First observations of the X-ray transient EXO 2030+375 with IBIS/ISGRI

We present a first INTEGRAL observation of the 42s transient X-ray pulsar EXO 2030+375 with IBIS/ISGRI. The source was detected during Cyg X-1 observations in December 2002. We analyzed observations during the outburst period from 9 to 21 December 2002 with a total exposure time of ~770 kiloseconds. EXO 2030+375 was almost always detected during single ~30 minute exposures in the 18-45 energy bands. The source light curve shows the characteristic outburst shape observed in this source.Comment: 4 pages, 3 figures (1 in CMYK color), accepted by Astronomy and Astrophysics, INTEGRAL special issue, 200

NuSTAR rules out a cyclotron line in the accreting magnetar candidate 4U2206+54

Based on our new NuSTAR X-ray telescope data, we rule out any cyclotron line up to 60 keV in the spectra of the high-mass X-ray binary 4U2206+54. In particular, we do not find any evidence of the previously claimed line around 30 keV, independently of the source flux, along the spin pulse. The spin period has increased significantly, since the last observation, up to 5750 ± 10 s, confirming the rapid spin-down rate ν˙=−1.8×10−14 Hz s−1. This behaviour might be explained by the presence of a strongly magnetized neutron star (Bs > several times 1013 G) accreting from the slow wind of its main-sequence O9.5 companion.This research has been supported by the grant ESP2017-85691-P. KP acknowledges support from the Russian Foundation for Basic Research grant 18-502-12025

Genetic inhibition of flowering differs between juvenile and adult Citrus trees

[EN] Background and Aims In woody species, the juvenile period maintains the axillary meristems in a vegetative stage, unable to flower, for several years. However, in adult trees, some 1-year-old meristems flower whereas others remain vegetative to ensure a polycarpic growth habit. Both types of trees, therefore, have non-flowering meristems, and we hypothesize that the molecular mechanism regulating flower inhibition in juvenile trees is different from that in adult trees. Methods In adult Citrus trees, the main endogenous factor inhibiting flower induction is the growing fruit. Thus, we studied the expression of the main flowering time, identity and patterning genes of trees with heavy fruit load (not-flowering adult trees) compared to that of 6-month-old trees (not-flowering juvenile trees). Adult trees without fruits (flowering trees) were used as a control. Second, we studied the expression of the same genes in the meristems of 6-month, and 1-, 3-, 5-and 7-year-old juvenile trees compared to 10-year-old flowering trees. Key Results The axillary meristems of juvenile trees are unable to transcribe flowering time and patterning genes during the period of induction, although they are able to transcribe the FLOWERING LOCUS T citrus orthologue (CiFT2) in leaves. By contrast, meristems of not-flowering adult trees are able to transcribe the flowering network genes but fail to achieve the transcription threshold required to flower, due to CiFT2 repression by the fruit. Juvenile meristems progressively achieve gene expression, with age-dependent differences from 6 months to 7 years, FD-like and CsLFY being the last genes to be expressed. Conclusions During the juvenile period the mechanism inhibiting flowering is determined in the immature bud, so that it progressively acquires flowering ability at the gene expression level of the flowering time programme, whereas in the adult tree it is determined in the leaf, where repression of CiFT2 gene expression occurs.We thank Cristina Ferrandiz (IBMCP-UPV, Spain) and Fernando Andres (UMR AGAP, France) for useful comments on the manuscript. We thank D. Westall for her help in editing the manuscript. This work was supported by a grant from the Ministerio de Economia y Competitividad, Spain (RTA2013-0024-C02-02)Muñoz Fambuena, N.; Nicolas-Almansa, M.; Martinez Fuentes, A.; Reig Valor, C.; Iglesias, DJ.; Primo-Millo, E.; Mesejo Conejos, C.... (2019). Genetic inhibition of flowering differs between juvenile and adult Citrus trees. Annals of Botany. 123(3):483-490. https://doi.org/10.1093/aob/mcy179S4834901233Abe, M. (2005). FD, a bZIP Protein Mediating Signals from the Floral Pathway Integrator FT at the Shoot Apex. Science, 309(5737), 1052-1056. doi:10.1126/science.1115983Albani, M. C., & Coupland, G. (2010). Comparative Analysis of Flowering in Annual and Perennial Plants. Plant Development, 323-348. doi:10.1016/s0070-2153(10)91011-9Andrés, F., & Coupland, G. (2012). The genetic basis of flowering responses to seasonal cues. Nature Reviews Genetics, 13(9), 627-639. doi:10.1038/nrg3291Balanzà, V., Martínez-Fernández, I., Sato, S., Yanofsky, M. F., Kaufmann, K., Angenent, G. C., … Ferrándiz, C. (2018). Genetic control of meristem arrest and life span in Arabidopsis by a FRUITFULL-APETALA2 pathway. Nature Communications, 9(1). doi:10.1038/s41467-018-03067-5Bäurle, I., & Dean, C. (2006). The Timing of Developmental Transitions in Plants. Cell, 125(4), 655-664. doi:10.1016/j.cell.2006.05.005Betancourt, M., Sistachs, V., Martínez-Fuentes, A., Mesejo, C., Reig, C., & Agustí, M. (2014). Influence of harvest date on fruit yield and return bloom in ‘Marsh’ grapefruit trees (Citrus paradisiMacf.) grown under a tropical climate. The Journal of Horticultural Science and Biotechnology, 89(4), 435-440. doi:10.1080/14620316.2014.11513103Blázquez, M. A., Ferrándiz, C., Madueño, F., & Parcy, F. (2006). How Floral Meristems are Built. Plant Molecular Biology, 60(6), 855-870. doi:10.1007/s11103-006-0013-zBlümel, M., Dally, N., & Jung, C. (2015). Flowering time regulation in crops — what did we learn from Arabidopsis? Current Opinion in Biotechnology, 32, 121-129. doi:10.1016/j.copbio.2014.11.023Castillo, M.-C., Forment, J., Gadea, J., Carrasco, J. L., Juarez, J., Navarro, L., & Ancillo, G. (2013). Identification of transcription factors potentially involved in the juvenile to adult phase transition in Citrus. Annals of Botany, 112(7), 1371-1381. doi:10.1093/aob/mct211Chica, E. J., & Albrigo, L. G. (2013). Expression of Flower Promoting Genes in Sweet Orange during Floral Inductive Water Deficits. Journal of the American Society for Horticultural Science, 138(2), 88-94. doi:10.21273/jashs.138.2.88Endo, T., Shimada, T., Fujii, H., Kobayashi, Y., Araki, T., & Omura, M. (2005). Ectopic Expression of an FT Homolog from Citrus Confers an Early Flowering Phenotype on Trifoliate Orange (Poncirus trifoliata L. Raf.). Transgenic Research, 14(5), 703-712. doi:10.1007/s11248-005-6632-3Haberman, A., Ackerman, M., Crane, O., Kelner, J.-J., Costes, E., & Samach, A. (2016). Different flowering response to various fruit loads in apple cultivars correlates with degree of transcript reaccumulation of a TFL1-encoding gene. The Plant Journal, 87(2), 161-173. doi:10.1111/tpj.13190Hanano, S., & Goto, K. (2011). Arabidopsis TERMINAL FLOWER1 Is Involved in the Regulation of Flowering Time and Inflorescence Development through Transcriptional Repression. The Plant Cell, 23(9), 3172-3184. doi:10.1105/tpc.111.088641Mafra, V., Kubo, K. S., Alves-Ferreira, M., Ribeiro-Alves, M., Stuart, R. M., Boava, L. P., … Machado, M. A. (2012). Reference Genes for Accurate Transcript Normalization in Citrus Genotypes under Different Experimental Conditions. PLoS ONE, 7(2), e31263. doi:10.1371/journal.pone.0031263Martínez-Fuentes, A., Mesejo, C., Reig, C., & Agustí, M. (2010). Timing of the inhibitory effect of fruit on return bloom of ‘Valencia’ sweet orange (Citrus sinensis (L.) Osbeck). Journal of the Science of Food and Agriculture, 90(11), 1936-1943. doi:10.1002/jsfa.4038Michaels, S. D., & Amasino, R. M. (1999). FLOWERING LOCUS C Encodes a Novel MADS Domain Protein That Acts as a Repressor of Flowering. The Plant Cell, 11(5), 949-956. doi:10.1105/tpc.11.5.949Muñoz-Fambuena, N., Mesejo, C., Carmen González-Mas, M., Primo-Millo, E., Agustí, M., & Iglesias, D. J. (2011). Fruit regulates seasonal expression of flowering genes in alternate-bearing ‘Moncada’ mandarin. Annals of Botany, 108(3), 511-519. doi:10.1093/aob/mcr164Muñoz-Fambuena, N., Mesejo, C., González-Mas, M. C., Primo-Millo, E., Agustí, M., & Iglesias, D. J. (2012). Fruit load modulates flowering-related gene expression in buds of alternate-bearing ‘Moncada’ mandarin. Annals of Botany, 110(6), 1109-1118. doi:10.1093/aob/mcs190Nishikawa, F., Endo, T., Shimada, T., Fujii, H., Shimizu, T., Omura, M., & Ikoma, Y. (2007). Increased CiFT abundance in the stem correlates with floral induction by low temperature in Satsuma mandarin (Citrus unshiu Marc.). Journal of Experimental Botany, 58(14), 3915-3927. doi:10.1093/jxb/erm246Peña, L., Martín-Trillo, M., Juárez, J., Pina, J. A., Navarro, L., & Martínez-Zapater, J. M. (2001). Constitutive expression of Arabidopsis LEAFY or APETALA1 genes in citrus reduces their generation time. Nature Biotechnology, 19(3), 263-267. doi:10.1038/85719Pillitteri, L. J., Lovatt, C. J., & Walling, L. L. (2004). Isolation and Characterization of a TERMINAL FLOWER Homolog and Its Correlation with Juvenility in Citrus. Plant Physiology, 135(3), 1540-1551. doi:10.1104/pp.103.036178Seo, E., Lee, H., Jeon, J., Park, H., Kim, J., Noh, Y.-S., & Lee, I. (2009). Crosstalk between Cold Response and Flowering in Arabidopsis Is Mediated through the Flowering-Time Gene SOC1 and Its Upstream Negative Regulator FLC. The Plant Cell, 21(10), 3185-3197. doi:10.1105/tpc.108.063883Sgamma, T., Jackson, A., Muleo, R., Thomas, B., & Massiah, A. (2014). TEMPRANILLO is a regulator of juvenility in plants. Scientific Reports, 4(1). doi:10.1038/srep03704Shalom, L., Samuels, S., Zur, N., Shlizerman, L., Zemach, H., Weissberg, M., … Sadka, A. (2012). Alternate Bearing in Citrus: Changes in the Expression of Flowering Control Genes and in Global Gene Expression in ON- versus OFF-Crop Trees. PLoS ONE, 7(10), e46930. doi:10.1371/journal.pone.0046930Shalom, L., Samuels, S., Zur, N., Shlizerman, L., Doron-Faigenboim, A., Blumwald, E., & Sadka, A. (2014). Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds. Journal of Experimental Botany, 65(12), 3029-3044. doi:10.1093/jxb/eru148Sohn, E. J., Rojas-Pierce, M., Pan, S., Carter, C., Serrano-Mislata, A., Madueno, F., … Raikhel, N. V. (2007). The shoot meristem identity gene TFL1 is involved in flower development and trafficking to the protein storage vacuole. Proceedings of the National Academy of Sciences, 104(47), 18801-18806. doi:10.1073/pnas.0708236104Spiegel-Roy, P., & Goldschmidt, E. E. (1996). The Biology of Citrus. doi:10.1017/cbo9780511600548Sussmilch, F. C., Berbel, A., Hecht, V., Vander Schoor, J. K., Ferrándiz, C., Madueño, F., & Weller, J. L. (2015). Pea VEGETATIVE2 Is an FD Homolog That Is Essential for Flowering and Compound Inflorescence Development. The Plant Cell, 27(4), 1046-1060. doi:10.1105/tpc.115.136150Tan, F.-C., & Swain, S. M. (2007). Functional characterization of AP3, SOC1 and WUS homologues from citrus (Citrus sinensis). Physiologia Plantarum, 131(3), 481-495. doi:10.1111/j.1399-3054.2007.00971.xLeal Valentim, F., Mourik, S. van, Posé, D., Kim, M. C., Schmid, M., van Ham, R. C. H. J., … van Dijk, A. D. J. (2015). A Quantitative and Dynamic Model of the Arabidopsis Flowering Time Gene Regulatory Network. PLOS ONE, 10(2), e0116973. doi:10.1371/journal.pone.0116973Wang, J.-W., Czech, B., & Weigel, D. (2009). miR156-Regulated SPL Transcription Factors Define an Endogenous Flowering Pathway in Arabidopsis thaliana. Cell, 138(4), 738-749. doi:10.1016/j.cell.2009.06.014Weigel, D. (1995). The Genetics of Flower Development: From Floral Induction to Ovule Morphogenesis. Annual Review of Genetics, 29(1), 19-39. doi:10.1146/annurev.ge.29.120195.00031

Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test

[EN] Background. Simultaneous pancreas-kidney (SPK) transplantation is a proven option of treatment for patients with type 1 diabetes mellitus (T1DM) and related end-stage renal disease. There is discrepancy between the results of different studies about the impact of prolonged normalization of glucose metabolism achieved by SPK on the course of diabetic complications including severe forms of diabetic neuropathy. The objective of the study was to evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) in patients undergoing SPK transplantation and its evolution 10 years after transplantation. Methods. Prospective study of 81 patients transplanted in a single center from year 2002 to 2015. Autonomic function was assessed using cardiovascular autonomic reflex tests (CARTs). CARTs were made before SPK transplantation and during the follow-up. Evolution of tests after SPK transplantation was evaluated by contrasting hypotheses (paired tests). Multiple testing was adjusted with the Benjamini-Hochberg procedure with a false discovery rate of 10%. Results. 48 males and 33 females, mean age 37.4 +/- 5.7 years, mean BMI 24.0 +/- 3.4 kg/m2, and mean duration of diabetes 25.5 +/- 6.5 years, received SPK transplantation. Ten years after SPK transplantation, 56 patients re tained the pancreatic graft (42 of them with normofunctioning pancreas and 14 with low doses of insulin therapy). These 42 patients were selected for the autonomic study. Before transplant procedure, all CART results were abnormal. After SPK transplantation, paired test analysis showed an improvement of systolic blood pressure (SBP) response to orthostasis at the 5(th) year after SPK (p=0.03), as well as improvement of the Valsalva ratio at the 3(rd) (p<0.001) and 5(th) (p=0.001) year after SPK. After correcting for the false discovery rate, all the variables of autonomic study reached significance at different time points. Conclusions. Prevalence of CAN in patients who are candidates for SPK transplantation is high and is generally advanced. SPK transplantation improves CAN with improved Valsalva ratio as the most precocious test.Argente-Pla, M.; Pérez-Lázaro, A.; Martinez-Millana, A.; Del Olmo-García, MI.; Espí-Reig, J.; Beneyto-Castello, I.; López-Andújar, R.... (2020). Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test. Journal of Diabetes Research. 2020:1-10. https://doi.org/10.1155/2020/7574628S1102020Freeman, R. (2014). Diabetic autonomic neuropathy. Handbook of Clinical Neurology, 63-79. doi:10.1016/b978-0-444-53480-4.00006-0Maser, R. E., Mitchell, B. D., Vinik, A. I., & Freeman, R. (2003). The Association Between Cardiovascular Autonomic Neuropathy and Mortality in Individuals With Diabetes: A meta-analysis. Diabetes Care, 26(6), 1895-1901. doi:10.2337/diacare.26.6.1895Dimitropoulos, G. (2014). Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes, 5(1), 17. doi:10.4239/wjd.v5.i1.17Vinik, A. I., & Ziegler, D. (2007). Diabetic Cardiovascular Autonomic Neuropathy. Circulation, 115(3), 387-397. doi:10.1161/circulationaha.106.634949Kennedy, W. R., Navarro, X., & Sutherland, D. E. R. (1995). Neuropathy profile of diabetic patients in a pancreas transplantation program. Neurology, 45(4), 773-780. doi:10.1212/wnl.45.4.773Pop-Busui, R., Boulton, A. J. M., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., … Ziegler, D. (2016). Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care, 40(1), 136-154. doi:10.2337/dc16-2042Balcıoğlu, A. S. (2015). Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment. World Journal of Diabetes, 6(1), 80. doi:10.4239/wjd.v6.i1.80Pop-Busui, R., Low, P. A., Waberski, B. H., Martin, C. L., Albers, J. W., Feldman, E. L., … Herman, W. H. (2009). Effects of Prior Intensive Insulin Therapy on Cardiac Autonomic Nervous System Function in Type 1 Diabetes Mellitus. Circulation, 119(22), 2886-2893. doi:10.1161/circulationaha.108.837369Maser, R. E., Lenhard, J. M., & DeCherney, S. G. (2000). Cardiovascular Autonomic Neuropathy. The Endocrinologist, 10(1), 27-33. doi:10.1097/00019616-200010010-00006Vinik, A. I., Erbas, T., & Casellini, C. M. (2013). Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. Journal of Diabetes Investigation, 4(1), 4-18. doi:10.1111/jdi.12042Ewing, D. J., Campbell, I. W., Murray, A., Neilson, J. M., & Clarke, B. F. (1978). Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes. BMJ, 1(6106), 145-147. doi:10.1136/bmj.1.6106.145In This Issue of Diabetes Care. (2019). Diabetes Care, 43(1), 1-2. doi:10.2337/dc20-ti01Gremizzi, C., Vergani, A., Paloschi, V., & Secchi, A. (2010). Impact of pancreas transplantation on type 1 diabetes-related complications. Current Opinion in Organ Transplantation, 15(1), 119-123. doi:10.1097/mot.0b013e32833552bcKennedy, W. R., Navarro, X., Goetz, F. C., Sutherland, D. E. R., & Najarian, J. S. (1990). Effects of Pancreatic Transplantation on Diabetic Neuropathy. New England Journal of Medicine, 322(15), 1031-1037. doi:10.1056/nejm199004123221503Bouček, P., Bartoš, V., Vaněk, I., Hýža, Z., & Skibová, J. (1991). Diabetic autonomic neuropathy after pancreas and kidney transplantation. Diabetologia, 34(S1), S121-S124. doi:10.1007/bf00587636Navarro, X., Sutherland, D. E. R., & Kennedy, W. R. (1997). Long-term effects of pancreatic transplantation on diabetic neuropathy. Annals of Neurology, 42(5), 727-736. doi:10.1002/ana.410420509Solders, G., Tyden, G., Persson, A., & Groth, C.-G. (1992). Improvement of Nerve Conduction in Diabetic Neuropathy: A Follow-up Study 4 Yr After Combined Pancreatic and Renal Transplantation. Diabetes, 41(8), 946-951. doi:10.2337/diab.41.8.946Argente-Pla, M., Martínez-Millana, A., Del Olmo-García, M. I., Espí-Reig, J., Pérez-Rojas, J., Traver-Salcedo, V., & Merino-Torres, J. F. (2019). Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review. Annals of Transplantation, 24, 608-616. doi:10.12659/aot.920106Sundkvist, G., & Lilja, B. (1985). Autonomic Neuropathy in Diabetes Mellitus: A Follow-up Study. Diabetes Care, 8(2), 129-133. doi:10.2337/diacare.8.2.129Boulton, A. J. M., Vinik, A. I., Arezzo, J. C., Bril, V., Feldman, E. L., Freeman, R., … Ziegler, D. (2005). Diabetic Neuropathies: A statement by the American Diabetes Association. Diabetes Care, 28(4), 956-962. doi:10.2337/diacare.28.4.956Ewing, D. J., Martyn, C. N., Young, R. J., & Clarke, B. F. (1985). The Value of Cardiovascular Autonomic Function Tests: 10 Years Experience in Diabetes. Diabetes Care, 8(5), 491-498. doi:10.2337/diacare.8.5.491Spallone, V., Bellavere, F., Scionti, L., Maule, S., Quadri, R., Bax, G., … Morganti, R. (2011). Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy☆. Nutrition, Metabolism and Cardiovascular Diseases, 21(1), 69-78. doi:10.1016/j.numecd.2010.07.005Agashe, S., & Petak, S. (2018). Cardiac Autonomic Neuropathy in Diabetes Mellitus. Methodist DeBakey Cardiovascular Journal, 14(4), 251. doi:10.14797/mdcj-14-4-251Valensi, P., Pariès, J., & Attali, J. . (2003). Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications—the french multicenter study. Metabolism, 52(7), 815-820. doi:10.1016/s0026-0495(03)00095-7Tesfaye, S., Boulton, A. J. M., Dyck, P. J., Freeman, R., Horowitz, M., … Kempler, P. (2010). Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. Diabetes Care, 33(10), 2285-2293. doi:10.2337/dc10-1303Benjamini, Y., & Hochberg, Y. (1995). Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society: Series B (Methodological), 57(1), 289-300. doi:10.1111/j.2517-6161.1995.tb02031.xAdler, G. K., Bonyhay, I., Failing, H., Waring, E., Dotson, S., & Freeman, R. (2008). Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function: Implications for Rigorous Glycemic Control. Diabetes, 58(2), 360-366. doi:10.2337/db08-1153HATHAWAY, D. K., ABELL, T., CARDOSO, S., HARTWIG, M. S., GEBELY, S. E., & Gaber, A. O. (1994). IMPROVEMENT IN AUTONOMIC AND GASTRIC FUNCTION FOLLOWING PANCREAS-KIDNEY VERSUS KIDNEY-ALONE TRANSPLANTATION AND THE CORRELATION WITH QUALITY OF LIFE1,2. Transplantation, 57(6), 816-822. doi:10.1097/00007890-199403270-00008Arnold, R., Pussell, B. A., Pianta, T. J., Lin, C. S.-Y., Kiernan, M. C., & Krishnan, A. V. (2013). Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients. American Journal of Transplantation, 13(9), 2426-2432. doi:10.1111/ajt.12324Vinik, A. I., Maser, R. E., Mitchell, B. D., & Freeman, R. (2003). Diabetic Autonomic Neuropathy. Diabetes Care, 26(5), 1553-1579. doi:10.2337/diacare.26.5.1553Suarez, G. A. (2005). Sudden cardiac death in diabetes mellitus: risk factors in the Rochester diabetic neuropathy study. Journal of Neurology, Neurosurgery & Psychiatry, 76(2), 240-245. doi:10.1136/jnnp.2004.039339Dinh, W., Füth, R., Lankisch, M., Bansemir, L., Nickl, W., Scheffold, T., … Ziegler, D. (2010). Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with Type 2 diabetes and impaired glucose tolerance undergoing coronary angiography. Diabetic Medicine, no-no. doi:10.1111/j.1464-5491.2010.03221.xWackers, F. J. T., Young, L. H., Inzucchi, S. E., Chyun, D. A., Davey, J. A., Barrett, E. J., … Iskandrian, A. E. (2004). Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects: The DIAD study. Diabetes Care, 27(8), 1954-1961. doi:10.2337/diacare.27.8.1954Astrup, A. S., Tarnow, L., Rossing, P., Hansen, B. V., Hilsted, J., & Parving, H.-H. (2006). Cardiac Autonomic Neuropathy Predicts Cardiovascular Morbidity and Mortality in Type 1 Diabetic Patients With Diabetic Nephropathy. Diabetes Care, 29(2), 334-339. doi:10.2337/diacare.29.02.06.dc05-1242Pop-Busui, R., Evans, G. W., Gerstein, H. C., Fonseca, V., Fleg, J. L., … Hoogwerf, B. J. (2010). Effects of Cardiac Autonomic Dysfunction on Mortality Risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial. Diabetes Care, 33(7), 1578-1584. doi:10.2337/dc10-0125Kempler, P., Tesfaye, S., Chaturvedi, N., Stevens, L. K., Webb, D. J., … Eaton, S. (2002). Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabetic Medicine, 19(11), 900-909. doi:10.1046/j.1464-5491.2002.00821.xPop-Busui, R., Cleary, P. A., Braffett, B. H., Martin, C. L., Herman, W. H., Low, P. A., … Bluemke, D. A. (2013). Association Between Cardiovascular Autonomic Neuropathy and Left Ventricular Dysfunction. Journal of the American College of Cardiology, 61(4), 447-454. doi:10.1016/j.jacc.2012.10.02

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features.

Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83 y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPV-associated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPV-associated HSIL

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe

A Basal Sauropodomorph (Dinosauria: Saurischia) from the Ischigualasto Formation (Triassic, Carnian) and the Early Evolution of Sauropodomorpha

BACKGROUND: The earliest dinosaurs are from the early Late Triassic (Carnian) of South America. By the Carnian the main clades Saurischia and Ornithischia were already established, and the presence of the most primitive known sauropodomorph Saturnalia suggests also that Saurischia had already diverged into Theropoda and Sauropodomorpha. Knowledge of Carnian sauropodomorphs has been restricted to this single species. METHODOLOGY/PRINCIPAL FINDINGS: We describe a new small sauropodomorph dinosaur from the Ischigualsto Formation (Carnian) in northwest Argentina, Panphagia protos gen. et sp. nov., on the basis of a partial skeleton. The genus and species are characterized by an anteroposteriorly elongated fossa on the base of the anteroventral process of the nasal; wide lateral flange on the quadrate with a large foramen; deep groove on the lateral surface of the lower jaw surrounded by prominent dorsal and ventral ridges; bifurcated posteroventral process of the dentary; long retroarticular process transversally wider than the articular area for the quadrate; oval scars on the lateral surface of the posterior border of the centra of cervical vertebrae; distinct prominences on the neural arc of the anterior cervical vertebra; distal end of the scapular blade nearly three times wider than the neck; scapular blade with an expanded posterodistal corner; and medial lamina of brevis fossa twice as wide as the iliac spine. CONCLUSIONS/SIGNIFICANCE: We regard Panphagia as the most basal sauropodomorph, which shares the following apomorphies with Saturnalia and more derived sauropodomorphs: basally constricted crowns; lanceolate crowns; teeth of the anterior quarter of the dentary higher than the others; and short posterolateral flange of distal tibia. The presence of Panphagia at the base of the early Carnian Ischigualasto Formation suggests an earlier origin of Sauropodomorpha during the Middle Triassic

The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium

[EN] Fruits and seeds are the major food source on earth. Both derive from the gynoecium and, therefore, it is crucial to understand the mechanisms that guide the development of this organ of angiosperm species. In Arabidopsis, the gynoecium is composed of two congenitally fused carpels, where two domains: medial and lateral, can be distinguished. The medial domain includes the carpel margin meristem (CMM) that is key for the production of the internal tissues involved in fertilization, such as septum, ovules, and transmitting tract. Interestingly, the medial domain shows a high cytokinin signaling output, in contrast to the lateral domain, where it is hardly detected. While it is known that cytokinin provides meristematic properties, understanding on the mechanisms that underlie the cytokinin signaling pattern in the young gynoecium is lacking. Moreover, in other tissues, the cytokinin pathway is often connected to the auxin pathway, but we also lack knowledge about these connections in the young gynoecium. Our results reveal that cytokinin signaling, that can provide meristematic properties required for CMM activity and growth, is enabled by the transcription factor SPATULA (SPT) in the medial domain. Meanwhile, cytokinin signaling is confined to the medial domain by the cytokinin response repressor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFERASE 6 (AHP6), and perhaps by ARR16 (a type-A ARR) as well, both present in the lateral domains (presumptive valves) of the developing gynoecia. Moreover, SPT and cytokinin, probably together, promote the expression of the auxin biosynthetic gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 (TAA1) and the gene encoding the auxin efflux transporter PIN-FORMED 3 (PIN3), likely creating auxin drainage important for gynoecium growth. This study provides novel insights in the spatiotemporal determination of the cytokinin signaling pattern and its connection to the auxin pathway in the young gynoecium.IRO, VMZM, HHU and PLS were supported by the Mexican National Council of Science and Technology (CONACyT) with a PhD fellowship (210085, 210100, 243380 and 219883, respectively). Work in the SDF laboratory was financed by the CONACyT grants CB-2012-177739, FC-2015-2/1061, and INFR-2015-253504, and NMM by the CONACyT grant CB-2011-165986. SDF, CF and LC acknowledge the support of the European Union FP7-PEOPLE-2009-IRSES project EVOCODE (grant no. 247587) and H2020-MSCARISE-2015 project ExpoSEED (grant no. 691109). SDF also acknowledges the Marine Biological Laboratory (MBL) in Woods Hole for a scholarship for the Gene Regulatory Networks for Development Course 2015 (GERN2015). IE acknowledges the International European Fellowship-METMADS project and the Universita degli Studi di Milano (RTD-A; 2016). Research in the laboratory of MFY was funded by NSF (grant IOS-1121055), NIH (grant 1R01GM112976-01A1) and the Paul D. Saltman Endowed Chair in Science Education (MFY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Reyes Olalde, J.; Zuñiga, V.; Serwatowska, J.; Chávez Montes, R.; Lozano-Sotomayor, P.; Herrera-Ubaldo, H.; Gonzalez Aguilera, K.... (2017). The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium. PLoS Genetics. 13(4):1-31. https://doi.org/10.1371/journal.pgen.1006726S131134Reyes-Olalde, J. I., Zuñiga-Mayo, V. M., Chávez Montes, R. A., Marsch-Martínez, N., & de Folter, S. (2013). Inside the gynoecium: at the carpel margin. Trends in Plant Science, 18(11), 644-655. doi:10.1016/j.tplants.2013.08.002Alvarez-Buylla, E. 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