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Shifting the meaning of democracy : race, politics, and culture in the United States and Brazil
\"This book offers a historical analysis of one of the most striking and dramatic transformations to take place in Brazil and the United States during the twentieth century--the redefinition of the concepts of nation and democracy in racial terms. The multilateral political debates that occurred between 1930 and 1945 pushed and pulled both states towards more racially inclusive political ideals and nationalisms. Both countries utilized cultural production to transmit these racial political messages. At times working collaboratively, Brazilian and U.S. officials deployed the concept of \"racial democracy\" as a national security strategy, one meant to suppress the existential threats perceived to be posed by World War II and by the political agendas of communists, fascists, and blacks. Consequently, official racial democracy was limited in its ability to address racial inequities in the United States and Brazil. Shifting the Meaning of Democracy helps to explain the historical roots of a contemporary phenomenon: the coexistence of widespread antiracist ideals with enduring racial inequality\"--Provided by publisher.
Book
Use of Cell-SELEX to Generate DNA Aptamers as Molecular Probes of HPV-Associated Cervical Cancer Cells
Disease-specific biomarkers are an important tool for the timely and effective management of pathological conditions, including determination of susceptibility, diagnosis, and monitoring efficacy of preventive or therapeutic strategies. Aptamers, comprising single-stranded or double-stranded DNA or RNA, can serve as biomarkers of disease or biological states. Aptamers can bind to specific epitopes on macromolecules by virtue of their three dimensional structures and, much like antibodies, aptamers can be used to target specific epitopes on the basis of their molecular shape. The Systematic Evolution of Ligands by EXponential enrichment (SELEX) is the approach used to select high affinity aptamers for specific macromolecular targets from among the >10(13) oligomers comprising typical random oligomer libraries. In the present study, we used live cell-based SELEX to identify DNA aptamers which recognize cell surface differences between HPV-transformed cervical carcinoma cancer cells and isogenic, nontumorigenic, revertant cell lines.
Whole-cell SELEX methodology was adapted for use with adherent cell lines (which we termed Adherent Cell-SELEX (AC-SELEX)). Using this approach, we identified high affinity aptamers (nanomolar range K(d)) to epitopes specific to the cell surface of two nontumorigenic, nontumorigenic revertants derived from the human cervical cancer HeLa cell line, and demonstrated the loss of these epitopes in another human papillomavirus transformed cervical cancer cell line (SiHa). We also performed preliminary investigation of the aptamer epitopes and their binding characteristics.
Using AC-SELEX we have generated several aptamers that have high affinity and specificity to the nontumorigenic, revertant of HPV-transformed cervical cancer cells. These aptamers can be used to identify new biomarkers that are related to carcinogenesis. Panels of aptamers, such as these may be useful in predicting the tumorigenic potential and properties of cancer biopsies and aid in the effective management of pathological conditions (diagnosis, predicted outcome, and treatment options).
Journal Article
Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.
Journal Article
A Mouse Model of Chronic West Nile Virus Disease
Infection with West Nile virus (WNV) leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013)F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.
Journal Article
The Buffering Effects of Emotion Regulation in the Relationship Between Experiences of Racism and Anxiety in a Black American Sample
The current study explores the potential moderating effect of difficulties in emotion regulation on the relationship between racist experiences and anxiety symptomology in a Black American sample. One hundred forty participants completed a questionnaire packet containing measures of anxious arousal and stress (general anxiety) symptoms, difficulties in emotion regulation, and experiences of racist events. Results indicated that difficulties in emotion regulation moderated the relationship between past week frequency of racist events and anxious arousal as well as past year frequency of racist events and anxious arousal. Specifically, these relationships were significantly positive at high levels of difficulties in emotion regulation and not significant at low levels of difficulties in emotion regulation. Emotion regulation skills may help Black Americans cope with anxious arousal related to racist experiences. The clinical implications of these findings and future research directions are discussed.
Journal Article
Memory T cells possess an innate-like function in local protection from mucosal infection
Mucosal infections pose a significant global health burden. Antigen-specific tissue-resident T cells are critical to maintaining barrier immunity. Previous studies in the context of systemic infection suggest that memory CD8+ T cells may also provide innate-like protection against antigenically unrelated pathogens independent of T cell receptor engagement. Whether bystander T cell activation is also an important defense mechanism in the mucosa is poorly understood. Here, we investigated whether innate-like memory CD8+ T cells could protect against a model mucosal virus infection, herpes simplex virus 2 (HSV-2). We found that immunization with an irrelevant antigen delayed disease progression from lethal HSV-2 challenge, suggesting that memory CD8+ T cells may mediate protection despite the lack of antigen specificity. Upon HSV-2 infection, we observed an early infiltration, rather than substantial local proliferation, of antigen-nonspecific CD8+ T cells, which became bystander-activated only within the infected mucosal tissue. Critically, we show that bystander-activated CD8+ T cells are sufficient to reduce early viral burden after HSV-2 infection. Finally, local cytokine cues within the tissue microenvironment after infection were sufficient for bystander activation of mucosal tissue memory CD8+ T cells from mice and humans. Altogether, our findings suggest that local bystander activation of CD8+ memory T cells contributes a fast and effective innate-like response to infection in mucosal tissue.
Journal Article
Decentering as a Common Link among Mindfulness, Cognitive Reappraisal, and Social Anxiety
Background: The tendency to employ both cognitive reappraisal and mindfulness are associated with reduced trait social anxiety; however, it is unclear whether reappraisal and mindfulness are associated with social anxiety through the same mechanisms. It has been proposed that decentering, or the process of seeing thoughts or feelings as objective events in the mind rather than personally identifying with them, may be a key mechanism underlying both cognitive reappraisal and mindfulness. Aims: To examine the relationships between reappraisal, mindfulness, decentering, and social anxiety. Method: This study utilized structural equation modeling to examine the relationships among cognitive reappraisal, mindfulness, decentering, and social anxiety in a large cross-sectional study. Results: Results indicate that the relationship between mindfulness and social anxiety is partially accounted for by decentering, whereas the relationship between cognitive reappraisal and social anxiety is more fully accounted for by decentering. Conclusions: These results imply that decentering may be a common mechanism underlying both cognitive reappraisal and mindfulness, although mindfulness may also affect social anxiety through additional mechanisms. However, given the cross-sectional nature of these findings, results should be considered preliminary, with future research being needed to further elucidate these relationships.
Journal Article
Bacterial vaginosis associates with dysfunctional T cells and altered soluble immune factors in the cervicovaginal tract
BACKGROUNDBacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually acquired HIV, yet the immunological mechanisms underlying this association are not well understood.METHODSTo investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, Kinga Study participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples.RESULTSHigh-parameter flow cytometry revealed an increased frequency of cervical CD4+ conventional T (Tconv) cells expressing CCR5 in BR+ versus BR- women. However, we found no difference in the number of CD3+CD4+CCR5+ cells in the CX or VT of BV+ versus BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV had an increased frequency of dysfunctional CX and VT CD39+ Tconv and CX tissue-resident CD69+CD103+ Tconv cells, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations.CONCLUSIONOur comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV, including increased HIV susceptibility.TRIAL REGISTRATIONClinicalTrials.gov NCT03701802.FUNDINGThis work was supported by National Institutes of Health grants R01AI131914, R01AI141435, and R01AI129715.
Journal Article