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"Christensen, Kimberly"
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The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-β signaling
Inappropriate activation of developmental pathways is a well-recognized tumor-promoting mechanism. Here we show that overexpression of the homeoprotein Six1, normally a developmentally restricted transcriptional regulator, increases TGF-beta signaling in human breast cancer cells and induces an epithelial-mesenchymal transition (EMT) that is in part dependent on its ability to increase TGF-beta signaling. TGF-beta signaling and EMT have been implicated in metastatic dissemination of carcinoma. Accordingly, we used spontaneous and experimental metastasis mouse models to demonstrate that Six1 overexpression promotes breast cancer metastasis. In addition, we show that, like its induction of EMT, Six1-induced experimental metastasis is dependent on its ability to activate TGF-beta signaling. Importantly, in human breast cancers Six1 correlated with nuclear Smad3 and thus increased TGF-beta signaling. Further, breast cancer patients whose tumors overexpressed Six1 had a shortened time to relapse and metastasis and an overall decrease in survival. Finally, we show that the effects of Six1 on tumor progression likely extend beyond breast cancer, since its overexpression correlated with adverse outcomes in numerous other cancers including brain, cervical, prostate, colon, kidney, and liver. Our findings indicate that Six1, acting through TGF-beta signaling and EMT, is a powerful and global promoter of cancer metastasis.
Journal Article
Characteristics and Timing of Initial Virus Shedding in Severe Acute Respiratory Syndrome Coronavirus 2, Utah, USA
Virus shedding in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur before onset of symptoms; less is known about symptom progression or infectiousness associated with initiation of viral shedding. We investigated household transmission in 5 households with daily specimen collection for 5 consecutive days starting a median of 4 days after symptom onset in index patients. Seven contacts across 2 households implementing no precautionary measures were infected. Of these 7, 2 tested positive for SARS-CoV-2 by reverse transcription PCR on day 3 of 5. Both had mild, nonspecific symptoms for 1-3 days preceding the first positive test. SARS-CoV-2 was cultured from the fourth-day specimen in 1 patient and from the fourth- and fifth-day specimens in the other. We also describe infection control measures taken in the households that had no transmission. Persons exposed to SARS-CoV-2 should self-isolate, including from household contacts, wear a mask, practice hand hygiene, and seek testing promptly.
Journal Article
The Six1 Homeoprotein Stimulates Tumorigenesis by Reactivation of Cyclin A1
Homeobox genes constitute a large family of transcription factors that are essential during normal development and are often dysregulated in cancer. However, the molecular mechanisms by which homeobox genes influence cancer remain largely unknown. Here we show that the tissue-restricted cyclin A1 is a transcriptional target of the Six1 homeoprotein. Both genes are expressed in the embryonic but not the terminally differentiated mammary gland, and Six1-knockout mice show a dramatic reduction of cyclin A1 in the embryonic mammary gland. In addition, both genes are reexpressed in breast cancers. Six1 overexpression increases cyclin A1 mRNA levels and activity, cell proliferation, and tumor volume, whereas Six1 down-regulation decreases cyclin A1 mRNA levels and proliferation. Overexpression of Six1 in wild-type mouse embryonic fibroblasts, but not in knockout variants lacking the cyclin A1 gene, induces cell proliferation. Furthermore, inhibition of cyclin A1 in Six1-overexpressing mammary carcinoma cells decreases proliferation. Together these results demonstrate that cyclin A1 is required for the proliferative effect of Six1. We conclude that Six1 overexpression reinstates an embryonic pathway of proliferation in breast cancer by up-regulating cyclin A1.
Journal Article
DEC Personnel Preparation Standards
The revision and process of validation of standards for early childhood special education (ECSE) and early intervention (EI) personnel at the initial and advanced levels of preparation, which occurred during 2005-2008, are described to provide a record of the process and to inform future cycles of standards revision. Central components focus on the importance of the relationships forged in the process, especially with Council for Exceptional Children, and their contributions to its success. The results are discussed in terms of changes in terminology for the ECSE/EI standards, limitations of the process, and suggestions for next revisions.
Journal Article
Detection of SARS-CoV-2 on Surfaces in Households of Persons with COVID-19
SARS-CoV-2 transmission from contaminated surfaces, or fomites, has been a concern during the COVID-19 pandemic. Households have been important sites of transmission throughout the COVID-19 pandemic, but there is limited information on SARS-CoV-2 contamination of surfaces in these settings. We describe environmental detection of SARS-CoV-2 in households of persons with COVID-19 to better characterize the potential risks of fomite transmission. Ten households with ≥1 person with laboratory-confirmed COVID-19 and with ≥2 members total were enrolled in Utah, U.S.A. Nasopharyngeal and anterior nasal swabs were collected from members and tested for the presence of SARS-CoV-2 by RT-PCR. Fifteen surfaces were sampled in each household and tested for presence and viability of SARS-CoV-2. SARS-CoV-2 RNA was detected in 23 (15%) of 150 environmental swab samples, most frequently on nightstands (4/6; 67%), pillows (4/23; 17%), and light switches (3/21; 14%). Viable SARS-CoV-2 was cultured from one sample. All households with SARS-CoV-2-positive surfaces had ≥1 person who first tested positive for SARS-CoV-2 ≤ 6 days prior to environmental sampling. SARS-CoV-2 surface contamination occurred early in the course of infection when respiratory transmission is most likely, notably on surfaces in close, prolonged contact with persons with COVID-19. While fomite transmission might be possible, risk is low.
Journal Article
Community-Based Dreaming: Imagination in the Body
This research study explored the lived experience of participants in a group based on the author’s community-healing dreamwork model, a process of engaging the imagination in the embodiment of dream symbols and images with the aim of furthering the individuation of the participants and the collective. The research was conducted from a somatic perspective informed by depth psychology for the purpose of acquiring a new clinical understanding of the role of communal dreaming in somatic and depth counseling and education practice. The author used a participatory leadership approach with the group, which met weekly for 6 months, exploring one of the participant’s dream each week using active imagination in the movement and amplification of dream symbols and content. An emphasis on community healing techniques and embodiment provided a multifaceted experience including a somatic aspect. Utilizing phenomenological and alchemical hermeneutic methodologies, the author examined the community dream process and the somatic experiences of the participants’ communal embodiment of dream images. This exploration demonstrates new methods for moving imagination into the body by focusing on (a) moments of the lived experience of embodiment connected to a dream image, a felt sense, and feeling; (b) the frustrated state of individuals struggling with the pervasive conditioning of rational modes of relating to psychic content; (c) an archetypal ritual that shifts rational modes into embodied process; and (d) the possibility of respectful community conflict to engage deep layers of affect toward individuation.
Dissertation
An Exploratory Study of Healthcare Recommendations for Overcoming Reservations Towards Telemedicine Held by Medical Providers
Telemedicine is a form of medicine that allows a patient to be seen in a face-to-face environment without actual physical contact. Delivery of healthcare through telemedicine is changing the face of healthcare delivery models and allowing for improved quality, affordability of care through low to no out-of-pocket expense to the patients and making healthcare available equally to all. The problem addressed in the study was the real and perceived barriers that medical and mental health providers feel exist in delivering quality healthcare through telemedicine and how health care managers can help overcome these barriers to deliver better more reliable care. The method used in the study was a qualitative study with the use of a questionnaire. As the study reviewed, some preconceived barriers are lack of internet, not having physical contact for routine follow-ups, and patients not being receptive to the care delivery method. A main takeaway from the study revealed that education is the key to successfully helping providers better understand the use and advantages of telemedicine.
Dissertation
Supporting Family Choice
Supporting family choice in the decision-making process is recommended practice in the field of early childhood and early childhood special education. These decisions may relate to the medical, educational, social, recreational, therapeutic/rehabilitative, and community aspects of the child's disability. Although this practice conveys the message that families are the primary decision-makers for their children, families are not always adequately supported by professionals through the decision-making process. This manuscript calls for a renewed focus on family choice from the parents' perspective by offering vignettes from parents who have had both positive and negative experiences with parent choice. To explore family choice, this manuscript includes discussions of (a) ethical, societal, and legislative rationales for families making choices, (b) benefits and challenges of family informed choice in practice, and (c) clarification of the professionals' roles. This manuscript provides recommendations and strategies for assisting professionals in facilitating and optimizing the choice process for families.
Journal Article