Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts.

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

Rapid Discharge After Anatomic Lung Resection: Is Ambulatory Surgery for Early Lung Cancer Possible?

BACKGROUND: Given resource constraints during the coronavirus disease 2019 pandemic, we explored whether minimally invasive anatomic lung resections for early-stage lung cancer could undergo rapid discharge. METHODS: All patients with clinical stage I-II non-small cell lung cancer from September 2019 to June 2022 who underwent minimally invasive anatomic lung resection at a single institution were included. Patients discharged without a chest tube <18 hours after operation, meeting preset criteria, were considered rapid discharge. Demographics, comorbidities, operative details, and 30-day outcomes were compared between rapid discharge patients and nonrapid discharge "control" patients. Multivariable logistic regression was performed for predictors of nonrapid discharge. RESULTS: Overall, 430 patients underwent resection (200 lobectomies and 230 segmentectomies); 162 patients (37%) underwent rapid discharge and 268 patients (63%) were controls. The rapid discharge group was younger (66.5 vs 70.0 years; P < .001), was assigned to lower American Society of Anesthesiologists class (P = .02), had more segmentectomies than lobectomies (P = .003), and had smaller tumors (P < .001). There were no differences between groups in distance from home to hospital (P = .335) or readmission rates (P = .39). Increasing age had higher odds for nonrapid discharge (odds ratio, 1.04; 95% CI, 1.02-1.07), whereas segmentectomy had decreased odds (odds ratio, 0.46; 95% CI, 0.28-0.75). CONCLUSIONS: Approximately 37% of the patients underwent rapid discharge after operation with similar readmission rate to controls. Increasing age had higher odds for nonrapid discharge; segmentectomy was likely to lead to rapid discharge. Consideration of rapid discharge minimally invasive lung resection for early-stage lung cancer can result in significant reduction in inpatient resources without adverse patient outcomes.

Tunable 1D and 2D Polyacrylonitrile Nanosheet Superstructures.

Carbon superstructures are widely applied in energy and environment-related areas. Among them, the flower-like polyacrylonitrile (PAN)-derived carbon materials have shown great promise due to their high surface area, large pore volume, and improved mass transport. In this work, we report a versatile and straightforward method for synthesizing one-dimensional (1D) nanostructured fibers and two-dimensional (2D) nanostructured thin films based on flower-like PAN chemistry by taking advantage of the nucleation and growth behavior of PAN. The resulting nanofibers and thin films exhibited distinct morphologies with intersecting PAN nanosheets, which formed through rapid nucleation on existing PAN. We further constructed a variety of hierarchical PAN superstructures based on different templates, solvents, and concentrations. These PAN nanosheet superstructures can be readily converted to carbon superstructures. As a demonstration, the nanostructured thin film exhibited a contact angle of ∼180° after surface modification with fluoroalkyl monolayers, which is attributed to high surface roughness enabled by the nanosheet assemblies. This study offers a strategy for the synthesis of nanostructured carbon materials for various applications.

Characterization of Rice Yield Based on Biomass and SPAD-Based Leaf Nitrogen for Large Genotype Plots.

The use of Unmanned Aerial Vehicle (UAV) images for biomass and nitrogen estimation offers multiple opportunities for improving rice yields. UAV images provide detailed, high-resolution visual information about vegetation properties, enabling the identification of phenotypic characteristics for selecting the best varieties, improving yield predictions, and supporting ecosystem monitoring and conservation efforts. In this study, an analysis of biomass and nitrogen is conducted on 59 rice plots selected at random from a more extensive trial comprising 400 rice genotypes. A UAV acquires multispectral reflectance channels across a rice field of subplots containing different genotypes. Based on the ground-truth data, yields are characterized for the 59 plots and correlated with the Vegetation Indices (VIs) calculated from the photogrammetric mapping. The VIs are weighted by the segmentation of the plants from the soil and used as a feature matrix to estimate, via machine learning models, the biomass and nitrogen of the selected rice genotypes. The genotype IR 93346 presented the highest yield with a biomass gain of 10,252.78 kg/ha and an average daily biomass gain above 49.92 g/day. The VIs with the highest correlations with the ground-truth variables were NDVI and SAVI for wet biomass, GNDVI and NDVI for dry biomass, GNDVI and SAVI for height, and NDVI and ARVI for nitrogen. The machine learning model that performed best in estimating the variables of the 59 plots was the Gaussian Process Regression (GPR) model with a correlation factor of 0.98 for wet biomass, 0.99 for dry biomass, and 1 for nitrogen. The results presented demonstrate that it is possible to characterize the yields of rice plots containing different genotypes through ground-truth data and VIs.

Surgical indications for mediastinal cysts-a narrative review.

Background and Objective: Whether and when surgical intervention is indicated for mediastinal cysts is a matter of some debate. While most mediastinal cysts are found incidentally, the anatomic location, clinical presentation, and symptoms, as well as the potential for malignancy, are important considerations that inform decisions related to whether to intervene surgically. The objective of this review is to summarize the current literature regarding the criteria for surgical excision of mediastinal cysts and provide a framework for the clinician and surgeon to arrive at a decision regarding the appropriateness of surgical intervention of mediastinal cysts. Methods: A review of the published literature in the last 45 years (1977-2022) was conducted through PubMed, MeSh and Google Scholar. We included retrospective reviews, meta-analyses, and case studies published in the English language. A single author identified eligible studies, and those identified were reviewed by the team until consensus was met. Pediatric literature was excluded from this review. Key Content and Findings: The current literature predominantly contains case studies, small retrospective studies, and meta-analyses describing mediastinal cysts. In the anterior mediastinum, multiloculated thymic cysts should be resected to rule out thymic malignancy. Intralesional fat, smooth borders, and a more midline location are features suggestive of a benign process, while asymmetric cystic wall thickening has been associated with malignancy. Both esophageal and bronchogenic cysts should be excised, taking into account the risk of complications (up to a 45% risk) of infection, rupture, or compression, as well as the rare risk of associated malignancy. Simple thymic and small pericardial cysts can be observed and followed with serial radiographic tools and should be resected if they increase in size, compress surrounding structures, or lead the patient to develop symptoms. Conclusions: Since mediastinal cysts are rare and often asymptomatic, there are no formal guidelines outlining when surgical intervention should be undertaken. Based on our review of the literature, surgical intervention should be pursued if the patient's symptoms correlate with radiographic findings of a mediastinal cyst, there is compression of the surrounding structures, and concern of malignancy is present.

Postreperfusion Pulmonary Artery Pressure Indicates Primary Graft Dysfunction After Lung Transplant.

BACKGROUND: Primary graft dysfunction is a risk factor of early mortality after lung transplant. Models identifying patients at high risk for primary graft dysfunction are limited. We hypothesize high postreperfusion systolic pulmonary artery pressure is a clinical marker for primary graft dysfunction. METHODS: This is a retrospective review of 158 consecutive lung transplants performed at a single academic center from January 2020 through July 2022. Only bilateral lung transplants were included and patients with pretransplant extracorporeal life support were excluded. RESULTS: Primary graft dysfunction occurred in 42.3% (n = 30). Patients with primary graft dysfunction had higher postreperfusion systolic pulmonary artery pressure (41 ± 9.1 mm Hg) than those without (31.5 ± 8.8 mm Hg) (P < .001). Logistic regression showed postreperfusion systolic pulmonary artery pressure is a predictor for primary graft dysfunction (odds ratio 1.14, 95% CI 1.06-1.24, P < .001). Postreperfusion systolic pulmonary artery pressure of 37 mm Hg was optimal for predicting primary graft dysfunction by Youden index. The receiver operating characteristic curve of postreperfusion systolic pulmonary artery pressure at 37 mm Hg (sensitivity 0.77, specificity 0.78, area under the curve 0.81), was superior to the prereperfusion pressure curve at 36 mm Hg (sensitivity 0.77, specificity 0.39, area under the curve 0.57) (P < .01). CONCLUSIONS: Elevated postreperfusion systolic pulmonary artery pressure after lung transplant is predictive of primary graft dysfunction. Postreperfusion systolic pulmonary artery pressure is more indicative of primary graft dysfunction than prereperfusion systolic pulmonary artery pressure. Using postreperfusion systolic pulmonary artery pressure as a positive signal of primary graft dysfunction allows earlier intervention, which could improve outcomes.

IL-1ß-dependent extravasation of preexisting lung-restricted autoantibodies during lung transplantation activates complement and mediates primary graft dysfunction.

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1ß-mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.

Circulating Tumor-Macrophage Fusion Cells and Circulating Tumor Cells Complement Non-Small-Cell Lung Cancer Screening in Patients With Suspicious Lung-RADS 4 Nodules.

PURPOSE: Low-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4). METHODS: Prospectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months. RESULTS: In the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P < .005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients. CONCLUSION: Cellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.

Epigenetic Regulation of Cancer Immune Cells.

The epigenetic regulation of immune response involves reversible and heritable changes that do not alter the DNA sequence. Though there have been extensive studies accomplished relating to epigenetic changes in cancer cells, recent focus has been shifted on epigenetic-mediated changes in the immune cells including T cells, Macrophages, Natural Killer cells and anti-tumor immune responses. This review compiles the most relevant and recent literature related to the role of epigenetic mechanisms including DNA methylation and histone modifications in immune cells of wide range of cancers. We also include recent research with respect to role of the most relevant transcription factors that epigenetically control the anti-tumor immune response. Finally, a statement of future direction that promises to look forward for strategies to improve immunotherapy in cancer.

A novel method for isolation and culture of primary swine gastric epithelial cells.

BACKGROUND: Culturing primary epithelial cells has a major advantage over tumor-derived or immortalized cell lines as long as their functional phenotype and genetic makeup are mainly maintained. The swine model has shown to be helpful and reliable when used as a surrogate model for human diseases. Several porcine cell lines have been established based on a variety of tissues, which have shown to extensively contribute to the current understanding of several pathologies, especially cancer. However, protocols for the isolation and culture of swine gastric epithelial cells that preserve cell phenotype are rather limited. We aimed to develop a new method for establishing a primary epithelial cell culture from the fundic gland region of the pig stomach. RESULTS: Mechanical and enzymatic dissociation of gastric tissue was possible by combining collagenase type I and dispase II, protease inhibitors and antioxidants, which allowed the isolation of epithelial cells from the porcine fundic glands showing cell viability > 90% during the incubation period. Gastric epithelial cells cultured in RPMI 1640, DMEM-HG and DMEM/F12 media did not contribute enough to cell adhesion, cluster formation and cell proliferation. By contrast, William's E medium supplemented with growth factors supports confluency and proliferation of a pure epithelial cell monolayer after 10 days of incubation at 37 °C, 5% CO2. Mucin-producing cell phenotype of primary isolates was confirmed by PAS staining, MUC1 by immunohistochemistry, as well as the expression of MUC1 and MUC20 genes by RT-PCR and cDNA sequencing. Swine gastric epithelial cells also showed origin-specific markers such as cytokeratin cocktail (AE1/AE3) and cytokeratin 18 (CK-18) using immunohistochemical and immunofluorescence methods, respectively. CONCLUSIONS: A new method was successfully established for the isolation of primary gastric epithelial cells from the fundic gland zone through a swine model based on a combination of tissue-specific proteases, protease inhibitors and antioxidants after mechanical cell dissociation. The formulation of William's E medium with growth factors for epithelial cells contributes to cell adhesion and preserves functional primary cells phenotype, which is confirmed by mucin production and expression of typical epithelial markers over time.

Cost Utilization and the Use of Pulmonary Function Tests in Preoperative Liver Transplant Patients.

BACKGROUND: Pulmonary function tests (PFTs) are currently recommended for liver transplant candidates. We hypothesized that PFTs may not provide added clinical value to the evaluation of liver transplant patients. METHODS: We conducted a retrospective cohort study of adult cadaveric liver transplants from 2012 to 2018. Abnormal PFTs were defined as restrictive disease of diffusing capacity of the lungs for carbon monoxide (DLCO) <80% or obstructive disease of ratio of forced expiratory volume in the first 1 second to the first vital capacity of the lungs (FEV1/FVC) <70%. RESULTS: We analyzed data on 415 liver transplant patients (358 abnormal PFT results and 57 normal results). The liver transplant patients with abnormal PFTs had no difference in number of intensive care unit (ICU) days (P = .68), length of stay (P = .24), or intubation days (P = .33). There were no differences in pulmonary complications including pleural effusion (P = .30), hemo/pneumothorax (P = .74), pneumonia (P = .66), acute respiratory distress syndrome (P = .57), or pulmonary edema (P = .73). The significant finding between groups was a higher rate of reintubation in liver transplant patients with normal PFTs (P = .02). There was no difference in graft survival (P = .53) or patient survival (P = .42). DISCUSSION: Abnormal PFTs, found in 86% of liver transplant patients, did not correlate with complications, graft failure, or mortality. PFTs contribute to the high cost of liver transplants but do not help predict which patients are at risk of postoperative complications.

Pre-Liver Transplant Coronary Artery Disease Workup for Low-Risk Patients.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality following orthotopic liver transplant, yet there is no standardized protocol for pre-liver-transplant coronary artery disease assessment. The main objective of this study was to determine the agreement between 2 methods of cardiac risk assessment: dobutamine stress echocardiogram (DSE) and coronary calcium score (CCS) and to determine which test was best able to predict coronary calcification in low-risk patients. METHODS: A retrospective study was performed using the medical records of 436 patients who received cardiac clearance for a liver transplant. A total of 152 patients' medical records were included based on the inclusion of patients who had received both DSE and CCS. A kappa coefficient was calculated to determine the agreement between the DSE and CCS results. In addition, the positive predictive values (PPVs) of both the CCS and DSE along with cardiac catheterization indicating abdominal occlusion were analyzed to compare the accuracy of the 2 tests. RESULTS: It was determined that there was a 12% agreement between DSE results and CCS. It was found that the DSE had a PPV of 56% and the CCS had a PPV of 80%. CONCLUSION: From this data, it was concluded that there was no agreement between the results of the CCS and the DSE. While neither the CCS nor the DSE presents an optimal method of risk assessment, the CCS had a much higher PPV and was therefore determined to be the more accurate test.

Robotic-Assisted Total Pericardiectomy for Acute Relapsing Pericarditis: A Case Report.

Acute, relapsing pericarditis is an uncommon potential complication of any cardiothoracic intervention. If medical management fails to mitigate recurrent symptoms, robotic total pericardiectomy can be performed as a definitive therapeutic option. A 33-year-old woman had severely symptomatic, persistent pericarditis, which began 3 weeks after pacemaker placement for tachy-brady syndrome. After failure of pharmacologic treatment, a robot-assisted total pericardiectomy was performed with a drastic improvement in symptoms. Considering that this case of pericarditis was inflammatory (nonconstrictive), a radical excisional approach to all the pericardium was undertaken in order to prevent relapse of symptoms. A bilateral endoscopic off-pump robot-assisted approach was used to completely and fully excise both the anterior and posterior pericardium. In conclusion, we present a case of acute relapsing pericarditis in a very symptomatic patient who failed medical therapy and underwent a robotic totally endoscopic radical pericardiectomy with excellent results. We believe that this technique allows for total pericardiectomy using the least invasive approach and should be considered in the management of this rare but potentially debilitating condition.

Evaluación de torque de remoción en implantes dentales 3i, B&W y tree-oss. estudio experimentalen conejos / Evaluation of removal torque in 3i, B&W and tree-oss dental implants. an experimental study in rabbits

Objetivo: evaluar el torque de remoción de tres implantes con superficies diferentes, a los 60 días de inserción. Materiales y métodos: se midió la frecuencia de resonancia inicial y final y torque de remoción a los 60 días en 18 implantes: Biomet 3i (Palm Beach Gardens, FL, Estados Unidos); n=6; B&W (Buenos Aires, Argentina), n=6; Tree-Oss (Buenos Aires, Argentina), n=6; todos de 8,5 mm de longitud y 4 mm de diámetro. Los datos fueron sometidos al test no paramétrico de Mann-Whitney, al de Kruskal-Wallis y al de Wilcoxon. Resultados: la media de torque de remoción fue de 82,58 Ncm para implantes Biomet 3i; de 78,08 Ncm para B6W; y de 69 Ncm para Tree-Oss, sin diferencias estadísticamente significativas (p=0,220). La media de ISQ inicial y final fue de 57, 17 y 70,33 para Biomet 3i; de 56,33 y 62,07 para B6W y de 58,17 y 54,5 para Tree-Oss. Conclusión: los tres grupos de implantes presentan valores de torque de remoción similares, sin diferencias estadísticamente significativas pero con diferencias significativas en relación a ISQ final.

Aim: to evaluate the removal torque of three implants with different surfaces placed in rabbit femur, 60 days afterinsertion and to compare the implant stability quotient rightafter insertion and 60 days later.Materials and methods: Initial and final resonance frequency analysis and removal torque were measured at day60, in 18 parallel wall implants: Biomet 3i (Palm Beach Gardens, FL, USA), n=6; B&W (Buenos Aires, Argentina), n=6; Tree-Oss (Buenos Aires, Argentina), n=6; of 8.5 mm in lengthand 4 mm in diameter, placed in the femur of 6 rabbits. Datacollected were analyzed by nonparametric Mann-Whitney, Kruskal-Wallis and Wilcoxon tests. Results: The mean removal torques were 82,58 Ncm forBiomet 3i, 78,08 Ncm for B&W and 69 Ncm for Tree-Oss. Differences were not statistically significant (p=0.220). Inassessing initial and final ISQ, the averages obtained for Biomet3i were 57.17 and 70.33, respectively; for B&W 56.33 and62.67, and 58.17 and 54.5 for Tree-Oss. Conclusion: It is concluded that the three groups presented similar removal torque values with no statistically significant differences between them, but there were significant differences in relation to final ISQ.

High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner.

The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8(+) T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8(+) T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of "free" IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired.

IL-15 suppresses colitis-associated colon carcinogenesis by inducing antitumor immunity.

IL-15 regulates the development, survival, and proliferation of multiple innate and adaptive immune cells and plays a dual role, inducing both tumor cell growth and antitumor immunity. However, the role of IL-15 in inflammation-induced cancer remains unclear. To explore this, we have compared the colon carcinoma burden of Il15-/- and Il15rα -/- mice with wild type (WT) mice after induction of colitis-associated colon carcinogenesis utilizing the AOM/DSS model. Compared to WT mice, Il15-/- but not Il15rα -/- mice showed reduced survival, along with higher tumor incidence, colon weight, and tumor size. This suggests that low affinity IL-15 signaling via the shared IL-2Rß/γc decreases the risk for developing colitis-associated cancer. CD11c-Il15 mice, in which IL-15 expression is reconstituted in Il15-/- mice under the control of the CD11c-promoter, showed that selective reconstitution of IL-15 in antigen-presenting cells restored the CD8+ T and NK cell compartments, serum levels of IFNγ, G-CSF, IL-10, and CXCL1 and reduced tumor burden. After demonstrating IL-15 expression in human colorectal cancer (CRC) cells in situ, we investigated the role of this cytokine in the modulation of key colonic oncogenic pathways in the tumor. While these pathways were found to be unaltered in the absence of IL-15, tumor transcriptome analysis showed that the loss of IL-15 upregulates key inflammatory mediators associated with colon cancer progression, such as IL-1ß, IL-22, IL-23, Cxcl5, and Spp1. These findings provide evidence that IL-15 suppresses colitis-associated colon carcinogenesis through regulation of antitumor cytotoxicity, and modulation of the inflammatory tumor micromilieu.

A clone-free, single molecule map of the domestic cow (Bos taurus) genome.

BACKGROUND: The cattle (Bos taurus) genome was originally selected for sequencing due to its economic importance and unique biology as a model organism for understanding other ruminants, or mammals. Currently, there are two cattle genome sequence assemblies (UMD3.1 and Btau4.6) from groups using dissimilar assembly algorithms, which were complemented by genetic and physical map resources. However, past comparisons between these assemblies revealed substantial differences. Consequently, such discordances have engendered ambiguities when using reference sequence data, impacting genomic studies in cattle and motivating construction of a new optical map resource--BtOM1.0--to guide comparisons and improvements to the current sequence builds. Accordingly, our comprehensive comparisons of BtOM1.0 against the UMD3.1 and Btau4.6 sequence builds tabulate large-to-immediate scale discordances requiring mediation. RESULTS: The optical map, BtOM1.0, spanning the B. taurus genome (Hereford breed, L1 Dominette 01449) was assembled from an optical map dataset consisting of 2,973,315 (439 X; raw dataset size before assembly) single molecule optical maps (Rmaps; 1 Rmap = 1 restriction mapped DNA molecule) generated by the Optical Mapping System. The BamHI map spans 2,575.30 Mb and comprises 78 optical contigs assembled by a combination of iterative (using the reference sequence: UMD3.1) and de novo assembly techniques. BtOM1.0 is a high-resolution physical map featuring an average restriction fragment size of 8.91 Kb. Comparisons of BtOM1.0 vs. UMD3.1, or Btau4.6, revealed that Btau4.6 presented far more discordances (7,463) vs. UMD3.1 (4,754). Overall, we found that Btau4.6 presented almost double the number of discordances than UMD3.1 across most of the 6 categories of sequence vs. map discrepancies, which are: COMPLEX (misassembly), DELs (extraneous sequences), INSs (missing sequences), ITs (Inverted/Translocated sequences), ECs (extra restriction cuts) and MCs (missing restriction cuts). CONCLUSION: Alignments of UMD3.1 and Btau4.6 to BtOM1.0 reveal discordances commensurate with previous reports, and affirm the NCBI's current designation of UMD3.1 sequence assembly as the "reference assembly" and the Btau4.6 as the "alternate assembly." The cattle genome optical map, BtOM1.0, when used as a comprehensive and largely independent guide, will greatly assist improvements to existing sequence builds, and later serve as an accurate physical scaffold for studies concerning the comparative genomics of cattle breeds.

Antimony resistance and trypanothione in experimentally selected and clinical strains of Leishmania panamensis.

The participation of trypanothione in clinical and experimental antimony (Sb) resistance in Leishmania panamensis was examined by using specific inhibitors. Buthionine sulfoximine (BSO) significantly reversed the resistance to trivalent Sb (Sb(III)) of promastigotes of experimentally derived Sb-resistant lines, supporting the participation of a trypanothione-mediated mechanism of resistance. In contrast, promastigotes of strains isolated at the time of clinical treatment failure and resistant to pentavalent Sb (Sb(V)) as intracellular amastigotes were not cross resistant to Sb(III), and BSO had little or no effect on susceptibility. Difluoromethylornithine did not alter the Sb(III) susceptibilities of experimentally selected lines or clinical strains. The mechanisms of acquired resistance emerging in clinical settings may differ from those selected by in vitro exposure to Sb.