Life Sciences Commons^™

Prevalence And Prognostic Role Of Triple-Negative Breast Cancer By Race: A Surveillance Study, Helen Swede, David I. Gregorio, Susan H. Tannenbaum, Jessica A. Brockmeyer, Lori L. Wilson, Mellisa A. Pensa, Richard G. Stevens, Carolyn D. Runowicz

UCHC Articles - Research

A possible explanation for the relatively poor survival from breast cancer among blacks is the much higher rate of the adverse Triple-Negative sub-type. In a study of 1372 patients, blacks had twice the risk of death compared to whites among those with advanced cancer whether or not tumors were Triple-Negative. More research is still warranted to determine why blacks with advanced, but not local, breast cancer have a consistently higher rate of death.

Introduction

Emerging research suggests a substantially greater prevalence of the adverse triple-negative (TN) subtype (human epidermal growth factor receptor [HER]2⁻, estrogen receptor [ER]⁻, …

The Branched Actin Nucleator Arp2/3 Promotes Nuclear Migrations And Cell Polarity In The C. Elegans Zygote, William A. Mohler

UCHC Articles - Research

Regulated movements of the nucleus are essential during zygote formation, cell migrations, and differentiation of neurons. The nucleus moves along microtubules (MTs) and is repositioned on F-actin at the cellular cortex. Two families of nuclear envelope proteins, SUN and KASH, link the nucleus to the actin and MT cytoskeletons during nuclear movements. However, the role of actin nucleators in nuclear migration and positioning is poorly understood. We show that the branched actin nucleator, Arp2/3, affects nuclear movements throughout embryonic and larval development in C. elegans, including nuclear migrations in epidermal cells and neuronal precursors. In one-cell embryos the migration …

Division Of Labor Between Subsets Of Lymph Node Dendritic Cells Determines The Specificity Of The Cd8 Recall Response To Influenza Infection, Jenny E. Suárez-Ramírez, Tao Wu, Young-Tae Lee, Carolina C. Aguila, Keith R. Bouchard, Linda Linda Cauley

UCHC Articles - Research

Cytotoxic T lymphocytes are important targets for vaccines against a wide variety of infections that enter the body via mucosal tissues. To induce effective immunity these vaccines must include the most protective epitopes and elicit rapid recall responses at the site of infection. Although live attenuated viruses are sometimes used to induce cellular immunity against recurrent influenza infections, the mechanisms that determine the magnitude of the response to individual viral components are very poorly defined. Heterosubtypic infections in B6 mice illustrate an additional level of complexity, when the antigen-specificity of the response shifts dramatically between primary and secondary challenge. This …

T Cells Expanded In Presence Of Il-15 Exhibit Increased Antioxidant Capacity And Innate Effector Molecules, Nitya G. Chakraborty, Bijay Mukherji

UCHC Articles - Research

Persistence of effector cytotoxic T lymphocytes (CTLs) during an immunological response is critical for successfully controlling a viral infection or tumor growth. Various cytokines are known to play an important part in regulating the immune response. The IL-2 family of cytokines that includes IL-2 and IL-15 are known to function as growth and survival factors for antigen-experienced T cells. IL-2 and IL-15 possess similar properties, including the ability to induce T cell proliferation. Whereas long term IL-2 exposure has been shown to promote apoptosis and limit CD8⁺ memory T cell survival and proliferation, it is widely believed that IL-15 …

Loss Of Dna Mismatch Repair Imparts A Selective Advantage In Planarian Adult Stem Cells, Jessica P. Hollenbach, Alissa M. Resch, Dasaradhi Palakodeti, Brenton R. Graveley, Christopher D. Heinen

UCHC Articles - Research

Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, …

Mekk3 Regulates Ifn-Γ Production In T Cells Through The Rac1/2-Dependent Mapk Cascades, Xiaofang Wang

UCHC Articles - Research

MEKK3 is a conserved Ser/Thr protein kinase belonging to the MAPK kinase kinase (MAP3K) family. MEKK3 is constitutively expressed in T cells, but its function in T cell immunity has not been fully elucidated. Using Mekk3 T cell conditional knockout (T-cKO) mice, we show that MEKK3 is required for T cell immunity in vivo. Mekk3 T-cKO mice had reduced T cell response to bacterial infection and were defective in clearing bacterial infections. The Ag-induced cytokine production, especially IFN-γ production, was impaired in Mekk3-deficient CD4 T cells. The TCR-induced ERK1/2, JNK, and p38 MAPKs activation was also defective in Mekk3 …

Generation And Characterization Of Col10a1 -Mcherry Reporter Mice, Peter Maye, Yu Fu, Yaling Liu, Mary Louise Stover, Xi Jiang, David W. Rowe

UCHC Articles - Research

We report here on the generation of a new fluorescent protein reporter transgenic mouse line, Col10a1 -mCherry, which can be used as a tool to study chondrocyte biology and pathology. Collagen, Type X, alpha 1(Col10a1) is highly expressed in hypertrophic chondrocytes and commonly used as a gene marker for this cell population. TheCol10a1-mCherry reporter line was generated using a bacterial recombination strategy with the mouse BAC clone RP23-192A7. To aid in the characterization of this animal model, we intercrossed Col10a1-mCherry mice with Collagen, Type II, alpha 1 (Col2a1) enhanced cyan fluorescent protein (ECFP) reporter mice and characterized the expression of …

Tumor Recognition And Self-Recognition Induce Distinct Transcriptional Profiles In Antigen-Specific Cd4 T Cells, Adam J. Adler

UCHC Articles - Research

Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA × TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HA^high), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HA^high resulted in a functionally inactivated …

Phagosomal Signaling By Borrelia Burgdorferi In Human Monocytes Involves Toll-Like Receptor (Tlr) 2 And Tlr8 Cooperativity And Tlr8-Mediated Induction Of Ifn-Β, Jorge L. Cervantes, Star M. Dunham-Ems, Carson J. La Vake, Mary M. Petzke, Justin D. Radolf, Juan C. Salazar

UCHC Articles - Research

Phagocytosed Borrelia burgdorferi (Bb) induces inflammatory signals that differ both quantitatively and qualitatively from those generated by spirochetal lipoproteins interacting with Toll-like receptor (TLR) 1/2 on the surface of human monocytes. Of particular significance, and in contrast to lipoproteins, internalized spirochetes induce transcription of IFN-β. Using inhibitory immunoregulatory DNA sequences (IRSs) specific to TLR7, TLR8, and TLR9, we show that the TLR8 inhibitor IRS957 significantly diminishes production of TNF-α, IL-6, and IL-10 and completely abrogates transcription of IFN-β in Bb-stimulated monocytes. We demonstrate that live Bb induces transcription of TLR2 and TLR8, whereas IRS957 interferes with their transcriptional regulation. Using …

Kalrn Promoter Usage And Isoform Expression Respond To Chronic Cocaine Exposure, Richard E. Mains, Drew D. Kiraly, Jodi E. Eipper-Mains, Xin-Ming Ma, Betty A. Eipper

UCHC Articles - Research

Background The long-term effects of cocaine on behavior are accompanied by structural changes in excitatory glutamatergic synapses onto the medium spiny neurons of the striatum. The Kalrn gene encodes several functionally distinct isoforms; these multidomain guanine nucleotide exchange factors (GEFs) contain additional domains known to interact with phosphatidylinositides as well as with a number of different proteins. Through their activation of Rho proteins and their interactions with other proteins, the different Kalirin isoforms affect cytoskeletal organization. Chronic exposure of adult male rodents to cocaine increases levels of Kalirin 7 in the striatum. When exposed chronically to cocaine, mice lacking Kalirin …

Imaging—And Imagining—Immune Responses To Infections, Kamal M. Khanna, Leo Lefrancois

UCHC Articles - Research

The use of sophisticated microscopy continues apace in analysis of infection and the induction of immune responses. Continued technological improvements in microscopy, fluorescent dyes, and transgenic reporter systems will allow constant improvements of our view of the microbial and immunological landscape. Understanding how anatomy, cellular movement and microbial pathogenesis are linked to the outcome of the immune response will allow us to make informed decisions regarding vaccine formulations and treatments for infectious diseases and their sequelae.