Two Trebouxia algae with different physiological performances are ever-present in lichen thalli of Ramalina farinacea. Coexistence versus Competition

Ramalina farinacea is an epiphytic fruticose lichen that is relatively abundant in areas with Mediterranean, subtropical or temperate climates. Little is known about photobiont diversity in different lichen populations. The present study examines the phycobiont composition of several geographically distant populations of R. farinacea from the Iberian Peninsula, Canary Islands and California as well as the physiological performance of isolated phycobionts. Based on anatomical observations and molecular analyses, the coexistence of two different taxa of Trebouxia (working names, TR1 and TR9) was determined within each thallus of R. farinacea in all of the analysed populations. Examination of the effects of temperature and light on growth and photosynthesis indicated a superior performance of TR9 under relatively high temperatures and irradiances while TR1 thrived at moderate temperature and irradiance. Ramalina farinacea thalli apparently represent a specific and selective form of symbiotic association involving the same two Trebouxia phycobionts. Strict preservation of this pattern of algal coexistence is likely favoured by the different and probably complementary ecophysiological responses of each phycobiont, thus facilitating the proliferation of this lichen in a wide range of habitats and geographic areas. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.This study was funded by the Spanish Ministry of Education and Science (CGL2006-12917-C02-01/02), the Spanish Ministry of Science and Innovation (CGL2009-13429-C02-01/02), the AECID (PCI_A/024755/09) and the Generalitat Valenciana (PROMETEO 174/2008 GVA). We are grateful to Dr J. Gimeno-Romeu (University of California, Davis, USA) and to Dr P. J. G. de Nova (IREC, Ciudad Real, Spain), who were the first to isolate DNA from Ramalina farinacea thalli in our group. Wendy Ran revised the manuscript in English.Casano, L.; Del Campo, E.; García Breijo, FJ.; Reig Armiñana, J.; Gasulla, F.; Del Hoyo, A.; Guéra, A.... (2011). Two Trebouxia algae with different physiological performances are ever-present in lichen thalli of Ramalina farinacea. Coexistence versus Competition. Environmental Microbiology. 13(3):806-818. https://doi.org/10.1111/j.1462-2920.2010.02386.xS806818133Angert, A. L., Huxman, T. E., Chesson, P., & Venable, D. L. (2009). Functional tradeoffs determine species coexistence via the storage effect. Proceedings of the National Academy of Sciences, 106(28), 11641-11645. doi:10.1073/pnas.0904512106Baker, N. R., & Oxborough, K. (s. f.). Chlorophyll Fluorescence as a Probe of Photosynthetic Productivity. Advances in Photosynthesis and Respiration, 65-82. doi:10.1007/978-1-4020-3218-9_3Barreno , E. Herrera-Campos , M. García-Breijo , F. Gasulla , F. Reig-Armiñana , J. 2008 Non photosynthetic bacteria associated to cortical structures on Ramalina and Usnea thalli from Mexico http://192.104.39.110/archive/IAL6abstracts.pdfBECK, A., FRIEDL, T., & RAMBOLD, G. (1998). Selectivity of photobiont choice in a defined lichen community: inferences from cultural and molecular studies. New Phytologist, 139(4), 709-720. doi:10.1046/j.1469-8137.1998.00231.xBilger, W., & Bj�rkman, O. (1991). Temperature dependence of violaxanthin de-epoxidation and non-photochemical fluorescence quenching in intact leaves ofGossypium hirsutum L. andMalva parviflora L. Planta, 184(2), 226-234. doi:10.1007/bf01102422Bj�rkman, O., & Demmig, B. (1987). Photon yield of O2 evolution and chlorophyll fluorescence characteristics at 77 K among vascular plants of diverse origins. Planta, 170(4), 489-504. doi:10.1007/bf00402983Bold, H. C., & Parker, B. C. (1962). Some supplementary attributes in the classification of chlorococcum species. Archiv f�r Mikrobiologie, 42(3), 267-288. doi:10.1007/bf00422045Cenis, J. L. (1992). Rapid extraction of fungal DNA for PCR amplification. Nucleic Acids Research, 20(9), 2380-2380. doi:10.1093/nar/20.9.2380Del Campo, E. M., Casano, L. M., Gasulla, F., & Barreno, E. (2010). Suitability of chloroplast LSU rDNA and its diverse group I introns for species recognition and phylogenetic analyses of lichen-forming Trebouxia algae. Molecular Phylogenetics and Evolution, 54(2), 437-444. doi:10.1016/j.ympev.2009.10.024Demmig-Adams, B., & Adams, W. W. (1996). The role of xanthophyll cycle carotenoids in the protection of photosynthesis. Trends in Plant Science, 1(1), 21-26. doi:10.1016/s1360-1385(96)80019-7Demmig-Adams, B., M�guas, C., Adams, W. W., Meyer, A., Kilian, E., & Lange, O. L. (1990). Effect of high light on the efficiency of photochemical energy conversion in a variety of lichen species with green and blue-green phycobionts. Planta, 180(3), 400-409. doi:10.1007/bf01160396DePriest, P. T. (2004). Early Molecular Investigations of Lichen-Forming Symbionts: 1986–2001. Annual Review of Microbiology, 58(1), 273-301. doi:10.1146/annurev.micro.58.030603.123730DOERING, M., & PIERCEY-NORMORE, M. D. (2009). Genetically divergent algae shape an epiphytic lichen community on Jack Pine in Manitoba. The Lichenologist, 41(1), 69-80. doi:10.1017/s0024282909008111Friedl, T. (1989). Comparative ultrastructure of pyrenoids inTrebouxia (Microthamniales, Chlorophyta). Plant Systematics and Evolution, 164(1-4), 145-159. doi:10.1007/bf00940435Gasulla, F., de Nova, P. G., Esteban-Carrasco, A., Zapata, J. M., Barreno, E., & Guéra, A. (2009). Dehydration rate and time of desiccation affect recovery of the lichenic algae Trebouxia erici: alternative and classical protective mechanisms. Planta, 231(1), 195-208. doi:10.1007/s00425-009-1019-yGasulla, F., Guéra, A., & Barreno, E. (2010). “A simple and rapid method for isolating lichen photobionts“. Symbiosis, 51(2), 175-179. doi:10.1007/s13199-010-0064-4Gauze, G. F. (1934). The struggle for existence, by G. F. Gause. doi:10.5962/bhl.title.4489Genty, B., Briantais, J.-M., & Baker, N. R. (1989). The relationship between the quantum yield of photosynthetic electron transport and quenching of chlorophyll fluorescence. Biochimica et Biophysica Acta (BBA) - General Subjects, 990(1), 87-92. doi:10.1016/s0304-4165(89)80016-9Gross, K. (2008). Positive interactions among competitors can produce species-rich communities. Ecology Letters, 11(9), 929-936. doi:10.1111/j.1461-0248.2008.01204.xGUZOW-KRZEMIŃSKA, B. (2006). Photobiont flexibility in the lichen Protoparmeliopsis muralis as revealed by ITS rDNA analyses. The Lichenologist, 38(5), 469-476. doi:10.1017/s0024282906005068Haruta, S., Kato, S., Yamamoto, K., & Igarashi, Y. (2009). Intertwined interspecies relationships: approaches to untangle the microbial network. Environmental Microbiology, 11(12), 2963-2969. doi:10.1111/j.1462-2920.2009.01956.xJOHANSEN, S., & HAUGEN, P. (2001). A new nomenclature of group I introns in ribosomal DNA. RNA, 7(7), 935-936. doi:10.1017/s1355838201010500Jones, A. ., Berkelmans, R., van Oppen, M. J. ., Mieog, J. ., & Sinclair, W. (2008). A community change in the algal endosymbionts of a scleractinian coral following a natural bleaching event: field evidence of acclimatization. Proceedings of the Royal Society B: Biological Sciences, 275(1641), 1359-1365. doi:10.1098/rspb.2008.0069Kopecky, J., Azarkovich, M., Pfündel, E. E., Shuvalov, V. A., & Heber, U. (2005). Thermal Dissipation of Light Energy is Regulated Differently and by Different Mechanisms in Lichens and Higher Plants. Plant Biology, 7(2), 156-167. doi:10.1055/s-2005-837471Kosugi, M., Arita, M., Shizuma, R., Moriyama, Y., Kashino, Y., Koike, H., & Satoh, K. (2009). Responses to Desiccation Stress in Lichens are Different from Those in Their Photobionts. Plant and Cell Physiology, 50(4), 879-888. doi:10.1093/pcp/pcp043Kranner, I., Cram, W. J., Zorn, M., Wornik, S., Yoshimura, I., Stabentheiner, E., & Pfeifhofer, H. W. (2005). Antioxidants and photoprotection in a lichen as compared with its isolated symbiotic partners. Proceedings of the National Academy of Sciences, 102(8), 3141-3146. doi:10.1073/pnas.0407716102Kroken, S., & Taylor, J. W. (2000). Phylogenetic Species, Reproductive Mode, and Specificity of the Green AlgaTrebouxiaForming Lichens with the Fungal GenusLetharia. The Bryologist, 103(4), 645-660. doi:10.1639/0007-2745(2000)103[0645:psrmas]2.0.co;2Little, A. F. (2004). Flexibility in Algal Endosymbioses Shapes Growth in Reef Corals. Science, 304(5676), 1492-1494. doi:10.1126/science.1095733Loarie, S. R., Duffy, P. B., Hamilton, H., Asner, G. P., Field, C. B., & Ackerly, D. D. (2009). The velocity of climate change. Nature, 462(7276), 1052-1055. doi:10.1038/nature08649Muggia, L., Grube, M., & Tretiach, M. (2008). Genetic diversity and photobiont associations in selected taxa of the Tephromela atra group (Lecanorales, lichenised Ascomycota). Mycological Progress, 7(3), 147-160. doi:10.1007/s11557-008-0560-6Niyogi, K. K. (2004). Is PsbS the site of non-photochemical quenching in photosynthesis? Journal of Experimental Botany, 56(411), 375-382. doi:10.1093/jxb/eri056O’Brien, H. E., Miadlikowska, J., & Lutzoni, F. (2005). Assessing host specialization in symbiotic cyanobacteria associated with four closely related species of the lichen fungusPeltigera. European Journal of Phycology, 40(4), 363-378. doi:10.1080/09670260500342647Ohmura, Y., Kawachi, M., Kasai, F., Watanabe, M. M., & Takeshita, S. (2006). Genetic combinations of symbionts in a vegetatively reproducing lichen,Parmotrema tinctorum, based on ITS rDNA sequences. The Bryologist, 109(1), 43-59. doi:10.1639/0007-2745(2006)109[0043:gcosia]2.0.co;2Piercey-Normore, M. D. (2005). The lichen-forming ascomyceteEvernia mesomorphaassociates with multiple genotypes ofTrebouxia jamesii. New Phytologist, 169(2), 331-344. doi:10.1111/j.1469-8137.2005.01576.xPombert, J.-F., Lemieux, C., & Turmel, M. (2006). BMC Biology, 4(1), 3. doi:10.1186/1741-7007-4-3Rambold, G., Friedl, T., & Beck, A. (1998). Photobionts in Lichens: Possible Indicators of Phylogenetic Relationships? The Bryologist, 101(3), 392. doi:10.1639/0007-2745(1998)101[392:pilpio]2.0.co;2Romeike, J., Friedl, T., Helms, G., & Ott, S. (2002). Genetic Diversity of Algal and Fungal Partners in Four Species of Umbilicaria (Lichenized Ascomycetes) Along a Transect of the Antarctic Peninsula. Molecular Biology and Evolution, 19(8), 1209-1217. doi:10.1093/oxfordjournals.molbev.a004181Rosenberg, E., Sharon, G., & Zilber-Rosenberg, I. (2009). The hologenome theory of evolution contains Lamarckian aspects within a Darwinian framework. Environmental Microbiology, 11(12), 2959-2962. doi:10.1111/j.1462-2920.2009.01995.xSchreiber, U., Schliwa, U., & Bilger, W. (1986). Continuous recording of photochemical and non-photochemical chlorophyll fluorescence quenching with a new type of modulation fluorometer. Photosynthesis Research, 10(1-2), 51-62. doi:10.1007/bf00024185Skaloud, P., & Peksa, O. (2010). Evolutionary inferences based on ITS rDNA and actin sequences reveal extensive diversity of the common lichen alga Asterochloris (Trebouxiophyceae, Chlorophyta). Molecular Phylogenetics and Evolution, 54(1), 36-46. doi:10.1016/j.ympev.2009.09.035Wegley, L., Edwards, R., Rodriguez-Brito, B., Liu, H., & Rohwer, F. (2007). Metagenomic analysis of the microbial community associated with the coral Porites astreoides. Environmental Microbiology, 9(11), 2707-2719. doi:10.1111/j.1462-2920.2007.01383.xWeis, E., & Berry, J. A. (1987). Quantum efficiency of Photosystem II in relation to ‘energy’-dependent quenching of chlorophyll fluorescence. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 894(2), 198-208. doi:10.1016/0005-2728(87)90190-3Wornik, S., & Grube, M. (2009). Joint Dispersal Does Not Imply Maintenance of Partnerships in Lichen Symbioses. Microbial Ecology, 59(1), 150-157. doi:10.1007/s00248-009-9584-yYAHR, R., VILGALYS, R., & DEPRIEST, P. T. (2004). Strong fungal specificity and selectivity for algal symbionts in Florida scrub Cladonia lichens. Molecular Ecology, 13(11), 3367-3378. doi:10.1111/j.1365-294x.2004.02350.xYahr, R., Vilgalys, R., & DePriest, P. T. (2006). Geographic variation in algal partners of Cladonia subtenuis (Cladoniaceae) highlights the dynamic nature of a lichen symbiosis. New Phytologist, 171(4), 847-860. doi:10.1111/j.1469-8137.2006.01792.xZoller, S. (2003). Slow algae, fast fungi: exceptionally high nucleotide substitution rate differences between lichenized fungi Omphalina and their symbiotic green algae Coccomyxa. Molecular Phylogenetics and Evolution, 29(3), 629-640. doi:10.1016/s1055-7903(03)00215-

Discovery of novel CSF biomarkers to predict progression in dementia using machine learning

Providing an accurate prognosis for individual dementia patients remains a challenge since they greatly differ in rates of cognitive decline. In this study, we used machine learning techniques with the aim to identify cerebrospinal fluid (CSF) biomarkers that predict the rate of cognitive decline within dementia patients. First, longitudinal mini-mental state examination scores (MMSE) of 210 dementia patients were used to create fast and slow progression groups. Second, we trained random forest classifiers on CSF proteomic profiles and obtained a well-performing prediction model for the progression group (ROC-AUC = 0.82). As a third step, Shapley values and Gini feature importance measures were used to interpret the model performance and identify top biomarker candidates for predicting the rate of cognitive decline. Finally, we explored the potential for each of the 20 top candidates in internal sensitivity analyses. TNFRSF4 and TGF [Formula: see text]-1 emerged as the top markers, being lower in fast-progressing patients compared to slow-progressing patients. Proteins of which a low concentration was associated with fast progression were enriched for cell signalling and immune response pathways. None of our top markers stood out as strong individual predictors of subsequent cognitive decline. This could be explained by small effect sizes per protein and biological heterogeneity among dementia patients. Taken together, this study presents a novel progression biomarker identification framework and protein leads for personalised prediction of cognitive decline in dementia

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice : A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads