Search

Organizational transformation takes time, energy, and patience. An active administrative unit, The Hub for Innovation in Learning and Technology (called simply, the Hub) engaged intentional change from its inception. The Hub aspires to help Michigan State University (MSU) "reinvent itself as a learning institution" by transforming ourselves so that we might transform others. The authors, all current employees of the Hub, provide an in-depth look into the challenges and triumphs of purposeful organizational change. Without change, MSU would maintain existing gaps on measures of student success among different demographic groups. The key audience of these efforts are learners in the university while considering the surrounding system of faculty, staff, administrators, curriculum, assessment, and student engagement efforts. The Hub catalyzes innovative ways to collaborate, learn, research, and improve learning. We design new opportunities that take advantage of skills and connections across the disciplines. The Hub adapted work practices that can sustain transformation. The Hub also built a physical space reflective of these strategies. Initial practices resulted in a series of careful, bold learning pathways focused on new capacity and professional development for stakeholders. We extrapolated experiences, practices, and findings for other transforming university, business, and organizational contexts.

A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

CRISPR-Cas-guided base editors convert A•T to G•C, or C•G to T•A, in cellular DNA for precision genome editing. To understand the molecular basis for DNA adenosine deamination by adenine base editors (ABEs), we determined a 3.2-angstrom resolution cryo-electron microscopy structure of ABE8e in a substrate-bound state in which the deaminase domain engages DNA exposed within the CRISPR-Cas9 R-loop complex. Kinetic and structural data suggest that ABE8e catalyzes DNA deamination up to ~1100-fold faster than earlier ABEs because of mutations that stabilize DNA substrates in a constrained, transfer RNA-like conformation. Furthermore, ABE8e's accelerated DNA deamination suggests a previously unobserved transient DNA melting that may occur during double-stranded DNA surveillance by CRISPR-Cas9. These results explain ABE8e-mediated base-editing outcomes and inform the future design of base editors.

CRISPR-Cas systems are found widely in prokaryotes, where they provide adaptive immunity against virus infection and plasmid transformation. We describe a minimal functional CRISPR-Cas system, comprising a single ~70-kilodalton protein, CasΦ, and a CRISPR array, encoded exclusively in the genomes of huge bacteriophages. CasΦ uses a single active site for both CRISPR RNA (crRNA) processing and crRNA-guided DNA cutting to target foreign nucleic acids. This hypercompact system is active in vitro and in human and plant cells with expanded target recognition capabilities relative to other CRISPR-Cas proteins. Useful for genome editing and DNA detection but with a molecular weight half that of Cas9 and Cas12a genome-editing enzymes, CasΦ offers advantages for cellular delivery that expand the genome editing toolbox.

The increasing use of CRISPR-Cas9 in medicine, agriculture, and synthetic biology has accelerated the drive to discover new CRISPR-Cas inhibitors as potential mechanisms of control for gene editing applications. Many anti-CRISPRs have been found that inhibit the CRISPR-Cas adaptive immune system. However, comparing all currently known anti-CRISPRs does not reveal a shared set of properties for facile bioinformatic identification of new anti-CRISPR families. Here, we describe AcRanker, a machine learning based method to aid direct identification of new potential anti-CRISPRs using only protein sequence information. Using a training set of known anti-CRISPRs, we built a model based on XGBoost ranking. We then applied AcRanker to predict candidate anti-CRISPRs from predicted prophage regions within self-targeting bacterial genomes and discovered two previously unknown anti-CRISPRs: AcrllA20 (ML1) and AcrIIA21 (ML8). We show that AcrIIA20 strongly inhibits Streptococcus iniae Cas9 (SinCas9) and weakly inhibits Streptococcus pyogenes Cas9 (SpyCas9). We also show that AcrIIA21 inhibits SpyCas9, Streptococcus aureus Cas9 (SauCas9) and SinCas9 with low potency. The addition of AcRanker to the anti-CRISPR discovery toolkit allows researchers to directly rank potential anti-CRISPR candidate genes for increased speed in testing and validation of new anti-CRISPRs. A web server implementation for AcRanker is available online at http://acranker.pythonanywhere.com/.

Lung cancer screening via low-dose computed tomography (LDCT) has been underutilized by high-risk current and former smokers since its approval in 2013. Further, lower use of other evidence-based cancer screening tests (e.g., colorectal cancer, breast cancer) has been noted among African Americans when compared with other racial and ethnic groups. Reasons for low uptake are multilayered but include the need for consideration of patients' personal values about the screening decision. The goal of the present study was to (1) identify positive and negative factors specific to lung cancer screening via LDCT and (2) develop statements to capture values about the screening test for use in a new measure of decisional values. Key informant interviews (n = 9) identified several benefits and risks of lung cancer screening that may be important to African American smokers. Based on these interviews, a pool of items with the values statements was administered to a convenience sample of 119 African Americans [aged 55-80 years, current or former smokers (who quit

Undergraduate students, particularly those with limited experience in business, struggle to appreciate the complexity of organizational communication dynamics. Communication complexities such as role conflict, position power, and individual perception--and their influence on effective communication--are particularly challenging for this population. This article describes a classroom exercise based on the children's game "Telephone" that connects organizational communication with considerations of role conflict, power and influence tactics, and individual perceptions as they influence engagement with communication involving a new initiative. During the full class reflection and debrief, students identify the connections between their role in the activity and how individual organizational elements and experiences may inform effective communication. Designed for an undergraduate organizational behavior course, the exercise is adaptable to other management topics or levels where communication is a consideration.

Although statistically unlikely, early-onset breast cancer tends to be more aggressive and leads to greater mortality than breast cancer among women of screening age. Young African American women are disproportionately impacted by early-onset breast cancer compared to women of other races. Given the racial disparities and because young women are typically not the primary audience for breast cancer educational messaging, there is a need to identify recommendations for age-appropriate breast cancer education for African American women below mammogram eligibility. Through N = 30 key informant interviews with young African American breast cancer survivors, family members of young survivors, community organization leaders and healthcare providers, we identified breast cancer educational message content and communication channels relevant for these women. Participants recommended that message content should emphasize the need to address family cancer history and self-advocacy in healthcare encounters in addition to concerns about loss of womanhood, financial costs and opportunity costs associated with preventive healthcare visits. Breast cancer messages for this audience should consider the influences of earlier life stage, culture and race. Recommended communication channels highlighted use of social media and videos. Findings will inform future age-appropriate educational messaging aimed at eliminating early-onset breast cancer disparities disproportionately impacting young African American women.