Exploring and contextualizing the associations among political identification, vaccine risk and benefit perceptions, and vaccine acceptance.

There is considerable research on the influence of political partisanship on vaccine acceptance. However, the current study is one of the first to investigate how political identification is related to risk and benefit perceptions vis-à-vis vaccines. Based on survey data collected in the United States regarding four different vaccines at three points in time (n = 383 for April-June 2012; n = 364 for March 2020; n = 334 for April-May 2020), Democrats were found to have more positive attitudes toward vaccinations in general and hold more favorable risk and benefit perceptions of pandemic and routine vaccines overall compared to Republicans. However, the onset of a pandemic can serve as an equalizing force and motivate similar risk and benefit perceptions across party lines, but this force can wane quickly when the information environment is politicized. For political partisans who are ideologically oriented to be more hesitant toward vaccines, two conditions can help sustain their favorable vaccine perceptions during a pandemic: (a) when they identify with the governing political party, and (b) when there are consistent reassurances of vaccine safety and effectiveness from their partisan leadership. Given that risk and benefit perceptions were found to be consistently associated with vaccine acceptance across contexts in this study, communication aimed at encouraging vaccinations should always address the risks and benefits of a vaccine in ways that are tailored for individuals with different political affiliations.

Do cognition and emotion matter? A study of COVID-19 vaccination decision-making in college students.

The unparalleled speed of COVID-19 vaccine development has necessitated an expansion of existing knowledge on vaccination decision-making. The current study explored (1) how cognitions and emotions shaped college students' COVID-19 vaccination decisions, and (2) where vaccination-inclined and vaccination-hesitant students converged and diverged in their decision-making process. Seventy-seven students participated in 26 focus groups to discuss their complex thoughts and feelings regarding COVID-19 vaccination, offering a more nuanced understanding of COVID-19 vaccination decision-making that has not been fully captured by quantitative studies. Thematic analysis found that vaccination-inclined participants and their hesitant counterparts reported differential patterns of positive and negative emotions, systematic appraisals, and heuristics in decision-making. Future research should investigate the roles of hope and relief, non-health-related benefits of vaccination, social trust, and interpersonal influence in vaccination decision-making.

Distinct effects of ruxolitinib and interferon-alpha on murine JAK2V617F myeloproliferative neoplasm hematopoietic stem cell populations.

JAK2V617F is the most common mutation in patients with BCR-ABL negative myeloproliferative neoplasms (MPNs). The eradication of JAK2V617F hematopoietic stem cells (HSCs) is critical for achieving molecular remissions and cure. We investigate the distinct effects of two therapies, ruxolitinib (JAK1/2 inhibitor) and interferon-alpha (IFN-α), on the disease-initiating HSC population. Whereas ruxolitinib inhibits Stat5 activation in erythroid progenitor populations, it fails to inhibit this same pathway in HSCs. In contrast, IFN-α has direct effects on HSCs. Furthermore, STAT1 phosphorylation and pathway activation is greater after IFN-α stimulation in Jak2V617F murine HSCs with increased induction of reactive oxygen species, DNA damage and reduction in quiescence after chronic IFN-α treatment. Interestingly, ruxolitinib does not block IFN-α induced reactive oxygen species and DNA damage in Jak2V617F murine HSCs in vivo. This work provides a mechanistic rationale informing how pegylated IFN-α reduces JAK2V617F allelic burden in the clinical setting and may inform future clinical efforts to combine ruxolitinib with pegylated IFN-α in patients with MPN.

Predicting Vaccination Intention and Benefit and Risk Perceptions: The Incorporation of Affect, Trust, and Television Influence in a Dual-Mode Model.

Major health behavior change models tend to consider health decisions as primarily resulting from a systematic appraisal of relevant beliefs, such as the perceived benefits and risks of a pharmacological intervention. Drawing on research from the disciplines of risk management, communication, and psychology, this study proposed the inclusion of a heuristic route in established theory and tested the direction of influence between heuristic and systematic process variables. Affect and social trust were included as key heuristics in the proposed dual-mode framework of health decision making. Furthermore, exposure to health-related coverage on television was considered potentially influential over both heuristic and systematic process variables. To test this framework, data were collected from a national probability sample of 584 adults in the United States in 2012 regarding their decision to vaccinate against a hypothetical avian flu. The results provided some support for the bidirectional influence between heuristic and systematic processing. Affect toward flu vaccination and trust in the Food and Drug Administration were found to be powerful predictors of vaccination intention, enhancing intention both directly and indirectly via certain systematic process variables. The direction of influence between perceived susceptibility and severity, on the one hand, and affect, on the other, is less clear, suggesting the need for further research. Contrary to the opinion of media critics, exposure to televised health coverage was negatively associated with the perceived risks of vaccination. Results from this study carry theoretical and practical implications, and applying this model to the acceptance of different health interventions constitutes an area for future inquiries.

Phylogenetic analysis, expression patterns, and transcriptional regulation of human CTEN gene.

Cten is a focal adhesion molecule and a member of the tensin family. Its expression is highly enriched in the prostate and placenta, suggesting that cten gene might be closely associated with mammalian species. Recent studies have reported that cten expression is frequently up-regulated in a variety of cancers and its levels appear to correlate with tumorigenicity. Here, we have (1) analyzed cten sequences of various species to build a phylogenetic tree, (2) examined cten mRNA levels in human and mouse tissues to establish its expression profiles, and (3) determined the promoter region of human CTEN gene in cell lines and in a mouse model to understand its transcriptional regulation. Our analyses indicate that all currently known cten genes are present in mammals. The prostate and placenta are the two most cten abundant tissues in human and mouse, meanwhile brain and lung also express low levels of cten. Results from cell culture reporter assays demonstrate that a 327-bp fragment is the shortest functional promoter. All functional promoter constructs produce 40- to 160-fold increases in luciferase reporter activities in normal prostate cells, whereas lower activities (<40-fold) are detected in non-prostatic cell lines. To evaluate CTEN promoter activity in mice and develop a new tissue specific Cre recombinase mouse model, we have established pCTEN-Cre:R26R mice by crossing R26R ß-galactosidase reporter mice with pCTEN-Cre transgenic mice, in which the 327-bp cten promoter drives the expression of Cre recombinase. X-gal analysis has shown strong ß-galactosidase activities in the prostate, brain, and few other tissues in pCTEN-Cre:R26R mice. Altogether, we have identified the promoter region of human cten gene and provided a useful tool for investigating cell lineages and generating tissue-specific knockout or knockin mice.

Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors.

There is overwhelming evidence that tyrosine kinases play an important role in cancer development. As a prototype of targeted therapy, tyrosine kinase inhibitors are now successfully applied to cancer treatment. However, as single agents, tyrosine kinase inhibitors have not achieved satisfactory results in the treatment of prostate cancer, principally due to their inability to efficiently kill tumor cells. The authors' laboratory has been interested in the role of the Src complex in prostate cancer progression, including the induction of androgen independence and metastasis. Previously, the authors reported that Src inhibitors such as saracatinib and PP2 caused G1 growth arrest and diminished invasiveness in prostate cancer cells but rarely apoptosis. Here, they have shown that Src family kinase (SFK) inhibitors can induce a high level of autophagy, which protects treated cells from undergoing apoptosis. Src siRNA knockdown experiments confirmed that autophagy was indeed caused by the lack of Src activity. The SFK inhibitor-induced autophagy is accompanied by the inhibition of the PI3K (type I)/Akt/mTOR signaling pathway. To test whether autophagy blockade could lead to enhanced cell death, pharmacological inhibitors (3-methyladenine and chloroquine) and a genetic inhibitor (siRNA targeting Atg7) were used in combination with SFK inhibitors. The results showed that autophagy inhibition effectively enhanced cell killing induced by SFK inhibitors. Importantly, the authors showed that a combination of saracatinib with chloroquine in mice significantly reduced prostate cancer (PC3) xenograft growth compared with the control group. Taken together, these data suggest that (1) autophagy serves a protective role in SFK inhibitor-mediated cell killing, and (2) clinically acceptable autophagy modulators may be used beneficially as adjunctive therapeutic agents for SFK inhibitors.

Up-regulation of C-terminal tensin-like molecule promotes the tumorigenicity of colon cancer through beta-catenin.

C-terminal tensin-like (cten) is a focal adhesion molecule belonging to the tensin family. Previous studies have suggested that cten may function as a prostate-specific tumor suppressor. Here, we show that although cten is expressed at a very low level in normal colon, its expression is significantly up-regulated in colon cancer. Furthermore, a high population of cten is found in the nucleus, where it interacts with beta-catenin, a critical player in the canonical Wnt pathway. This interaction may contribute to the role of cten in enhancing the colony formation, anchorage-independent growth, and invasiveness of colon cancer cells. Our studies have identified cten as a novel nuclear partner of beta-catenin, showed an oncogenic activity of cten in colon cancers, and revealed cten as a potential biomarker and target for colon cancers.

Conditional loss of PTEN leads to skeletal abnormalities and lipoma formation.

To understand the role of tumor suppressor PTEN in cartilage development, we have generated chondrocyte specific PTEN deletion mice using Col2a1Cre and PTEN(loxp/loxp) mice. PTEN mutant mice are viable and fertile, nonetheless, develop kyphosis over time. Histological analyses show mutant vertebrae and intervertebral discs are larger and therefore the spines are longer than in control mice. In addition, the growth plates are thicker, invading trabecular bone areas are deeper, and marrow adipocyte populations are higher in PTEN mutant mice. Furthermore, the growth plates, not normally fused in mouse long bones, are fused in PTEN mutants. Intriguingly, PTEN mice develop lipomas and show abnormal accumulation of fat tissues along spines. Cell tracking assays have confirmed that lipomas and a portion of fat tissues were derived from Col2a1Cre PTEN(loxp/loxp) cells. Further analyses have suggested that the phenotypes of PTEN mutant likely attribute to PTEN's negatively regulating role in PI3K/Akt pathway.

The N-terminal half of talin2 is sufficient for mouse development and survival.

Using a talin2 gene-trapped embryonic stem cell clone, we have developed a talin2 mutant mouse line that expresses the N-terminal half (1-1295) of talin2 fused with beta-galactosidase. The homozygous mutant mice appear to be normal and healthy. In the testis, talin2 expresses as a shorter form with a unique 30 residues at N-terminus linking to a common C-terminus from 1122 to 2453 of the long form. The resulting talin2 in the mutant testis only contains 204 residues of the wild-type testis talin2. However, it did not seem to affect the morphology of testis or reproduction of male mice. In fact, male and female mutant mice are fertile. Utilizing the expression of talin2(1-1295)/beta-galactosidase fusion protein, we have examined the distribution of talin2 in tissues. In contrast to talin1, talin2 expression is more restricted in tissues and cell types.