Programmed Death Ligand 2 in Cancer-Induced Immune Suppression

Inhibitory molecules of the B7/CD28 family play a key role in the induction of immune tolerance in the tumor microenvironment. The programmed death-1 receptor (PD-1), with its ligands PD-L1 and PD-L2, constitutes an important member of these inhibitory pathways. The relevance of the PD-1/PD-L1 pathway in cancer has been extensively studied and therapeutic approaches targeting PD-1 and PD-L1 have been developed and are undergoing human clinical testing. However, PD-L2 has not received as much attention and its role in modulating tumor immunity is less clear. Here, we review the literature on the immunobiology of PD-L2, particularly on its possible roles in cancer-induced immune suppression and we discuss the results of recent studies targeting PD-L2 in cancer

Semiparametric approach to characterize unique gene expression trajectories across time

BACKGROUND: A semiparametric approach was used to identify groups of cDNAs and genes with distinct expression profiles across time and overcome the limitations of clustering to identify groups. The semiparametric approach allows the generalization of mixtures of distributions while making no specific parametric assumptions about the distribution of the hidden heterogeneity of the cDNAs. The semiparametric approach was applied to study gene expression in the brains of Apis mellifera ligustica honey bees raised in two colonies (A. m. mellifera and ligustica) with consistent patterns across five maturation ages. RESULTS: The semiparametric approach provided unambiguous criteria to detect groups of genes, trajectories and probability of gene membership to groups. The semiparametric results were cross-validated in both colony data sets. Gene Ontology analysis enhanced by genome annotation helped to confirm the semiparametric results and revealed that most genes with similar or related neurobiological function were assigned to the same group or groups with similar trajectories. Ten groups of genes were identified and nine groups had highly similar trajectories in both data sets. Differences in the trajectory of the reminder group were consistent with reports of accelerated maturation in ligustica colonies compared to mellifera colonies. CONCLUSION: The combination of microarray technology, genomic information and semiparametric analysis provided insights into the genomic plasticity and gene networks linked to behavioral maturation in the honey bee

Revs. Bruce L. Nicholas, Jack King, C.L. Potts, W.L. Robinson to Mr. Meredith (9 October 1962)

https://egrove.olemiss.edu/mercorr_pro/2092/thumbnail.jp

Pleural Fluid Mesothelin as an Adjunct to the Diagnosis of Pleural Malignant Mesothelioma

Rationale:. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives:. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results:. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions:. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis

Auto-Antibodies to β-F1-ATPase and Vimentin in Malignant Mesothelioma

Patients with Malignant Mesothelioma (MM) develop unidentified auto-antibodies to MM tumour antigens. This study was conducted to identify the targets of MM patient auto-antibodies in order to try to understand more of the anti-tumour response and to determine if these antibodies might be helpful for diagnosis or prognostication. Using MM patient sera in a Western immunoblott screening strategy, no common immunoreactive proteins were identified. The sera from one long-term survivor recognised a protein band of 50–60 kDa present in cell lysates from four of five MM cell lines tested. The immunoreactive proteins in this band were identified by 2D electrophoretic separation of a MM cell line protein lysate, followed by analysis of excised immunoreactive proteins on a MALDI TOF mass spectrometer and peptide mass fingerprinting. The immunoreactive proteins identified were vimentin (accession gi55977767) and the ATP synthase (F1-ATPase) beta chain (accession gi114549 and gi47606749). ELISA assays were developed for antibodies to these proteins. Neither vimentin (median and 95% CI 0.346; 0.32–0.468 for MM patients, 0.327; 0.308–0.428 for controls) nor ß-F1-ATPase (0.257; 0.221–0.453 for MM patients, 0.263; 0.22–0.35 for controls) showed significant differences in autoantibody levels between a group of MM patients and controls. Using a dichotomized antibody level (high, low) for these targets we demonstrated that vimentin antibody levels were not associated with survival. In contrast, high ß-F1-ATPase antibody levels were significantly associated with increased median survival (18 months) compared to low ß F1 ATPase antibody levels (9 months; p = 0.049). Immunohistochemical analysis on a MM tissue microarray showed cytoplasmic staining in 28 of 33 samples for vimentin and strong cytoplasmic staining in14 and weak in 16 samples for ß-F1-ATPase. Therefore antibodies to neither vimentin nor ß-F1-ATPase are useful for differential diagnosis of MM, however high antibody levels to ß-F1-ATPase may be associated with increased survival and this warrants further investigation

Developmental activation of the lysozyme gene in chicken macrophage cells is linked to core histone acetylation at its enhancer elements

Native chromatin IP assays were used to define changes in core histone acetylation at the lysozyme locus during developmental maturation of chicken macrophages and stimulation to high-level expression by lipo-polysaccharide. In pluripotent precursors the lysozyme gene (Lys) is inactive and there is no acetylation of core histones at the gene, its promoter or at the upstream cis-control elements. In myeloblasts, where there is a very low level of Lys expression, H4 acetylation appears at the cis-control elements but not at the Lys gene or its promoter: neither H3 nor H2B become significantly acetylated in myeloblasts. In mature macrophages, Lys expression increases 5-fold: H4, H2B and H2A.Z are all acetylated at the cis-control elements but H3 remains unacetylated except at the −2.4 S silencer. Stimulation with LPS increases Lys expression a further 10-fold: this is accompanied by a rise in H3 acetylation throughout the cis-control elements; H4 and H2B acetylation remain substantial but acetylation at the Lys gene and its promoter remains low. Acetylation is thus concentrated at the cis-control elements, not at the Lys gene or its immediate promoter. H4 acetylation precedes H3 acetylation during development and H3 acetylation is most directly linked to high-level Lys expression

Developmental activation of the lysozyme gene in chicken macrophage cells is linked to core histone acetylation at its enhancer elements

Native chromatin IP assays were used to define changes in core histone acetylation at the lysozyme locus during developmental maturation of chicken macrophages and stimulation to high-level expression by lipo-polysaccharide. In pluripotent precursors the lysozyme gene (Lys) is inactive and there is no acetylation of core histones at the gene, its promoter or at the upstream cis-control elements. In myeloblasts, where there is a very low level of Lys expression, H4 acetylation appears at the cis-control elements but not at the Lys gene or its promoter: neither H3 nor H2B become significantly acetylated in myeloblasts. In mature macrophages, Lys expression increases 5-fold: H4, H2B and H2A.Z are all acetylated at the cis-control elements but H3 remains unacetylated except at the −2.4 S silencer. Stimulation with LPS increases Lys expression a further 10-fold: this is accompanied by a rise in H3 acetylation throughout the cis-control elements; H4 and H2B acetylation remain substantial but acetylation at the Lys gene and its promoter remains low. Acetylation is thus concentrated at the cis-control elements, not at the Lys gene or its immediate promoter. H4 acetylation precedes H3 acetylation during development and H3 acetylation is most directly linked to high-level Lys expression

Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy

Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we determined incidence, prevalence, and outcomes among hemodialysis patients with atrial fibrillation. Cox proportional hazards models, to identify associations with newly diagnosed atrial fibrillation and clinical outcomes, were stratified by country and study phase and adjusted for descriptive characteristics and comorbidities. Of 17,513 randomly sampled patients, 2188 had preexisting atrial fibrillation, with wide variation in prevalence across countries. Advanced age, non-black race, higher facility mean dialysate calcium, prosthetic heart valves, and valvular heart disease were associated with higher risk of new atrial fibrillation. Atrial fibrillation at study enrollment was positively associated with all-cause mortality and stroke. The CHADS2 score identified approximately equal-size groups of hemodialysis patients with atrial fibrillation with low (less than 2) and higher risk (more than 4) for subsequent strokes on a per 100 patient-year basis. Among patients with atrial fibrillation, warfarin use was associated with a significantly higher stroke risk, particularly in those over 75 years of age. Our study shows that atrial fibrillation is common and associated with elevated risk of adverse clinical outcomes, and this risk is even higher among elderly patients prescribed warfarin. The effectiveness and safety of warfarin in hemodialysis patients require additional investigation

Greater Sage-Grouse movements and habitat use during winter in central Oregon

Greater Sage-Grouse (Centrocercus urophasianus) depend on sagebrush habitat for food and cover during winter, yet few sage-grouse winter ecology studies have been conducted. During January and February 2007, we monitored 22 radio-collared sage-grouse (7 females and 15 males) in central Oregon to characterize winter habitat use and movement patterns. We estimated distances traveled between locations on a weekly basis and quantified habitat characteristics at locations used by male and female sage-grouse. The birds we collared moved extensively across the landscape, using approximately 1480 km². Sagebrush canopy height in sites used by sage-grouse varied from 0.25 to 0.75 m, with females tending to be found in sites with taller sagebrush and less foliar cover than in sites where we found males. The difference in foliar cover between sexes was related to a seasonal change in habitat use: 4 females found in little sagebrush (Artemisia arbuscula) in January and early February were no longer located nor found foraging in little sagebrush after 15 February. Also, by this date, most male sage-grouse had stopped using big sagebrush (Artemisia tridentata) as they migrated to leks. Sage-grouse mortality rates were low during our study, which may be attributed to the study area receiving half the long-term average amount of snow. The large area over which sage-grouse moved during winter indicates that conservation of Greater Sage-Grouse may require preservation of sagebrush at landscape scales (thousands of square kilometers).KEYWORDS: Sage-Grouse, Oregon, Habitat, Centrocercus urophasianusThis is the publisher’s final pdf. The published article is copyrighted by Brigham Young University and can be found at: https://ojs.lib.byu.edu/ojs/index.php/wna