Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

Assessing the national trends in colon cancer among Native Americans: A 12 year SEER database study

Introduction: Native Americans (NA) form a unique cohort of colon cancer (CC) patients among whom the variability in demographics and cancer characteristics remains unclear. Methods: We abstracted the national estimates for NA with CC using the Surveillance, Epidemiology, and End Result (SEER) database. Trend analysis of incidence, variation in location and patient demographic analysis were performed. Results: A total number of 26,674 NA with CC were reported during the 12-year study period. While the overall incidence of CC decreased by 12% during the study period, incidence increased by 38% in NA. Incidence of CC was more prevalent and higher increase (42%) seen in NA females than males (p = 0.02; 34%). Stage III tumors represented 29% of all CC, sigmoid colon the most common site location (38%) with 72% of all tumors being moderately differentiated. 55% tumors were localized in left, 36% in right and 9% in transverse colon. 92% of the NA were insured. Conclusion: Incidence of CC continues to rise in NA with majority of CC presented at higher stage and moderate differentiation. Published by Elsevier Inc.NCI Cancer Center Support Grant [P30 CA023074]12 month embargo; available online 22 November 2016.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Native or Non-Native Protein-Protein Docking Models? Molecular Dynamics to the Rescue

Molecular docking excels at creating a plethora of potential models of protein-protein complexes. To correctly distinguish the favorable, native-like models from the remaining ones remains, however, a challenge. We assessed here if a protocol based on molecular dynamics (MD) simulations would allow distinguishing native from non-native models to complement scoring functions used in docking. To this end, the first models for 25 protein-protein complexes were generated using HADDOCK. Next, MD simulations complemented with machine learning were used to discriminate between native and non-native complexes based on a combination of metrics reporting on the stability of the initial models. Native models showed higher stability in almost all measured properties, including the key ones used for scoring in the Critical Assessment of PRedicted Interaction (CAPRI) competition, namely the positional root mean square deviations and fraction of native contacts from the initial docked model. A random forest classifier was trained, reaching a 0.85 accuracy in correctly distinguishing native from non-native complexes. Reasonably modest simulation lengths of the order of 50-100 ns are sufficient to reach this accuracy, which makes this approach applicable in practice

Multiple Hypersensitivities Including Recurrent Airway Obstruction, Insect Bite Hypersensitivity, and Urticaria in 2 Warmblood Horse Populations.

BACKGROUND Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. HYPOTHESES Horses suffering from recurrent airway obstruction (RAO), insect bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. ANIMALS The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. METHODS Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. RESULTS In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. CONCLUSIONS AND CLINICAL IMPORTANCE This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses

Temporal evolution study of the plasma induced by CO2 pulsed laser on targets of titanium oxides

This paper reports studies on time-resolved laser induced breakdown spectroscopy (LIBS) of plasmas induced by IR nanosecond laser pulses on the titanium oxides TiO and TiO2 (anatase). LIBS excitation was performed using a CO2 laser. The laser-induced plasma was found strongly ionized yielding Ti+, O+, Ti2 +, O 2 +, Ti3 +, and Ti4 + species and rich in neutral titanium and oxygen atoms. The temporal behavior of specific emission lines of Ti, Ti+, Ti2 + and Ti3 + was characterized. The results show a faster decay of Ti3 + and Ti 2 + ionic species than that of Ti+ and neutral Ti atoms. Spectroscopic diagnostics were used to determine the time-resolved electron density and excitation temperatures. Laser irradiation of TiO 2-anatase induces on the surface sample the polymorphic transformation to TiO2-rutile. The dependence on fluence and number of irradiation pulses of this transformation was studied by micro-Raman spectroscopy. © 2013 Elsevier B.V.We gratefully acknowledge the support received in part by the DGICYT (MICINN, Spain) Projects: CTQ2008-05393/BQU and CTQ2010- 15680/BQU for this research. M.S. thanks CAM (Geomateriales S2009/ MAT 1629) for a contract.Peer Reviewe