The group 7 complexes [M(κ-2,6-(RPO)CHN)(CO)L][BAr] [M = Mn, R = Pr, L = THF; M = Re, R = Bu, L = vacant site] undergo solid-gas reactivity with CO to form the products of THF substitution or CO addition respectively. There is a large, local, adaptive change of [BAr] anions for M = Mn, whereas for M = Re the changes are smaller and also remote to the site of reactivity.
View Article and Find Full Text PDFBackground: Thermochemical ablation (TCA) is a minimally invasive therapy under development for hepatocellular carcinoma. TCA simultaneously delivers an acid (acetic acid, AcOH) and base (sodium hydroxide, NaOH) directly into the tumor, where the acid/base chemical reaction produces an exotherm that induces local ablation. However, AcOH and NaOH are not radiopaque, making monitoring TCA delivery difficult.
View Article and Find Full Text PDFPurpose: To evaluate the feasibility of using dual-energy computed tomography (CT) and theranostic cesium hydroxide (CsOH) for image guidance of thermochemical ablation (TCA) in a rabbit VX2 tumor model.
Materials And Methods: In vivo experiments were performed on New Zealand white rabbits, where VX2 tumor fragments (0.3 mL) were inoculated into the right and left flanks (n = 16 rabbits, 32 tumors).
Microcrystalline (∼1 μm) [Rh(CyPCHCHPCy)(norbornadiene)][S-BAr], [S-BAr] = [B(3,5-(SF)CH)], reacts with H in a single-crystal to single-crystal transformation to form the σ-alkane complex [Rh(CyPCHCHPCy)(norbornane)][S-BAr], for which the structure was determined by microcrystal Electron Diffraction (microED), to 0.95 Å resolution, an on-grid hydrogenation, and a complementary single-crystal X-ray diffraction study on larger, but challenging to isolate, crystals. Comparison with the [BAr] analogue [Ar = 3,5-(CF)(CH)] shows that the [S-BAr] anion makes the σ-alkane complex robust towards decomposition both thermally and when suspended in pentane.
View Article and Find Full Text PDFCentral memory T (T) cells patrol lymph nodes and perform conventional memory responses on restimulation: proliferation, migration and differentiation into diverse T cell subsets while also self-renewing. Resident memory T (T) cells are parked within single organs, share properties with terminal effectors and contribute to rapid host protection. We observed that reactivated T cells rejoined the circulating pool.
View Article and Find Full Text PDFHepatocellular carcinoma is a growing worldwide problem with a high mortality rate. This malignancy does not respond well to chemotherapy, and most patients present late in their disease at which time surgery is no longer an option. Over the past three decades, minimally invasive methods have evolved to treat unresectable disease and prolong survival.
View Article and Find Full Text PDFPurpose: To evaluate trifluoroacetic acid (TFA) as a theranostic chemical ablation agent and determine the efficacy of TFA for both noninvasive imaging and tissue destruction.
Materials And Methods: Fluorine-19 magnetic resonance imaging (F-MRI) was optimized at 7 T using a custom-built volume coil. Fluorine images were acquired with both rapid acquisition with relaxation enhancement and balanced steady-state free precession (bSSFP) sequences with varying parameters to determine the optimal sequence for TFA.
The immune system adapts to constitutive antigens to preserve self-tolerance, which is a major barrier for anti-tumor immunity. Antigen-specific reversal of tolerance constitutes a major goal to spur therapeutic applications. Here, we show that robust, iterative, systemic stimulation targeting tissue-specific antigens in the context of acute infections reverses established CD8 T cell tolerance to self, including in T cells that survive negative selection.
View Article and Find Full Text PDFThis study examines the extent to which memory CD4 T cells share immunosurveillance strategies with CD8 resident memory T cells (T). After acute viral infection, memory CD4 T cells predominantly used residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8 T cells. In contrast, memory CD4 T cells were more likely to be resident within lymphoid organs than CD8 T cells.
View Article and Find Full Text PDFThe migratory capacity of adaptive CD8αβ T cells dictates their ability to locate target cells and exert cytotoxicity, which is the basis of immune surveillance for the containment of microbes and disease. The small intestine (SI) is the largest mucosal surface and is a primary site of pathogen entrance. Using two-photon laser scanning microscopy, we found that motility of antigen (Ag)-specific CD8αβ T cells in the SI is dynamic and varies with the environmental milieu.
View Article and Find Full Text PDFCell Stress Chaperones
March 2019
Searching the literature is often overlooked and receives inadequate attention. In this article, we seek to address this issue by presenting several strategies. Here, five steps are outlined and discussed to facilitate effective literature searching.
View Article and Find Full Text PDFUsing density functional theory (B97-D/ECP2/PCM//RI-BP86/ECP1 level), we have studied the effects of ligand variation on OH uptake by transition-metal carbonyls (Hieber base reaction), i.e., LM(CO) + OH → [LM(COH)], M = Fe, Ru, Os, L = CO, PMe, PF, py, bipy, Cl, H.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2019
Established T cell dysfunction is a barrier to antitumor responses, and checkpoint blockade presumably reverses this. Many patients fail to respond to treatment and/or develop autoimmune adverse events. The underlying reason for T cell responsiveness remains elusive.
View Article and Find Full Text PDFMany US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals.
View Article and Find Full Text PDFLymphocytes enter tissues from blood vessels through a well-characterized three-step process of extravasation. To our knowledge, nonvascular routes of lymphocyte entry have not been described. In this article, we report that Ag-experienced CD8 T cells in mice recirculate from blood through the peritoneal cavity.
View Article and Find Full Text PDFImmunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear.
View Article and Find Full Text PDFCD8 T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8 resident memory T cells (T cells) within the reproductive tracts of live female mice. We found that mucosal T cells were highly motile, but paused and underwent in situ division after local antigen challenge.
View Article and Find Full Text PDFEbola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection.
View Article and Find Full Text PDFDeveloping vaccine strategies to generate high numbers of Ag-specific CD8 T cells may be necessary for protection against recalcitrant pathogens. Heterologous prime-boost-boost immunization has been shown to result in large quantities of functional memory CD8 T cells with protective capacities and long-term stability. Completing the serial immunization steps for heterologous prime-boost-boost can be lengthy, leaving the host vulnerable for an extensive period of time during the vaccination process.
View Article and Find Full Text PDFCells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-β.
View Article and Find Full Text PDFPurpose: This article aims to review teamwork and the creation of effective teams within healthcare.
Design/methodology/approach: By combining research material found in management, psychology and health services research the article explores the drivers increasing the importance of teamwork, reviews the current knowledge base on how to build a team and focuses on some of the barriers to effective team performance.
Findings: The simultaneous inflation of healthcare costs and necessity to improve quality of care has generated a demand for novel solutions in policy, strategy, commissioning and provider organisations.
Meningococcal FetA is an iron-regulated, immunogenic outer membrane protein and vaccine component. The most diverse region of this protein is a previously defined variable region (VR) that has been shown to be immunodominant. In this analysis, a total of 275 Neisseria lactamica isolates, collected during studies of nasopharyngeal bacterial carriage in infants, were examined for the presence of a fetA gene.
View Article and Find Full Text PDFThe bacterium Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Outer membrane proteins (OMPs) are candidates in the search for comprehensive meningococcal vaccines; however, the formulation of OMP vaccines is complicated by antigenic diversity, which is generated by high levels of genetic reassortment and strong positive selection in the meningococcal antigen genes. The genetic and antigenic diversity of three OMPs (FetA, PorA, and PorB) among a global collection of meningococcal isolates representative of the major hyperinvasive clonal complexes was determined.
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