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Abstract As the COVID-19 pandemic enters its fourth year, the pursuit of identifying a progenitor virus to SARS-CoV-2 and understanding the mechanism of its emergence persists, albeit against the backdrop of intensified efforts to monitor the ongoing evolution of the virus and the influx of new mutations. Surprisingly, few residues hypothesized to be essential for SARS-CoV-2 emergence and adaptation to humans have been validated experimentally, despite the importance that these mutations could contribute to the development of effective antivirals. To remedy this, we searched for genomic regions in the SARS-CoV-2 genome that show evidence of past selection around residues unique to SARS-CoV-2 compared with closely related coronaviruses. In doing so, we identified a residue at position 519 in Spike within the receptor binding domain that holds a static histidine in human-derived SARS-CoV-2 sequences but an asparagine in SARS-related coronaviruses from bats and pangolins. In experimental validation, the SARS-CoV-2 Spike protein mutant carrying the putatively ancestral H519N substitution showed reduced replication in human lung cells, suggesting that the histidine residue contributes to viral fitness in the human host. Structural analyses revealed a potential role of Spike residue 519 in mediating conformational transitions necessary for Spike prior to binding with ACE2. Pseudotyped viruses bearing the putatively ancestral N519 also demonstrated significantly reduced infectivity in cells expressing the human ACE2 receptor compared to H519. ELISA data corroborated that H519 enhances Spike binding affinity to the human ACE2 receptor compared to the putatively ancestral N519. Collectively, these findings suggest that the evolutionary transition at position 519 of the Spike protein played a critical role in SARS-CoV-2 emergence and adaptation to the human host. Additionally, this residue presents as a potential drug target for designing small molecule inhibitors tailored to this site.

Sex estimation of skeletons is fundamental to many archaeological studies. Currently, three approaches are available to estimate sex-osteology, genomics, or proteomics, but little is known about the relative reliability of these methods in applied settings. We present matching osteological, shotgun-genomic, and proteomic data to estimate the sex of 55 individuals, each with an independent radiocarbon date between 2,440 and 100 cal BP, from two ancestral Ohlone sites in Central California. Sex estimation was possible in 100% of this burial sample using proteomics, in 91% using genomics, and in 51% using osteology. Agreement between the methods was high, however conflicts did occur. Genomic sex estimates were 100% consistent with proteomic and osteological estimates when DNA reads were above 100,000 total sequences. However, more than half the samples had DNA read numbers below this threshold, producing high rates of conflict with osteological and proteomic data where nine out of twenty conditional DNA sex estimates conflicted with proteomics. While the DNA signal decreased by an order of magnitude in the older burial samples, there was no decrease in proteomic signal. We conclude that proteomics provides an important complement to osteological and shotgun-genomic sex estimation.

Currently, there is great interest across Ontario in the expansion of pathway programs between colleges and universities. Through strategic partnerships, two Ontario-based postsecondary institutions (a college and a university) have developed innovative and effective pathway programs that facilitate the transition of students between institutions for the completion of degrees, diplomas, and certificates. These programs support the training of highly qualified, market-ready graduates. This paper reports on a mixed-methods study of the successes and challenges of a particular Ontario college and university pathway program, with a focus on the Bachelor of Commerce Pathway program. Preliminary results indicate that pathway students were more academically successful than their traditional university student counterparts but did experience a number of challenges in transitioning from college into university. Principal challenges included inefficient communication between program administrators, academic advisors, and students; lack of orientation activities for pathway students; lack of college student preparedness in communication and critical thinking skills; and difficulties experienced by college students integrating into the social-cultural life of the university.

This study evaluates the impact of a College to University Pathway Program in the Faculty of Social Science and Humanities at The University of Ontario Institute of Technology. The findings support the assertion that Pathway students perform as well as or better than students who enter university directly from secondary school. This finding is encouraging for universities and colleges as they work toward developing additional Pathway Programs and improving the Pathway Programs they may already offer.

The purpose of this study was to compare community college students' learning experiences and performance for lecture-based, active learning, and flipped classroom teaching approaches. Participants were second-semester computer programming students (n = 103) at a mid-sized college of applied arts and technology. Garrison's (2011) Community of Inquiry (CoI) framework informed our analysis of students' learning experiences within each approach. Overall, active learning resulted in the highest mean scores for teaching, social, and cognitive presence. In particular, students rated teaching presence significantly higher for the active-learning approach than the lecture-based approach. Students rated social presence significantly higher for the active-learning and flipped classroom approaches compared to the lecture-based. There were no significant differences among the three approaches with respect to cognitive presence or learning performance. Student comments indicated that all three approaches had distinct benefits and challenges regarding teaching, social and cognitive presence. Regardless of the teaching approach employed in this study, five desired learning characteristics emerged based on student feedback including clarity, flexibility, opportunities for application, timely guidance and feedback, and cognitive engagement.

Summary: Post-translational modification of ribosomal subunit proteins (RPs) is emerging as an important means of regulating gene expression. Recently, regulatory ubiquitination of small RPs RPS10 and RPS20 by the ubiquitin ligase ZNF598 was found to function in ribosome sensing and stalling on internally polyadenylated mRNAs during ribosome quality control (RQC). Here, we reveal that ZNF598 and RPS10 negatively regulate interferon-stimulated gene (ISG) expression in primary cells, depletion of which induced ISG expression and a broad antiviral state. However, cell lines lacking interferon responses revealed that ZNF598 E3 ligase activity and ubiquitination of RPS20, but not RPS10, were specifically required for poxvirus replication and synthesis of poxvirus proteins whose encoding mRNAs contain unusual 5′ poly(A) leaders. Our findings reveal distinct functions for ZNF598 and its downstream RPS targets, one that negatively regulates ISG expression and infection by a range of viruses while the other is positively exploited by poxviruses. : In addition to repressing poly(A) readthrough during ribosome quality control, DiGiuseppe et al. report that ZNF598 and RPS10 negatively regulate interferon-stimulated gene expression (ISG). However, in cell lines lacking ISG responses, ZNF598 ubiquitin ligase activity and RPS20 ubiquitination are specifically required by poxviruses, which produce unusual mRNAs with 5′ poly(A) leaders. Keywords: ZNF598, ubiquitination, ribosome, RPS, post-translational modification, specialization, translation, virus, poxvirus

Purpose: The purpose of this paper is to explore not only the academic measures such as grade point average of success of college-to-university transfer programs (Pathway Programs), but also the social-cultural facilitators and barriers throughout the students' Pathway experience. Design/methodology/approach: The experience of students and academic advisors moving between Queensdale College and North Star University (NSU) (pseudonyms) were analyzed using a mixed-methods approach including analysis of data from online surveys, secondary data (course performance), and focus group interviews. Findings: Students who are able to enter the Pathway Programs at NSU perform on average better than their four-year traditional program peers. There remain a number of social-cultural barrier which need to be addressed to improve the overall experience of these transfer students. Practical implications: The results from this study will assist the administrative decision makers in designing Pathways and their associated communication plans in order to meet the needs of the students with tools and supports that are both perceived by the students as valuable and are improving their Pathway experience and ultimately their academic performance. Originality/value: The move to develop Pathway Programs in Ontario is a new phenomenon, even in provinces where this is more common, few studies exist which consider the social-cultural aspects of the student journey between the two institutions. This study moves beyond the standard academic performance data and provides insight into the critical role played by the social aspects in higher education experiences.

Abstract The integration of digital technologies at institutions of higher education are profoundly influencing formal learning on a global scale. Social-constructivist models of fully online learning are well-positioned to address the demands of government, and economic and social-development organizations for civically-engaged individuals with strong problem-solving, critical-thinking and collaboration competencies. With an established record of performance at the University of Ontario Institute of Technology (UOIT), Canada, the Fully Online Learning Community (FOLC) is one such model. This paper theorizes FOLC as a response to several problematics, including (a) the aforementioned demand for greater educational focus on higher-order competency development, (b) the deficiencies of distance education and MOOCs as learning models, and (c) a quest for new learning models that strengthen deliberation skills and deepen democratic experience. As a divergent fork of the Community of Inquiry model, FOLC describes collaborative learning as a symbiosis of social and cognitive interactions amplified through effective use of synchronous and asynchronous digital affordances. Furthermore, it models democratized learning communities that reduce transactional distance between learners and educators, incorporates authentic assessment, and encourages negotiated technology affordances and cognitive outcomes while distributing responsibility for constructive criticality. Having positioned FOLC conceptually, and addressed current limitations, a research agenda for extending its empirical foundations, and leveraging UOIT’s EILAB affordances, is presented. The underlying argument is that self-regulating and transformative learning communities can be established and sustained in fully online environments, and that such communities (a) produce a diversity of beneficial learning outcomes, and (b) deepen the democratic functioning of learners and their social contexts.

Subnuclear promyelocytic leukemia (PML) nuclear bodies (NBs) are targeted by many DNA viruses after nuclear delivery. PML protein is essential for formation of PML NBs. Sp100 and Small Ubiquitin-Like Modifier (SUMO) are also permanently residing within PML NBs. Often, large DNA viruses disassemble and reorganize PML NBs to counteract their intrinsic antiviral activity and support establishment of infection. However, human papillomavirus (HPV) requires PML protein to retain incoming viral DNA in the nucleus for subsequent efficient transcription. In contrast, Sp100 was identified as a restriction factor for HPV. These findings suggested that PML NBs are important regulators of early stages of the HPV life cycle. Nuclear delivery of incoming HPV DNA requires mitosis. Viral particles are retained within membrane-bound transport vesicles throughout mitosis. The viral genome is released from transport vesicles by an unknown mechanism several hours after nuclear envelope reformation. The minor capsid protein L2 mediates intracellular transport by becoming transmembranous in the endocytic compartment. Herein, we tested our hypothesis that PML protein is recruited to incoming viral genome prior to egress from transport vesicles. High-resolution microscopy revealed that PML protein, SUMO-1, and Sp100 are recruited to incoming viral genomes, rather than viral genomes being targeted to preformed PML NBs. Differential immunofluorescent staining suggested that PML protein and SUMO-1 associated with transport vesicles containing viral particles prior to egress, implying that recruitment is likely mediated by L2 protein. In contrast, Sp100 recruitment to HPV-harboring PML NBs occurred after release of viral genomes from transport vesicles. The delayed recruitment of Sp100 is specific for HPV-associated PML NBs. These data suggest that the virus continuously resides within a protective environment until the transport vesicle breaks down in late G1 phase and imply that HPV might modulate PML NB assembly to achieve establishment of infection and the shift to viral maintenance.

Current reforms in elementary and secondary science education call for students and teachers to develop more informed views of the nature of science (NOS)--a process in which science textbooks play a significant role. This paper reports on a case study of the development of representations of the NOS in a senior high school chemistry textbook by the book's author, editor, and publisher. The study examines the multiple discourses that arose as the developers reflected on their personal and shared understandings of NOS; squared these with mandated curricula, the educational needs of chemistry students and teachers, and the exigencies of large-scale commercial textbook publishing. As a result, the team developed and incorporated, in the textbook, representations of NOS they believed were the most pedagogically suitable. Analysis of the data in this study indicates that a number of factors significantly influenced the development of representations of NOS, including representational accuracy (the degree to which representations of NOS conformed to informed views of the NOS), representational consistency (the degree to which representations of NOS in different parts of the book conveyed the same meaning), representational appropriateness (the age-, grade-, and reading-level appropriateness of the NOS representations), representational alignment (the degree to which NOS representations aligned with mandated curriculum), representational marketability (the degree to which NOS representations would affect sales of the textbook), and 'Workplace Resources' factors including availability of time, relevant expertise, and opportunities for professional development.

Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

The motivation of this investigation is to explore the possibility of using the depth profile capability of XPS to study interfaces after SOFC button cell testing. The literature uses XPS to study various cathode materials but has devoted little to the understanding of various cathode interfaces especially after testing. In this work, an SOFC button cell is first tested, and then, the LSCF cathode, barrier layer, and electrolyte are sputtered away to study the behavior of different interfaces. This work has shown that some elements have moved into other layers of the SOFC cell. It is argued that the migration of the elements is partly due to a redeposition mechanism after atoms are sputtered away, while the rest is due to interdiffusion between the SDC and YSZ layers. However, additional work is needed to better understand the mechanism by which atoms move around at different interfaces. The cell electrochemical performance is also discussed in some details but is not the focus.

This paper reports the study of an anode-supported SOFC cell containing an LSCF-SDC composite cathode. The SOFC cell was tested at different temperatures and reactant flow rates. After testing, the cell was sectioned and characterized using SEM/EDS. Such analysis indicated that no structural damage and no significant interdiffusion of elements among the layers occurred. The measured electrochemical performance data at different temperatures indicate an Arrhenius behavior or temperature activated processes. The low-porosity anode functional layer appears to be very sensitive to low hydrogen contents. The electrochemical performance is also affected by changing air flow rates.

Abstract Neoplastic B cells may have cytoplasmic inclusions that are visible in routine peripheral blood smears by light microscopy.

Santanello (2011) presented the case of a man with long-term anger problems who does not meet the criteria for any "DSM-IV-TR" diagnosis for treatment recommendations by several authors. This paper presents a comprehensive treatment package applied to this case. Of crucial importance is the building of a therapeutic alliance. In addition to refusing to agree to the goals and tasks of therapy, this client has intimidated several previous therapists. Strategies to build the alliance are discussed. Cognitive restructuring techniques aimed at the client's narcissistic needs for recognition by others and resentment about past abuses are all detailed. The use of imaginal exposure to anger triggers and strategies to learn new adaptive behaviors are also explored.

This study investigated the roles of coping and masculinity in higher rates of depressive symptoms among adolescent girls, as compared to boys. A model was designed and tested through path analysis, which involved the variables of sex, gender, problem-focused coping, rumination, and distraction. The Reynolds Adolescent Depression Scale and the Bem Sex Role Inventory, as well as a measure of coping with general stressors was completed by 246 adolescents. Results showed that adolescent girls were more depressed than boys, and that girls used more emotion-focused and ruminative coping than did boys. Greater degrees of ruminative coping were related to high levels of depressive symptoms. Problem-focused and distractive coping were positively correlated with masculinity and negatively associated with depression. Surprisingly, girls were more likely to use problem-focused coping. Problem-focused and distractive coping were found to mediate the negative relationship between masculinity and depression. (Contains 2 figures.)

This article applies the Principles of Empirically Supported Interventions (PESI) in counseling psychology to anger management with adults. The review suggests that there is empirical support for cognitive-behavioral interventions generally and for four specific interventions (relaxation, cognitive, behavioral skill enhancement, and combinations of these three interventions). Moderate effect sizes for these interventions were found on targeted anger measures and for all measures combined. The PESI proved to be flexible, multidimensional principles against which to assess counseling interventions and from which to identify what is known and what needs to be learned.

In the absence of any other lesions on the body, the diagnosis of localized genital psoriasis can be difficult, requiring further examinations including a biopsy. We report a case of psoriatic pseudobalanitis circinata triggered by a herpes virus infection, and we discuss the Koebner phenomenon and the therapeutic management of psoriasis of the genital area.

Nine members of the institute for Rational-Emotive Therapy's (REBT) International Training Standards and Review Committee predicted the status of REBT 25 to 50 years after the death of Albert Ellis. Will REBT continue to exist in its own right or be incorporated into newer forms of cognitive behavior therapy? (EMK)