Giant thermoelectric effect in Al2O3 magnetic tunnel junctions

Thermoelectric effects in magnetic nanostructures and the so-called spin caloritronics are attracting much interest. Indeed it provides a new way to control and manipulate spin currents which are key elements of spin-based electronics. Here we report on giant magnetothermoelectric effect in Al2O3 magnetic tunnel junctions. The thermovoltage in this geometry can reach 1 mV. Moreover a magneto-thermovoltage effect could be measured with ratio similar to the tunnel magnetoresistance ratio. The Seebeck coefficient can then be tuned by changing the relative magnetization orientation of the two magnetic layers in the tunnel junction. Therefore our experiments extend the range of spintronic devices application to thermoelectricity and provide a crucial piece of information for understanding the physics of thermal spin transport.Comment: 9 pages, 7 figures, added reference

Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study

BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. METHODS: Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. RESULTS: Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis

Heterogeneity of mammary lesions represent molecular differences

BACKGROUND: Human breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies. METHODS: We utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution. RESULTS: We demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes that occur in the transition to invasive carcinoma are subtle, with few consistent changes and no association with phenotype. CONCLUSION: We propose that the early lesions carry the important genetic changes that reflect the major phenotypic information, while additional genetic changes that accumulate in the invasive carcinoma are less associated with the overall phenotype

Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter

Different studies have reported the prevalence of Salmonella in turtles and its role in reptile-associated salmonellosis in humans, but there is a lack of scientific literature related with the epidemiology of Campylobacter in turtles. The aim of this study was to evaluate the prevalence of Campylobacter and Salmonella in free-living native (Emys orbicularis, n=83) and exotic (Trachemys scripta elegans, n=117) turtles from 11 natural ponds in Eastern Spain. In addition, different types of samples (cloacal swabs, intestinal content and water from Turtle containers) were compared. Regardless of the turtle species, natural ponds where individuals were captured and the type of sample taken, Campylobacter was not detected. Salmonella was isolated in similar proportions in native (8.0±3.1%) and exotic (15.0±3.3%) turtles (p=0.189). The prevalence of Salmonella positive turtles was associated with the natural ponds where animals were captured. Captured turtles from 8 of the 11 natural ponds were positive, ranged between 3.0±3.1% and 60.0±11.0%. Serotyping revealed 8 different serovars among four Salmonella enterica subspecies: S. enterica subsp. enterica (n = 21), S. enterica subsp. salamae (n = 2), S. enterica subsp. diarizonae (n = 3), and S. enterica subsp. houtenae (n = 1). Two serovars were predominant: S. Thompson (n=16) and S. typhimurium (n=3). In addition, there was an effect of sample type on Salmonella detection. The highest isolation of Salmonella was obtained from intestinal content samples (12.0±3.0%), while lower percentages were found for water from the containers and cloacal swabs (8.0±2.5% and 3.0±1.5%, respectively). Our results imply that free-living turtles are a risk factor for Salmonella transmission, but do not seem to be a reservoir for Campylobacter. We therefore rule out turtles as a risk factor for human campylobacteriosis. Nevertheless, further studies should be undertaken in other countries to confirm these results.This work was supported by the Conselleria de Infraestructura, Territorio y Medio Ambiente for their assistance and financial support (Life09-Trachemys, Resolution 28/02/12 CITMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marín, C.; Ingresa-Capaccioni, S.; González Bodí, S.; Marco Jiménez, F.; Vega Garcia, S. (2013). Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter. PLoS ONE. 8(8):1-6. https://doi.org/10.1371/journal.pone.0072350S1688(2012). The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food‐borne Outbreaks in 2010. EFSA Journal, 10(3). doi:10.2903/j.efsa.2012.2597Kapperud, G. (2003). Factors Associated with Increased and Decreased Risk of Campylobacter Infection: A Prospective Case-Control Study in Norway. 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(2002). Salmonella Infection Associated With a Pet Lizard in Siblings With Sickle Cell Anemia: An Avoidable Risk. Journal of Pediatric Hematology/Oncology, 24(1), 75-76. doi:10.1097/00043426-200201000-00020Tu, Z.-C., Zeitlin, G., Gagner, J.-P., Keo, T., Hanna, B. A., & Blaser, M. J. (2004). Campylobacter fetus of Reptile Origin as a Human Pathogen. Journal of Clinical Microbiology, 42(9), 4405-4407. doi:10.1128/jcm.42.9.4405-4407.2004Hidalgo-Vila, J., Díaz-Paniagua, C., Pérez-Santigosa, N., de Frutos-Escobar, C., & Herrero-Herrero, A. (2008). Salmonella in free-living exotic and native turtles and in pet exotic turtles from SW Spain. Research in Veterinary Science, 85(3), 449-452. doi:10.1016/j.rvsc.2008.01.011Harris, J. R., Neil, K. P., Behravesh, C. B., Sotir, M. J., & Angulo, F. J. (2010). Recent Multistate Outbreaks of HumanSalmonellaInfections Acquired from Turtles: A Continuing Public Health Challenge. Clinical Infectious Diseases, 50(4), 554-559. doi:10.1086/649932Geue, L., & Löschner, U. (2002). Salmonella enterica in reptiles of German and Austrian origin. Veterinary Microbiology, 84(1-2), 79-91. doi:10.1016/s0378-1135(01)00437-0Sánchez-Jiménez, M. M., Rincón-Ruiz, P. A., Duque, S., Giraldo, M. A., Ramírez-Monroy, D. M., Jaramillo, G., & Cardona-Castro, N. (2011). Salmonella enterica in semi-aquatic turtles in Colombia. The Journal of Infection in Developing Countries, 5(05), 361-364. doi:10.3855/jidc.1126HEALTH SURVEY OF WILD AND CAPTIVE BOG TURTLES (CLEMMYS MUHLENBERGII) IN NORTH CAROLINA AND VIRGINIA. (2002). Journal of Zoo and Wildlife Medicine, 33(4), 311-316. doi:10.1638/1042-7260(2002)033[0311:hsowac]2.0.co;2Richards, J. M., Brown, J. D., Kelly, T. R., Fountain, A. L., & Sleeman, J. M. (2004). ABSENCE OF DETECTABLE SALMONELLA CLOACAL SHEDDING IN FREE-LIVING REPTILES ON ADMISSION TO THE WILDLIFE CENTER OF VIRGINIA. Journal of Zoo and Wildlife Medicine, 35(4), 562-563. doi:10.1638/03-070Hidalgo-Vila, J., Díaz-Paniagua, C., de Frutos-Escobar, C., Jiménez-Martínez, C., & Pérez-Santigosa, N. (2007). Salmonella in free living terrestrial and aquatic turtles. Veterinary Microbiology, 119(2-4), 311-315. doi:10.1016/j.vetmic.2006.08.012Acheson, D., & Allos, B. M. (2001). Campylobacter jejuni Infections: Update on Emerging Issues and Trends. Clinical Infectious Diseases, 32(8), 1201-1206. doi:10.1086/319760Briones, V., Tellez, S., Goyache, J., Ballesteros, C., del Pilar Lanzarot, M., Dominguez, L., & Fernandez-Garayzabal, J. F. (2004). Salmonella diversity associated with wild reptiles and amphibians in Spain. Environmental Microbiology, 6(8), 868-871. doi:10.1111/j.1462-2920.2004.00631.xMan, S. M. (2011). The clinical importance of emerging Campylobacter species. Nature Reviews Gastroenterology & Hepatology, 8(12), 669-685. doi:10.1038/nrgastro.2011.191Ugarte-Ruiz, M., Gómez-Barrero, S., Porrero, M. 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FGFR1 and NTRK3 actionable alterations in “Wild-Type” gastrointestinal stromal tumors

BACKGROUND: About 10–15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies. METHODS: We performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations. RESULTS: We identified 24 GIST lacking alterations in the canonical KIT/PDGFRA/RAS pathways, including 12 without SDHx alterations. These 24 patients were mostly adults (96%). The tumors had a 46% rate of nodal metastases. These 24 GIST were more commonly mutated at 7 genes: ARID1B, ATR, FGFR1, LTK, SUFU, PARK2 and ZNF217. Two tumors harbored FGFR1 gene fusions (FGFR1–HOOK3, FGFR1–TACC1) and one harbored an ETV6–NTRK3 fusion that responded to TRK inhibition. In an independent sample set, we identified 5 GIST cases lacking alterations in the KIT/PDGFRA/SDHx/RAS pathways, including two additional cases with FGFR1–TACC1 and ETV6–NTRK3 fusions. CONCLUSIONS: Using patient demographics, tumor characteristics, and CGP, we show that GIST lacking alterations in canonical genes occur in younger patients, frequently metastasize to lymph nodes, and most contain deleterious genomic alterations, including gene fusions involving FGFR1 and NTRK3. If confirmed in larger series, routine testing for these translocations may be indicated for this subset of GIST. Moreover, these findings can be used to guide personalized treatments for patients with GIST. Trial registration NCT 02576431. Registered October 12, 2015 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-1075-6) contains supplementary material, which is available to authorized users