Activity

The last stage of cell division involves two daughter cells remaining interconnected by a cytokinetic bridge that is cleaved during abscission. Conserved between the zebrafish embryo and human cells, we found that the oldest centrosome moves in a Rab11-dependent manner towards the cytokinetic bridge sometimes followed by the youngest. Rab11-endosomes are organized in a Rab11-GTP dependent manner at the mother centriole during pre-abscission, with Rab11 endosomes at the oldest centrosome being more mobile compared with the youngest. The GTPase activity of Rab11 is necessary for the centrosome protein, Pericentrin, to be enriched at the centrosome. Reduction in Pericentrin expression or optogenetic disruption of Rab11-endosome function inhibited both centrosome movement towards the cytokinetic bridge and abscission, resulting in daughter cells prone to being binucleated and/or having supernumerary centrosomes. These studies suggest that Rab11-endosomes contribute to centrosome function during pre-abscission by regulating Pericentrin organization resulting in appropriate centrosome movement towards the cytokinetic bridge and subsequent abscission.Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics and potential functions of lncRNAs with shared synteny remains unclear. Here we show that the syntenically conserved lncRNA Firre displays distinct expression and localization patterns in human and mouse. Single molecule RNA FISH reveals that in a range of cell lines, mouse Firre (mFirre) is predominantly nuclear, while human FIRRE (hFIRRE) is distributed between the cytoplasm and nucleus. This localization pattern is maintained in human/mouse hybrid cells expressing both human and mouse Firre, implying that the localization of the lncRNA is species autonomous. We find that the majority of hFIRRE transcripts in the cytoplasm are comprised of isoforms that are enriched in RRD repeats. We furthermore determine that in various tissues, mFirre is more highly expressed than its human counterpart. Our data illustrate that the rapid evolution of syntenic lncRNAs can lead to variations in lncRNA localization and abundance, which in turn may result in disparate lncRNA functions even in closely related species.Accurate prioritization of immunogenic neoantigens is key to developing personalized cancer vaccines and distinguishing those patients likely to respond to immune checkpoint inhibition. However, there is no consensus regarding which characteristics best predict neoantigen immunogenicity, and no model to date has both high sensitivity and specificity and a significant association with survival in response to immunotherapy. We address these challenges in the prioritization of immunogenic neoantigens by (1) identifying which neoantigen characteristics best predict immunogenicity; (2) integrating these characteristics into an immunogenicity score, the NeoScore; and (3) demonstrating a significant association of the NeoScore with survival in response to immune checkpoint inhibition. One thousand random and evenly split combinations of immunogenic and nonimmunogenic neoantigens from a validated dataset were analyzed using a regularized regression model for characteristic selection. The selected characteristics, the dissociation constant and binding stability of the neoantigenMHC class I complex and expression of the mutated gene in the tumor, were integrated into the NeoScore. A web application is provided for calculation of the NeoScore. The NeoScore results in improved, or equivalent, performance in four test datasets as measured by sensitivity, specificity, and area under the receiver operator characteristics curve compared with previous models. Among cutaneous melanoma patients treated with immune checkpoint inhibition, a high maximum NeoScore was associated with improved survival. Overall, the NeoScore has the potential to improve neoantigen prioritization for the development of personalized vaccines and contribute to the determination of which patients are likely to respond to immunotherapy.IL-22 is a multifaceted cytokine with both pro- and anti-inflammatory functions that is implicated in multiple pathologies. However, the role of IL-22 in maternal-fetal immunity in late gestation is poorly understood. In this study, we first showed that IL-22+ T cells coexpressing retinoic acid-related orphan receptor γt (ROR-γt) are enriched at the human maternal-fetal interface of women with preterm labor and birth, which was confirmed by in silico analysis of single-cell RNA sequencing data. T cell activation leading to preterm birth in mice was preceded by a surge in IL-22 in the maternal circulation and amniotic cavity; however, systemic administration of IL-22 in mice did not induce adverse perinatal outcomes. Next, using an ex vivo human system, we showed that IL-22 can cross from the choriodecidua to the intra-amniotic space, where its receptors (Il22ra1, Il10rb, and Il22ra2) are highly expressed by murine gestational and fetal tissues in late pregnancy. Importantly, amniotic fluid concentrations of IL-22 were elevated in women with sterile or microbial intra-amniotic inflammation, suggesting a dual role for this cytokine. The intra-amniotic administration of IL-22 alone shortened gestation and caused neonatal death in mice, with the latter outcome involving lung maturation and inflammation. IL-22 plays a role in host response by participating in the intra-amniotic inflammatory milieu preceding Ureaplasma parvum-induced preterm birth in mice, which was rescued by the deficiency of IL-22. Collectively, these data show that IL-22 alone is capable of causing fetal injury leading to neonatal death and can participate in host defense against microbial invasion of the amniotic cavity leading to preterm labor and birth.Objective. To determine if students’ levels of resilience and self-reported wellness behaviors predict burnout and grade point average (GPA) at the end of the first fall semester of the COVID-19 pandemic.Methods. We measured first-year students’ resilience, burnout (exhaustion and disengagement), and self-reported wellness behaviors (sleep, nutrition, social time, and self-care activities) at the beginning and end of the fall 2020 semester of pharmacy school. We also collected students’ demographic information and obtained end-of-semester GPA from their academic records. Using multivariable regression, we assessed whether students’ resilience and wellness behaviors predicted burnout and GPA at the end of the semester. We also assessed for changes in burnout and wellness behaviors over time.Results. Resilience was positively associated with older age and was lower among students of color. Exhaustion and disengagement were high at baseline and continued to worsen over time. Students’ self-reported wellness behaviors also decreased over time, except for ratings of sleep adequacy. Resilience predicted lower levels of disengagement at the end of the semester, but its relationship with exhaustion was inconsistent. The only wellness behaviors associated with lower burnout were nutrition and sleep adequacy. Students’ end-of-semester GPA was also related to nutrition and sleep adequacy but not resilience or burnout.Conclusion. Resilience offered some protection from burnout, but its relationship to immutable factors suggests that individual-focused interventions to improve student well-being (eg, wellness behaviors such as mindfulness meditation) should be complemented by organizational support, especially for younger students and students of color.Objective. Pharmacy programs have struggled to predict who will be successful in their programs based solely on cognitive skills. The primary objective of this study was to determine which, if any, non-academic factors are associated with on-time progression within the school of pharmacy (SOP) curriculum.Methods. A survey was developed and offered to all Texas Tech University Health Sciences Center Jerry H. Hodge SOP students in Fall 2020. This survey included questions to collect demographic data and incorporated four validated questionnaires which included the (1) Grit-Grid, (2) Academic Pharmacy Resilience Scale (APRS-16), (3) Cohen Perceived Stress Scale (CPSS), and (4) Turkish Time Management Questionnaire (TTMQ).Results. Completed surveys were submitted by 213 students out of 569 (37.4% response rate). On-time progression rate was calculated separately for each class. Through binary logistic regression, pre-pharmacy grade point average >3.20, high school `Grit-Grid score >0.9, APRS-16 score >35, and CPSS >34 were significantly associated with on-time progression. PCAT composite scores and admissions committee rubric scores were not associated with on-time progression.Conclusion. Based on the results of this study, it may be reasonable to implement the Grit-Grid, APRS-16 and the CPSS in the admissions process to help determine the most appropriate candidates for our program or use them as screening tools for incoming students to identify who may be at academic risk. However, these factors need to be validated in pharmacy programs in other private and public universities before widespread adoption can be condoned.

Despite increased participation of women in academic medicine in recent decades, gender disparities persist. The gender gap in authorship and editorial boards in gynecologic oncology, and impact of the COVID-19 pandemic, have not been recently evaluated. We examined gender representation and the impact of COVID-19 on authorship and editorial boards of two major peer-reviewed gynecologic oncology journals.

We conducted a bibliometric analysis of original articles published in

and the

comparing the most contemporary 5-year period (2016-2020) to single years in the two prior decades (1996, 2006). To assess the early impact of COVID-19, we compared publications from May 2020-April 2021 to 2019. Editorial boards were analyzed for gender composition. First names, pronouns, and institutional photographs were used to determine gender.

There were 3022 original articles published between 2016 and 2020, 763 in 2006, and 203 in 1996. Gender was identified for 91.3% of first authors (3641 articles) and 95.6% o and editorial board representation. This presents an opportunity for the academic publishing community to advocate for deliberate strategies to achieve gender parity. Although no impact of the early COVID-19 pandemic was found, this requires ongoing surveillance.

To assess the humoral response to messenger RNA (mRNA) vaccine of patients with systemic autoimmune rheumatic disease (SARD) and the effect of immunosuppressive medication in a matched cohort study.

Patients with SARD were enrolled and matched 11 for sex and age with healthy control (HC) subjects. Differences in humoral response to two doses of an mRNA vaccine in terms of seroconversion rate (SCR) and SARS-CoV-2 antibody level between the two groups and the impact of treatment within patients with SARD were assessed.

We enrolled 82 patients with SARD and 82 matched HC. SCR after the first dose was lower among the patient group than that of HC (65% compared with 100% in HC, p<0.0001) but levelled up after the second dose (94% vs 100%). MRTX1719 purchase After the second dose, SCR was lower for patients on combination disease-modifying antirheumatic drug (DMARD) therapy compared with all other groups (81% compared with 95% for monotherapy, p=0.01; 100% for both no DMARD therapy and HC, both p<0.0001). In addition, antibody levels after both doses were lower in patients compared with HC.