Search

Introduction: The germline human leukocyte antigen (HLA) status has been found to be associated with immunotherapy outcomes in patients with NSCLC, but its correlation to immunotherapy-induced pneumonitis and prognostic impact in the Asian population remains largely unknown. Methods: We evaluated the HLA genotype of the germline and available tumor samples in 42 patients with programmed death-ligand 1 expression of 50% or higher undergoing pembrolizumab immunotherapy. The HLA allele expression was correlated with tumor response, disease survival, and the occurrence of pneumonitis. Results: It was observed that the germline HLA-C homozygosity and HLA-DRB1∗13 expression were related to a worse progression-free survival and treatment response. Importantly, all patients (7/7 patients) who developed pneumonitis in our cohort expressed the HLA-DPB1∗02 allele, and the incidence of pneumonitis was 31.8% (7/22 patients) in patients expressing this allele compared with 0% (0/20 patients) in those without this allele (p = 0.009). Investigation of the tumor samples from 15 patients revealed some degree of HLA loss in the HLA class I loci in 40% (6/15) of patients, and no significant difference in tumor mutation burden was found among patients with different treatment responses. Conclusion: Taken together, this study evaluated the impact of HLA status in both germline and tumor samples in patients with NSCLC with high programmed death-ligand 1 expression, and the high incidence of immunotherapy-induced pneumonitis in patients expressing the HLA-DPB1∗02 allele may suggest a routine HLA typing and closer monitoring in this patient subset.

Collagen-derived peptides have been gaining interest due to their potential to act as DPP-IV inhibitors, which are considered to have antidiabetic effects. This study focused on extracting type I collagen from discarded southern bluefin tuna skin, confirming its structure and properties, and then measuring the ability of its hydrolysates to act as DPP-IV inhibitors. First, type I collagen was purified from southern bluefin tuna skin, and the constituent subunit was found to contain the α3(I) chain. Next, enzymatic hydrolysates were prepared, and their DPP-IV inhibitory activity measurements were examined and compared. Collagenase hydrolysate showed the highest DPP-IV inhibitory activity (71.8 ± 0.3 %), and considering digestive degradation, collagenase-pepsin-trypsin hydrolysate was prepared and separated into fractions via anion exchange chromatography, cartridge column, and HPLC. Notably, the 70 % methanol eluted fraction separated via cartridge column was found to have an IC50 of 0.26 ± 0.01 mg/ml. Subsequently, a novel peptide GPSGGGYDV with the highest DPP-IV inhibitory activity (IC50 value 82±0.0 µM) was purified from this fraction and found to be a competitive inhibitor of DPP-IV. This is the first study to investigate the DPP-IV inhibitory potential of type I collagen hydrolysate from southern bluefin tuna.

Epigenomic annotations for the rat lag far behind those of human and mouse, despite the rat’s immense utility in pharmacological and behavioral studies and the need to understand their epigenetic mechanisms. We have designed a targeted-enrichment method followed by next-generation sequencing (Methyl-Seq) to identify DNA methylation (DNAm) signatures across the rat genome. The design reflected an attempt to create a more comprehensive investigation of the rat epigenome, as it included promoters, CpG islands, and island shores of all RefSeq genes. In this study, we implemented the rat Methyl-Seq platform and tested its ability to distinguish differentially methylated regions (DMRs) among three different tissue types, three distinct brain regions, and, in the hippocampus, between males and females. These comparisons yielded DNAm differences of differing magnitudes, many of which were independently validated by bisulfite pyrosequencing, including autosomal regions that were predicted to show the least degree of difference in DNAm between males and females. Quantitative reverse transcription PCR revealed that most genes associated with the DMRs showed tissue-, brain region-, and sex-specific differences in expression. In particular, we found evidence for sex-specific DNAm and expression differences at Tubb6, Lrrn2, Tex26, and Sox5l1, all of which play important roles in neurodevelopment and have been implicated in studies examining sex differences. Our results demonstrate the utility of the rat Methyl-Seq platform and suggest the presence of DNAm differences between the male and female hippocampus. The rat Methyl-Seq has the potential to provide epigenomic insights into pharmacological and behavioral studies performed in the rat.

Summary: Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p 15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114–285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

ObjectiveThe impact of chronic exposure to stress or glucocorticoids on psychiatric symptoms has been exemplified by cases of iatrogenic or endogenous hypercortisolism such as Cushing’s syndrome (CS). The amygdala plays an important role in mediating both stress and affective responses, and one of the key factors that link stress response and psychiatric symptoms is the corticotropin-releasing factor (CRF). Epigenetic changes, especially those occurring on CpG dinucleotides in DNA of glucocorticoid target genes in blood, have been previously implicated as potential predictors of glucocorticoid-related events in the central nervous system (CNS). In this study, we examined amygdala volume and mood symptoms in CS patients and aimed at evaluating whether these parameters were associated with blood DNA methylation of CRF.MethodsIn this cross-sectional study, 32 CS patients and 32 healthy controls matched for age, sex, and years of education underwent an MRI scan, a Beck Depression Inventory-II, and a State-Trait Anxiety Inventory. Genomic DNA extracted from total leukocytes were used for DNA methylation analysis of several CpG dinucleotides at the CRF promoter region.ResultsSignificant associations between CRF methylation vs. amygdala volume (CpG-1, P = 0.006) and depression scores (CpG-2, P = 0.01) were found. To assess whether the promoter CpG methylation has functional consequences, we examined RNA and DNA extracted from non-CS, postmortem amygdala tissues. A significant association between CpG methylation and gene expression (CpG-1, P = 0.004) was observed.ConclusionThese results demonstrate that methylation levels of the CRF promoter CpGs are associated with amygdala volume in CS and related mood symptoms. Methylation levels may also be associated with CRF expression. This finding supports the feasibility of using epigenetic patterns in blood as a surrogate for assessing GC-related pathologies in the brain.

Abstract Background Despite increased attention on treatment and prevention for suicidal adolescents, we know little about potential intervention targets. Episodic future thinking—the ability to imagine detailed, personal, and future‐oriented events—is a modifiable cognitive process that has been linked with suicidal ideation (SI) in adolescents. However, until now its modifiability has only been tested in adults. Method Adolescents (N = 176, ages 15–19; 71% SI) completed performance‐based measures of episodic future thinking (i.e., Experimental Recombination Paradigm) and memory immediately before and after an Episodic Specificity Induction (ESI). Results Adolescents produced a greater number of future episodic details after (vs. before) the ESI but showed no change in non‐episodic details (e.g., semantic information). Patterns of change in episodic future thinking were not moderated by SI history. Adolescents overall did not demonstrate change in past episodic detail counts after the ESI. However, there were select moderating effects of SI history on this effect. Conclusion Results show that episodic future thinking can change immediately following an episodic specificity induction among adolescents, regardless of whether they have previously experienced SI. This demonstration of within‐person change constitutes a foundational first step in examining malleability of episodic future thinking in adolescents and offers preliminary evidence of a cognitive mechanism that may be leveraged in service of reducing adolescents' SI.

Introduction: Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. Methods: Retrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. Results: Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7–12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6–15.0). Conclusions: The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.

Abstract Biomaterials are increasingly being designed and adapted to a wide range of structural applications, owing to their superior mechanical property-to-weight ratios, low cost, biodegradability, and CO2 capture. Bamboo, specifically, has an interesting anatomy with long tube-like vessels present in its microstructure, which can be exploited to improve its mechanical properties for structural applications. By filling these vessels with a resin, e.g. an applied external loading would be better distributed in the structure. One recent method of impregnating the bamboo is plastination, which was originally developed for preserving human remains. However, the original plastination process was found to be slow for bamboo impregnation application, while being also rather complicated/methodical for industrial adaptation. Accordingly, in this study, an improved plastination method was developed that is 40% faster and simpler than the original method. It also resulted in a 400% increase in open-vessel impregnation, as revealed by Micro-X-ray Computed Tomography imaging. The improved method involves three steps: acetone dehydration at room temperature, forced polymer impregnation with a single pressure drop to − 23 inHg, and polymer curing at 130 °C for 20 min. Bamboo plastinated using the new method was 60% stronger flexurally, while maintaining the same modulus of elasticity, as compared to the virgin bamboo. Most critically, it also maintained its biodegradability from cellulolytic enzymes after plastination, as measured by a respirometric technique. Fourier transform infrared-attenuated total reflection, and thermogravimetric analyses were conducted and showed that the plastinated bamboo’s functional groups were not altered significantly during the process, possibly explaining the biodegradability. Finally, using cone calorimetry, plastinated bamboo showed a faster ignition time, due to the addition of silicone, but a lower carbon monoxide yield. These results are deemed as a promising step forward for further improvement and application of this highly abundant natural fiber in engineering structures.

Abstract Oxygen is the sustenance of aerobic life and yet is highly toxic. In early life, antioxidants functioned solely to defend against toxic effects of reactive oxygen species (ROS). Later, as aerobic metabolisms evolved, ROS became essential for signalling. Thus, antioxidants are multifunctional and must detoxify, but also permit ROS signalling for vital cellular processes. Here we conduct metazoan-wide genomic assessments of three enzymatic antioxidant families that target the predominant ROS signaller, hydrogen peroxide: namely, monofunctional catalases (CAT), peroxiredoxins (PRX), and glutathione peroxidases (GPX). We reveal that the two most evolutionary ancient families, CAT and PRX, exhibit metazoan-wide conservation. In the basal animal lineage, sponges (phylum Porifera), we find all three antioxidant families, but with GPX least abundant. Poriferan CATs are distinct from bilaterian CATs, but the evolutionary divergence is small. Amongst PRXs, subfamily PRX6 is the most conserved, whilst subfamily AhpC-PRX1 is the largest; PRX4 is the only core member conserved from sponges to mammals and may represent the ancestral animal AhpC-PRX1. Conversely, for GPX, the most recent family to arise, only the cysteine-dependent subfamily GPX7 is conserved across metazoans, and common across Porifera. Our analyses illustrate that the fundamental functions of antioxidants have resulted in gene conservation throughout the animal kingdom.

Abstract Background Reactive derivatives of oxygen (reactive oxygen species; ROS) are essential in signalling networks of all aerobic life. Redox signalling, based on cascades of oxidation–reduction reactions, is an evolutionarily ancient mechanism that uses ROS to regulate an array of vital cellular processes. Hydrogen peroxide (H2O2) and superoxide anion (O2 •−) are employed as signalling molecules that alter the oxidation state of atoms, inhibiting or activating gene activity. Here, we conduct metazoan-wide comparative genomic assessments of the two enzyme families, superoxide dismutase (SOD) and NADPH oxidases (NOX), that generate H2O2 and/or O2 •− in animals. Results Using the genomes of 19 metazoan species representing 10 phyla, we expand significantly on previous surveys of these two ancient enzyme families. We find that the diversity and distribution of both the SOD and NOX enzyme families comprise some conserved members but also vary considerably across phyletic animal lineages. For example, there is substantial NOX gene loss in the ctenophore Mnemiopsis leidyi and divergent SOD isoforms in the bilaterians D. melanogaster and C. elegans. We focus particularly on the sponges (phylum Porifera), a sister group to all other metazoans, from which these enzymes have not previously been described. Within Porifera, we find a unique calcium-regulated NOX, the widespread radiation of an atypical member of CuZnSOD named Rsod, and a novel endoplasmic reticulum MnSOD that is prevalent across aquatic metazoans. Conclusions Considering the precise, spatiotemporal specificity of redox signalling, our findings highlight the value of expanding redox research across a greater diversity of organisms to better understand the functional roles of these ancient enzymes within a universally important signalling mechanism.

Exposure to stress or glucocorticoids (GCs) is associated with epigenetic and transcriptional changes in genes that either mediate or are targets of GC signalling. FKBP5 (FK506 binding protein 5) is one such gene that also plays a central role in negative feedback regulation of GC signalling and several stress-related psychiatric disorders. In this study, we sought to examine how the mouse Fkbp5 gene is regulated in a neuronal context and identify requisite factors that can mediate the epigenetic sequelae of excess GC exposure. Mice treated with GCs were used to establish the widespread changes in DNA methylation (DNAm) and expression of Fkbp5 across four brain regions. Then two cell lines were used to test the persistence, decay, and functional significance of GC-induced methylation changes near two GC response elements (GREs) in the fifth intron of Fkbp5. We also tested the involvement of DNMT1, cell proliferation, and MeCP2 in mediating the effect of GCs on DNAm and gene activation. DNAm changes at some CpGs persist while others decay, and reduced methylation states are associated with a more robust transcriptional response. Importantly, the ability to undergo GC-induced DNAm loss is tied to DNMT1 function during cell division. Further, GC-induced DNAm loss is associated with reduced binding of MeCP2 at intron 5 and a physical interaction between the fifth intron and promoter of Fkbp5. Our results highlight several key factors at the Fkbp5 locus that may have important implications for GC- or stress-exposure during early stages of neurodevelopment.

BackgroundDigital technology, the internet, and social media are increasingly investigated as promising means for monitoring symptoms and delivering mental health treatment. These apps and interventions have demonstrated preliminary acceptability and feasibility, but previous reports suggest that access to technology may still be limited among individuals with psychotic disorders relative to the general population. ObjectiveWe evaluated and compared access to and use of technology and social media in young adults with psychotic disorders (PD), young adults with clinical risk for psychosis (CR), and psychosis-free youths (PF). MethodsParticipants were recruited through a coordinated specialty care clinic dedicated toward early psychosis as well as ongoing studies. We surveyed 21 PD, 23 CR, and 15 PF participants regarding access to technology and use of social media, specifically Facebook and Twitter. Statistical analyses were conducted in R. Categorical variables were compared among groups using Fisher exact test, continuous variables were compared using 1-way ANOVA, and multiple linear regressions were used to evaluate for covariates. ResultsAccess to technology and social media were similar among PD, CR, and PF participants. Individuals with PD, but not CR, were less likely to post at a weekly or higher frequency compared to PF individuals. We found that decreased active social media posting was unique to psychotic disorders and did not occur with other psychiatric diagnoses or demographic variables. Additionally, variation in age, sex, and White versus non-White race did not affect posting frequency. ConclusionsFor young people with psychosis spectrum disorders, there appears to be no “technology gap” limiting the implementation of digital and mobile health interventions. Active posting to social media was reduced for individuals with psychosis, which may be related to negative symptoms or impairment in social functioning.

Abstract. Background. After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. Methods. A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. Results. Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P

This paper investigates the body’s role in grammar in argument sequences. Drawing from a database of public disputes on language use, we document the work of the palm-up gesture in action formation. Using conversation analysis and interactional linguistics, we show how this gesture is an interactional resource that indexes a particular epistemic stance—namely to cast the proposition being advanced as obvious. In this report, we focus on instances in which participants reach what we refer to as an ‘impasse’, at which point the palm up gesture becomes a resource for reasserting and pursuing a prior position, now laminated with an embodied claim of ‘obviousness’ that is grounded in the sequentiality of the interaction. As we show, the palm up gesture appears with and in response to a variety of syntactic and grammatical structures, and moreover can also function with no accompanying verbal utterance at all. This empirical observation challenges the assumption that a focus on grammar-in-interaction should begin with, or otherwise be examined in relation to, ‘standard’ verbal-only grammatical categories (e.g., imperative, declarative). We conclude by considering the gestural practice we focus on alongside verbal grammatical resources (specifically, particles) from typologically distinct languages, which we offer as a contribution to ongoing discussions regarding an embodied conceptualization of grammar—in this case, epistemicity.

Daily environmental oscillations that follow Earth’s rotation around the Sun set a metronome for life, under which all organisms have evolved. Entrainment to these cues allow organisms to rhythmically set the pace of their own endogenous biological clocks with which the timings of diverse cellular activities are coordinated. In recent years, our knowledge of biological rhythms has extended across all domains of life. This includes both free-living and symbiotic life forms. With the insurgence of metagenomic sequencing tools, the field of holobiont chronobiomics (encompassing chronobiology of host and its associated microbiota) has recently opened and gained significant traction. Here, we review current knowledge regarding free-living prokaryote rhythmic regulation before exploring active areas of research that consider the coordinated rhythmic regulatory activities of hosts and their symbionts as a single entity, i.e., holobiont, and even the extent to which rhythmicity influences virus–host interactions. We describe rhythmicity within non-photosynthetic bacteria, cyanobacteria, and archaea, before investigating the effect of light, and, thus, diel cycle, on viral life cycles and host–virus population dynamics in marine planktonic ecosystems along with their potential to influence host cyanobacterial circadian clocks. We then explore current evidence outlining coordinated rhythmic regulation within marine holobionts and the significance of this for holobiont health and adaptive fitness that, in turn, optimizes their success within their local environments. Finally, we assess the critical role of circadian regulation for holobiont innate immunity and metabolism within well-studied non-marine mammalian systems, and, thus, assess how this can guide us within understudied marine chronobiomics research.

Adult-based suicide theories have determined much of what we know about suicidal ideation. Here, we investigate the extent to which elements of the Integrated Motivational-Volitional (IMV) model generalize to adolescence, a period when rates of suicidal ideation increase dramatically. In a sample of community-based adolescents (n = 74), we tested whether defeat and entrapment related to suicidal ideation, and whether poor positive future thinking abilities exacerbated this association. Consistent with the IMV model, we found that defeat/entrapment was associated specifically with history of suicidal ideation, and not with history of suicide attempt. Defeat/entrapment was related to baseline suicidal ideation severity above and beyond depressive symptoms. While defeat/entrapment predicted future suicidal ideation controlling for history of ideation, it did not do so controlling for depressive symptoms. Counter to the IMV model, we initially found that the association between defeat/entrapment and suicidal ideation was strongest among adolescents with greater positive future thinking abilities. This was driven by the tendency to imagine more positive future events, particularly those that are less realistic and achievable. These findings call for a more nuanced understanding of defeat/entrapment and positive future thinking among adolescents, particularly in how they interact to predict recurrent suicidal ideation.

A major challenge in teaching is helping students integrate course concepts to understand the big picture of a field and apply those concepts in new situations. To address this challenge in a tutorial course about astrochemistry (taught by graduate students to chemistry undergraduates), we implemented a progressive writing assignment that culminated in a final presentation. In the progressive writing assignment, students chose an astrochemistry topic they found interesting to be the subject of three sequential papers, which became the basis for their presentations. The purpose of this assignment was to gradually introduce chemistry students to research areas in astronomy, which is by nature outside the general chemistry curriculum, while also providing students with regular feedback. Over the course of the assignment, students applied key themes in the course—significance of astrochemistry research, research methods, and chemistry in astronomical environments—separately to their chosen topics before explaining in the final presentation how these different aspects of astrochemistry work together. By incorporating stories and anaologies, rather than just facts, students gave presentations that were accessible to a novice audience. As a result, students explained broader impacts of astrochemistry research, rather than just focusing on results, and they entertained questions with answers that went beyond clarification of the material discussed.

Penelitian ini menggunakan pendekatan Balanced Scorecard, di mana hal ini dilakukan penelitian karena masih ada kinerja yang harus diketahui tidak hanya keuangan saja tetapi dari segi non keuangan juga. Penelitian ini bertujuan untuk menganalisis kinerja Rumah Sakir Daerah Madani dengan empat perspektif yaitu perspektif pelanggan, perspektif proses bisnis internal, perspektif pembelajaran dan pertumbuhan serta perspektif keuangan. Untuk perspektif pelanggan menggunakan 98 responden, perspektif proses bisnis internal dan perspektif pembelajaran dan pertumbuhan menggunakan 84 responden dan untuk perspektif keuangan menggunakan laporan keuangan Rumah Sakit periode 2015. Hasil pengukuran kinerja Rumah Sakit dengan menggunakan pendekatan Balanced Scorecard memperoleh hasil atau skor 0,7. Hasil ini menunjukkan bahwa kinerja Rumah Sakit dilihat dari pengukuran kinerja secara keseluruhan dikatakan Baik. Meskipun kinerja masing-masing perspektif belum maksimal, namun hal ini dapat menunjukkan kinerja yang baik bagi Rumah Sakit Daerah Madani. Penggunaan pengukuran balanced scorecard dalam organisasi dapat memberikan gambaran umum mengenai kinerja suatu organisasi yang lebih lengkap dan komprehensif.

The northern anchovy, Engraulis mordax, is a small planktivorous fish from the northeastern Pacific Ocean that is an important forage for fishes, birds, and marine mammals, and is also the target of a commercial fishery. Here, we assembled a complete 16,664 bp genome for the E. mordax mitochondrion, which encodes for 12S and 16S rRNAs, 22 tRNAs, 13 protein-coding genes, and a 1016 bp D-loop in the characteristic arrangement of Order Clupeiformes. Phylogenetic analysis confirmed the evolutionary relatedness of E. mordax to other fishes of Family Engraulidae within Order Clupeiformes, but also indicated non-monophyly for the herring family, Clupeidae.

The eastern oyster Crassostrea virginica is an ecologically and economically important species that is vulnerable to oil pollution. We assessed sublethal effects of soluble fractions of crude oil alone (WAF) and crude oil in combination with Corexit 9500 dispersant (CEWAF) on oysters at three life history stages. Veliger swimming, pediveliger settlement, and adult clearance rates were quantified after 24 h exposures to the contaminants. Veliger swimming speeds were not significantly impacted by 24 h exposures to WAF or CEWAF. A larger proportion of veligers were inactive following WAF and CEWAF exposure as compared to the control, but the effect was greater for pediveligers, and pediveliger settlement in the highest concentration CEWAF treatment decreased by 50% compared to controls. Thus, pediveligers may be particularly vulnerable to oil exposure. In the adults, we found significant clearance rates reductions that persisted 33 days after acute exposure to CEWAF. Knowledge of sublethal effects of oil and dispersant at multiple life history stages aids understanding of how this important species will respond to an oil spill.

Vaccination is the most practical means available for preventing influenza. Influenza vaccines require frequent updates to keep pace with antigenic drift of the virus, and the effectiveness, and sometimes the safety, of the vaccine can therefore vary from season to season. Three key populations that the World Health Organization recommends should be prioritized for influenza vaccination are pregnant women, children younger than 5 years of age and the elderly. This review discusses the burden of influenza and the safety and effectiveness profile of influenza vaccines recommended for these groups.

A single nucleotide polymorphism (SNP: rs1360780) in FKBP5 (FK506 Binding Protein 5) has been shown to interact with exposure to childhood adversity to promote loss of methylation and increase in gene expression in adults. We asked whether rs1360780 can influence FKBP5 intronic methylation in the context of exposure to maternal affective disorders in utero. Sixty cord blood DNA samples from the Boston Birth Cohort were genotyped at rs1360780 and studied for methylation changes as they relate to genotype and exposure to affective disorders during pregnancy. Linear regression was employed to contrast the risk (TT) genotype to the heterozygous (CT) and homozygous (CC) genotypes with adjustment for potential confounders. The recessive genotype (TT) was associated with increased methylation at multiple CpGs in the FKBP5 intron 5 region (p < 0.01). These findings were enhanced among cases exposed to maternal affective disorders (p = 0.02). A human cell line treated with cortisol showed that changes in intron 5 CpG methylation and FKBP5 expression were inversely associated. These findings suggest that rs1360780 can influence FKBP5 intronic methylation by acting in cis as a methylation quantitative locus and highlight the impact of genotypic risk on methylation in utero. Additionally, prenatal stress exposure compounded with the risk genotype may lead to a compensatory increase in methylation.

Insulin resistance (IR) underlies metabolic disease. Visceral, but not subcutaneous, white adipose tissue (WAT) has been linked to the development of IR, potentially due to differences in regulatory protein abundance. Here we investigate how protein levels are changed in IR in different WAT depots by developing a targeted proteomics approach to quantitatively compare the abundance of 42 nuclear proteins in subcutaneous and visceral WAT from a commonly used insulin-resistant mouse model, Lepr(db/db), and from C57BL/6J control mice. The most differentially expressed proteins were important in adipogenesis, as confirmed by siRNA-mediated depletion experiments, suggesting a defect in adipogenesis in visceral, but not subcutaneous, insulin-resistant WAT. Furthermore, differentiation of visceral, but not subcutaneous, insulin-resistant stromal vascular cells (SVCs) was impaired. In an in vitro approach to understand the cause of this impaired differentiation, we compared insulin-resistant visceral SVCs to preadipocyte cell culture models made insulin resistant by different stimuli. The insulin-resistant visceral SVC protein abundance profile correlated most with preadipocyte cell culture cells treated with both palmitate and TNFα. Together, our study introduces a method to simultaneously measure and quantitatively compare nuclear protein expression patterns in primary adipose tissue and adipocyte cell cultures, which we show can reveal relationships between differentiation and disease states of different adipocyte tissue types.

Objective: The current study longitudinally examines college student Twitter patterns throughout initial phases of the COVID-19 pandemic. This study aims to better understand psychological impact and online personal communication during the pandemic. Participants: A dataset consisting of ~720,000 tweets posted by students from universities throughout the United States during the 2020 spring semester was analyzed according to structural and sentimental analysis. Methods: Using a data-driven approach, three time periods emerged which reflected the transition to online learning. Results: Significant changes in structure and sentiment of tweets were observed across phases. Conclusions: Changes in Twitter patterns revealed important features of this unprecedented transition to online learning for college students.

Emotional distracters impair cognitive function. Emotional processing is dysregulated in affective disorders such as depression, phobias, schizophrenia, and PTSD. Among the processes impaired by emotional distracters, and whose dysregulation is documented in affective disorders, is the ability to time in the seconds-to-minutes range, i.e. interval timing. Presentation of task-irrelevant distracters during a timing task results in a delay in responding suggesting a failure to maintain subjective time in working memory, possibly due to attentional and working memory resources being diverted away from timing, as proposed by the Relative Time-Sharing model. We investigated the role of the prelimbic cortex in the detrimental effect of anxiety-inducing task-irrelevant distracters on the cognitive ability to keep track of time, using local infusions of norepinephrine and dopamine reuptake inhibitor nomifensine in a modified peak-interval procedure with neutral and anxiety-inducing distracters. Given that some antidepressants have beneficial effects on attention and working memory, e.g., decreasing emotional response to negative events, we hypothesized that nomifensine would improve maintenance of information in working memory in trials with distracters, resulting in a decrease of the disruptive effect of emotional events on the timekeeping abilities. Our results revealed a dissociation of the effects of nomifensine infusion in prelimbic cortex between interval timing and resource allocation, and between neutral and anxiety-inducing distraction. Nomifensine was effective only during trials with distracters, but not during trials without distracters. Nomifensine reduced the detrimental effect of the distracters only when the distracters were anxiety-inducing, but not when they were neutral. Results are discussed in relation to the brain circuits involved in Relative Time-Sharing of resources, and the pharmacological management of affective disorders.