-selective Mott transition plays a dual role: it facilitates the appearance of the topological surface state by bringing the Dirac cone close to the chemical potential but destroys the Z_{2} topological superconductivity when the system is too close to the orbital-selective Mott phase. We derive a reduced effective Hamiltonian that describes the topological band. Its parameters capture all the chemical trends found in the first principles calculation. Our findings provide a framework for further study of the interplay between strong electronic correlations and nontrivial topology in other iron-based superconductors.

Utilizing systems genetics to enhance understanding into molecular targets of skin cancer.

Despite progress made with immune checkpoint inhibitors and targeted therapies, skin cancer remains a significant public health concern in the United States. The intricacies of the disease, encompassing genetics, immune responses, and external factors, call for a comprehensive approach. Techniques in systems genetics, including transcriptional correlation analysis, functional pathway enrichment analysis, and protein-protein interaction network analysis, prove valuable in deciphering intricate molecular mechanisms and identifying potential diagnostic and therapeutic targets for skin cancer. Recent studies demonstrate the efficacy of these techniques in uncovering molecular processes and pinpointing diagnostic markers for various skin cancer types, highlighting the potential of systems genetics in advancing innovative therapies. While certain limitations exist, such as generalizability and contextualization of external factors, the ongoing progress in AI technologies provides hope in overcoming these challenges. By providing protocols and a practical example involving Braf, we aim to inspire early-career experimental dermatologists to adopt these tools and seamlessly integrate these techniques into their skin cancer research, positioning them at the forefront of innovative approaches in combating this devastating disease.

Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals.

Long-lived "memory-like" NK cells have been identified in individuals infected by human cytomegalovirus (HCMV), but little is known about how the memory-like NK cell pool is formed. Here, we have shown that HCMV-infected individuals have several distinct subsets of memory-like NK cells that are often deficient for multiple transcription factors and signaling proteins, including tyrosine kinase SYK, for which the reduced expression was stable over time and correlated with epigenetic modification of the gene promoter. Deficient expression of these proteins was largely confined to the recently discovered FcRγ-deficient NK cells that display enhanced antibody-dependent functional activity. Importantly, FcRγ-deficient NK cells exhibited robust preferential expansion in response to virus-infected cells (both HCMV and influenza) in an antibody-dependent manner. These findings suggest that the memory-like NK cell pool is shaped and maintained by a mechanism that involves both epigenetic modification of gene expression and antibody-dependent expansion.

A Recombinant Ig Fragment (IgCw-γεκ) Comprising the Cγ1-Cε2-4 and Cκ Domains Is an Alternative Reagent to Human IgE.

Human IgE is useful for immunological assays, such as sensitization of FcεRI-positive cells and IgE measurement. In this study, we report the development of a recombinant Ig fragment, designated IgCw-γεκ, as an alternative reagent to human IgE. IgCw-γεκ (∼130 kDa) comprises two hybrid constant H chain regions (Cγ1-Cε2-4, each ∼53 kDa) and two constant κ L chains (Cκ, each ∼12 kDa) and lacks a V domain. The presence of Cγ1 instead of Cε1 within the H chain increased the production yield and facilitated assembly of the H and L chains. IgCw-γεκ was produced in cultured human embryonic kidney 293F cells, with a yield of ∼27 mg/l. IgCw-γεκ bound to human FcεRIαRs expressed on the surface of rat basophilic leukemia-2H3 cells. A ß-hexosaminidase release assay revealed that the biological activity of IgCw-γεκ was comparable with that of IgE. The IgE concentration measured using IgCw-γεκ as a standard was similar to that measured using IgE as a standard. These results suggest that the IgCw-γεκ molecule retains the basic characteristics of IgE, but does not cross-react with Ags, making it an alternative to the IgE isotype references used in a variety of immunological assays.

Predictive coding across the left fronto-temporal hierarchy during language comprehension.

We used magnetoencephalography (MEG) and event-related potentials (ERPs) to track the time-course and localization of evoked activity produced by expected, unexpected plausible, and implausible words during incremental language comprehension. We suggest that the full pattern of results can be explained within a hierarchical predictive coding framework in which increased evoked activity reflects the activation of residual information that was not already represented at a given level of the fronto-temporal hierarchy ("error" activity). Between 300 and 500 ms, the three conditions produced progressively larger responses within left temporal cortex (lexico-semantic prediction error), whereas implausible inputs produced a selectively enhanced response within inferior frontal cortex (prediction error at the level of the event model). Between 600 and 1,000 ms, unexpected plausible words activated left inferior frontal and middle temporal cortices (feedback activity that produced top-down error), whereas highly implausible inputs activated left inferior frontal cortex, posterior fusiform (unsuppressed orthographic prediction error/reprocessing), and medial temporal cortex (possibly supporting new learning). Therefore, predictive coding may provide a unifying theory that links language comprehension to other domains of cognition.

Magnetite particles accelerate methanogenic degradation of highly concentrated acetic acid in anaerobic digestion process.

The anaerobic digestion (AD) process has become significant for its capability to convert organic wastewater into biogas, a valuable energy source. Excessive acetic acid accumulation in the anaerobic digester can inhibit methanogens, ultimately leading to the deterioration of process performance. Herein, the effect of magnetite particles (MP) as an enhancer on the methanogenic degradation of highly-concentrated acetate (6 g COD/L) was examined through long-term sequential AD batch tests. Bioreactors with (AM) and without (AO) MP were compared. AO experienced inhibition and its methane production rate (qm) converged to 0.45 L CH4/g VSS/d after 10 sequential batches (AO10, the 10th batch in a series of the sequential batch tests conducted using bioreactors without MP addition). In contrast, AM achieved 3-425% higher qm through the sequential batches, indicating that MP could counteract the inhibition caused by the highly-concentrated acetate. MP addition to inhibited bioreactors (AO10) successfully restored them, achieving qm of 1.53 L CH4/g VSS/d, 3.4 times increase from AO10 after 8 days lag time, validating its potential as a recovery strategy for inhibited digesters with acetate accumulation. AM exhibited higher microbial populations (1.8-3.8 times) and intracellular activity (9.3 times) compared to AO. MP enriched Methanosaeta, Peptoclostridium, Paraclostridium, OPB41, and genes related to direct interspecies electron transfer and acetate oxidation, potentially driving the improvement of qm through MP-mediated methanogenesis. These findings demonstrated the potential of MP supplementation as an effective strategy to accelerate acetate-utilizing methanogenesis and restore an inhibited anaerobic digester with high acetate accumulation.

Survey Validation for Measuring Perceptions of Work-Related Factors That Influence Career Paths of Men and Women in Academic Anesthesiology.

BACKGROUND: Women's underrepresentation in positions of leadership in medicine has been attributed to environmental, structural, motivational, and situational factors. The purpose of this study was to design and validate a survey instrument based on these constructs, using a sample of men and women anesthesiologists from 3 urban academic medical centers. METHODS: Following institutional review board review, survey domains were defined based on a literature review. Items were developed, and content validation was performed by external experts. Anesthesiologists at 3 academic institutions were invited to complete the anonymous survey. Validation measures were performed on the collected responses, including reliability, convergent, and discriminant validity. In addition, differences between men and women respondents were evaluated. RESULTS: Content validation by external experts yielded 38 items with 5-point Likert scales, defining 3 constructs: environmental (14 items), structural (13 items), and motivational (11 items) factors, with single-item measures on situational factors. Content validity indices used Cohen's Kappa coefficients, with 0.85 as the acceptance cutoff. Two hundred seventy-four anesthesiologists in 3 academic institutions received the online survey. One hundred fifteen responses were received (42% response rate), yielding 103 complete survey responses, of which 86 cases included gender. Cronbach's α reliability estimates for the environmental, structural, and motivational scale scores were .88, .84, and .64, respectively, after scale revision. Evidence of convergent (Pearson's r = 0.68; P < .001) and discriminant validity (Pearson's r = 0.017; P = .84) confirmed theoretical expectations. Gender group differences showed statistically significant differences in perceptions toward environmental but not toward structural and motivational factors. CONCLUSIONS: The iterative design and validation processes yielded a 3-scale survey instrument with parsimonious item sets. The preliminary evidence of construct validity and reliability fills a gap in the instrumentation literature for assessing gender issues in medicine. Findings were consistent with theoretical expectations. Women are more likely than men to experience challenges in the work environment for career advancement. No differences were found between men and women on perceived resources and overall motivation factors. Investigations should continue with larger and more diverse samples and medical specialties.