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The purpose of this study was to examine factors impacting college student leadership development within a college of agriculture at the University of Missouri. This study employed descriptive relational survey methods to examine the impact of involvement factors (participation in organizations, community service and leadership education) on college student leadership development. The target population was all junior and senior students in the College of Agricutlure, Food and Natural Resources at the University of Missouri (N=1,124). Out of the calculated sample size (n=287), 107 participants completed the online instrument (37.3%). In the examination of the leadership outcomes, the greatest mean was reported for the outcome of commitment and the lowest mean was reported for the outcome of change. Most students were involved with two to five different organizations during their college career. A majority (92.5%) of the students reported that they have engaged in community service during their college career, although 44.9% of respondents did not participate in community service on a regular basis. Students responded as being involved in one to two short-term leadership education programs, but no long-term leadership education programs. Eight separate linear regression models were analyzed to determine the impact of involvement factors on the development of socially responsible leadership.

Purpose: To perform a scoping review to determine what is known about emotional intelligence (EI) in undergraduate medical education (UME). Two main questions were asked: (1) What medical student characteristics are associated with EI? Are there correlations with demographic or other factors?; and (2) What research studies have been done on EI in UME? For example, is there evidence EI changes over time as a result of personal experiences? Should EI be used as an admission criterion? Can EI improve as a result of experiences or deliberate interventions? Method: The authors searched four databases (PubMed, PsycInfo, Education Resources Information Center, and Web of Science) for all papers published up to and including December 2020. Two reviewers independently screened articles to determine if they met inclusion criteria. All authors extracted and analyzed data. Results: A set of 1520 papers on the topic of emotional intelligence was identified, with 119 papers meeting inclusion criteria. Most studies were done at international locations with only 17 done at US medical schools. Seventy-five were cohort or cross-sectional studies. Study populations were mixed among the studies, with year of medical study, inclusion of other healthcare students, and participation rates among the inter-study differences noted. Conclusions: Numerous gaps in the literature on EI exist with several points being clear: (1) there is disagreement on the definition of EI; (2) it is undetermined whether EI is a trait or an ability; and (3) there is marked variability among the instruments used to measure EI. It is also becoming apparent that using EI determination may be helpful as a component of the admission process, higher EI is likely related to improved clinical reasoning, and higher EI contributes to more effective stress management.

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.

BackgroundNicotine, the pharmacologically active substance in both tobacco and many electronic cigarette (e-cigarette) liquids, is responsible for the addiction that sustains cigarette smoking. With 8 million deaths worldwide annually, smoking remains one of the major causes of disability and premature death. However, nicotine also plays an important role in smoking cessation strategies.ObjectivesThe aim of this study was to develop a comprehensive, whole-body, physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of nicotine and its major metabolite cotinine, covering various routes of nicotine administration, and to simulate nicotine brain tissue concentrations after the use of combustible cigarettes, e-cigarettes, nicotine gums, and nicotine patches.MethodsA parent-metabolite, PBPK/PD model of nicotine for a non-smoking and a smoking population was developed using 91 plasma and brain tissue concentration-time profiles and 11 heart rate profiles. Among others, cytochrome P450 (CYP) 2A6 and 2B6 enzymes were implemented, including kinetics for CYP2A6 poor metabolizers.ResultsThe model is able to precisely describe and predict both nicotine plasma and brain tissue concentrations, cotinine plasma concentrations, and heart rate profiles. 100% of the predicted area under the concentration-time curve (AUC) and maximum concentration (Cmax) values meet the twofold acceptance criterion with overall geometric mean fold errors of 1.12 and 1.15, respectively. The administration of combustible cigarettes, e-cigarettes, nicotine patches, and nicotine gums was successfully implemented in the model and used to identify differences in steady-state nicotine brain tissue concentration patterns.ConclusionsOur PBPK/PD model may be helpful in further investigations of nicotine dependence and smoking cessation strategies. As the model represents the first nicotine PBPK/PD model predicting nicotine concentration and heart rate profiles after the use of e-cigarettes, it could also contribute to a better understanding of the recent increase in youth e-cigarette use.

IL-2 has been used to treat diseases ranging from cancer to autoimmune disorders, but its concurrent immunostimulatory and immunosuppressive effects hinder efficacy. IL-2 orchestrates immune cell function through activation of a high-affinity heterotrimeric receptor (composed of IL-2Rα, IL-2Rβ, and common γ [γc]). IL-2Rα, which is highly expressed on regulatory T (TReg) cells, regulates IL-2 sensitivity. Previous studies have shown that complexation of IL-2 with the JES6-1 Ab preferentially biases cytokine activity toward TReg cells through a unique mechanism whereby IL-2 is exchanged from the Ab to IL-2Rα. However, clinical adoption of a mixed Ab/cytokine complex regimen is limited by stoichiometry and stability concerns. In this study, through structure-guided design, we engineered a single agent fusion of the IL-2 cytokine and JES6-1 Ab that, despite being covalently linked, preserves IL-2 exchange, selectively stimulating TReg expansion and exhibiting superior disease control to the mixed IL-2/JES6-1 complex in a mouse colitis model. These studies provide an engineering blueprint for resolving a major barrier to the implementation of functionally similar IL-2/Ab complexes for treatment of human disease.

Delivery of bacterial toxins to host cells is hindered by host protective barriers. This obstruction dictates a remarkable efficiency of toxins, a single copy of which may kill a host cell. Efficiency of actin-targeting toxins is further hampered by an overwhelming abundance of their target. The actin cross-linking domain (ACD) toxins of Vibrio species and related bacterial genera catalyze the formation of covalently cross-linked actin oligomers. Recently, we reported that the ACD toxicity can be amplified via a multivalent inhibitory association of actin oligomers with actin assembly factors formins, suggesting that the oligomers may act as secondary toxins. Importantly, many proteins involved in nucleation, elongation, severing, branching, and bundling of actin filaments contain G-actin-binding Wiskott-Aldrich syndrome protein (WASP)-homology motifs 2 (WH2) organized in tandem and therefore may act as a multivalent platform for high-affinity interaction with the ACD-cross-linked actin oligomers. Using live-cell single-molecule speckle (SiMS) microscopy, total internal reflection fluorescence (TIRF) microscopy, and actin polymerization assays, we show that, in addition to formins, the oligomers bind with high affinity and potently inhibit several families of actin assembly factors: Ena/vasodilator-stimulated phosphorprotein (VASP); Spire; and the Arp2/3 complex, both in vitro and in live cells. As a result, ACD blocks the actin retrograde flow and membrane dynamics and disrupts association of Ena/VASP with adhesion complexes. This study defines ACD as a universal inhibitor of tandem-organized G-actin binding proteins that overcomes the abundance of actin by redirecting the toxicity cascade toward less abundant targets and thus leading to profound disorganization of the actin cytoskeleton and disruption of actin-dependent cellular functions.

Biomolecules exist and function in cellular microenvironments that control their spatial organization, local concentration, and biochemical reactivity. Due to the complexity of native cytoplasm, the development of artificial bioreactors and cellular mimics to compartmentalize, concentrate, and control the local physico-chemical properties is of great interest. Here, we employ self-assembling polypeptide coacervates to explore the partitioning of the ubiquitous cytoskeletal protein actin into liquid polymer-rich droplets. We find that actin spontaneously partitions into coacervate droplets and is enriched by up to ∼30-fold. Actin polymerizes into micrometer-long filaments and, in contrast to the globular protein BSA, these filaments localize predominately to the droplet periphery. We observe up to a 50-fold enhancement in the actin filament assembly rate inside coacervate droplets, consistent with the enrichment of actin within the coacervate phase. Together these results suggest that coacervates can serve as a versatile platform in which to localize and enrich biomolecules to study their reactivity in physiological environments.

Ewing sarcoma (ES) involves a tumor-specific chromosomal translocation that produces the EWS-FLI1 protein, which is required for the growth of ES cells both in vitro and in vivo. However, an EWS-FLI1-driven transgenic mouse model is not currently available. Here, we present data from six independent laboratories seeking an alternative approach to express EWS-FLI1 in different murine tissues. We used the Runx2, Col1a2.3, Col1a3.6, Prx1, CAG, Nse, NEFL, Dermo1, P0, Sox9 and Osterix promoters to target EWS-FLI1 or Cre expression. Additional approaches included the induction of an endogenous chromosomal translocation, in utero knock-in, and the injection of Cre-expressing adenovirus to induce EWS-FLI1 expression locally in multiple lineages. Most models resulted in embryonic lethality or developmental defects. EWS-FLI1-induced apoptosis, promoter leakiness, the lack of potential cofactors, and the difficulty of expressing EWS-FLI1 in specific sites were considered the primary reasons for the failed attempts to create a transgenic mouse model of ES.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance.

We analyzed data from 3,546 occurrence records of Fire Salamanders (Salamandra salamandra) from the territory of the Czech Republic where it has a heterogeneous distribution pattern. Its occurrence in terrestrial habitats adjacent to breeding streams is characterized by a mean distance of 103 m, maximum 1,321 m, from the nearest stream. Based on a logistic GLM (generalized linear model) analysis we determined the Fire Salamanders' climatic and habitat associations at landscape scale in the Czech Republic. The main limiting factors for its dispersal include the proximity of small shallow streams in rolling landscapes, the pH of these streams, the presence of broad-leaf or mixed forests, humidity, solar irradiation, and severity of winters. While the absence of suitable breeding habitats is the main limiting factor for their occurrence in more expansive lowlands, factors such as lower temperatures, lower humidity, and the absence of broad-leaf and mixed forests begin to play a role with increasing altitude. Unlike cold temperatures, low amounts of precipitation and higher temperatures do not act as limiters in the Czech Republic. Fire Salamanders respond to the colder climate of higher altitudes with intensified summer activity and the purely bimodal nature of their activity (with spring and autumn peaks) tends to fade at higher altitudes. [ABSTRACT FROM AUTHOR]

Manduca sexta, known as the tobacco hornworm or Carolina sphinx moth, is a lepidopteran insect that is used extensively as a model system for research in insect biochemistry, physiology, neurobiology, development, and immunity. One important benefit of this species as an experimental model is its extremely large size, reaching more than 10 g in the larval stage. M. sexta larvae feed on solanaceous plants and thus must tolerate a substantial challenge from plant allelochemicals, including nicotine. We report the sequence and annotation of the M. sexta genome, and a survey of gene expression in various tissues and developmental stages. The Msex_1.0 genome assembly resulted in a total genome size of 419.4 Mbp. Repetitive sequences accounted for 25.8% of the assembled genome. The official gene set is comprised of 15,451 protein-coding genes, of which 2498 were manually curated. Extensive RNA-seq data from many tissues and developmental stages were used to improve gene models and for insights into gene expression patterns. Genome wide synteny analysis indicated a high level of macrosynteny in the Lepidoptera. Annotation and analyses were carried out for gene families involved in a wide spectrum of biological processes, including apoptosis, vacuole sorting, growth and development, structures of exoskeleton, egg shells, and muscle, vision, chemosensation, ion channels, signal transduction, neuropeptide signaling, neurotransmitter synthesis and transport, nicotine tolerance, lipid metabolism, and immunity. This genome sequence, annotation, and analysis provide an important new resource from a well-studied model insect species and will facilitate further biochemical and mechanistic experimental studies of many biological systems in insects.