Habitat is more important than climate for structuring soil fungal communities associated in truffle sites.

The ectomycorrhizal fungi Tuber melanosporum Vittad. and Tuber aestivum Vittad. produce highly valuable truffles, but little is known about the soil fungal communities associated with these truffle species in places where they co-occur. Here, we compared soil fungal communities present in wild and planted truffle sites, in which T. melanosporum and T. aestivum coexist, in Mediterranean and temperate regions over three sampling seasons spanning from 2018 to 2019. We showed that soil fungal community composition and ectomycorrhizal species composition are driven by habitat type rather than climate regions. Also, we observed the influence of soil pH, organic matter content and C:N ratio structuring total and ectomycorrhizal fungal assemblages. Soil fungal communities in wild sites revealed more compositional variability than those of plantations. Greater soil fungal diversity was found in temperate compared to Mediterranean sites when considering all fungal guilds. Ectomycorrhizal diversity was significantly higher in wild sites compared to plantations. Greater mould abundance at wild sites than those on plantation was observed while tree species and seasonal effects were not significant predictors in fungal community structure. Our results suggested a strong influence of both ecosystem age and management on the fungal taxa composition in truffle habitats.

Test for abnormal niacin response syndrome in schizophrenia: reclaiming the oral route / Prueba de síndrome de respuesta a niacina anormal en pacientes con diagnóstico de esquizofrenia: reivindicando la vía oral.

Introduction: Although there is an abnormal presentation of Niacin Response Syndrome (ANRS) in schizophrenic patients (SZ) compared to subjects with other psychiatric illnesses and with healthy individuals. However, most of the literature is based on studies that have used tests of niacin topical administration, observing, on the other hand, less scientific production of its oral administration. The objective was to determine the sensitivity of the oral niacin test as a method of detecting ASRN in EZ. Methods: A non-randomized clinical trial was carried out. Two groups were formed, the experimental or SZ, with 21 patients diagnosed with schizophrenia according to DSM-IV-TR SZ or schizoaffective disorder, and the HC group, made up of 20 healthy controls. Both groups were exposed to an oral niacin test and clinical-semiological tools were applied to evaluate the NRS. Results: 90.5% of the SZ group presented ANRS. In contrast, no participant in the HC group presented ANRS (0%). Conclusions: Oral niacin administration was sensitive to the detection of ASRN in schizophrenia. Likewise, ASRN could be a gradual phenomenon and its prevalence could be dose-dependent, being lower the lower the dose of oral niacin used. Further trials with larger and randomized samples will be needed.

Introducción: En pacientes esquizofrénicos (EZ) existe un síndrome de respuesta a niacina (ASRN) anormal en comparación con sujetos con otras enfermedades psiquiátricas y con individuos sanos. Sin embargo, la mayor parte de la literatura se basa en estudios que han utilizado pruebas de niacina por vía tópica, observándose, en cambio, menor cantidad de ensayos utilizando su administración por vía oral, a pesar de existir algunas ventajas comparativas con el uso de esta última vía. El objetivo fue determinar la sensibilidad de la prueba de niacina por vía oral como método de detección del ASRN en EZ. Metodología: Se realizó un ensayo clínico no aleatorizado, conformando dos grupos, el grupo experimental o EZ, con 21 pacientes con diagnóstico de esquizofrenia según DSM-IV-TR SZ o trastorno esquizoafectivo, y el grupo CS, constituido por 20 controles sanos. Ambos grupos fueron expuestos a la prueba de niacina por vía oral y se aplicaron herramientas clínico-semiológicas para evaluar el SRN. Resultados: La prevalencia de ASRN fue del 90,5% en el grupo EZ, mientras que en el grupo CS fue nula (0%). Conclusiones: La administración oral de niacina fue sensible a la detección de ASRN en la esquizofrenia. Asimismo, la ASRN podría ser un fenómeno gradual y su prevalencia podría ser dosis-dependiente, siendo menor cuanto menor sea la dosis de niacina oral utilizada. Se necesitarán ensayos adicionales con muestras de mayor tamaño y aleatorizadas.

Silvicultural management and altitude prevail on soil properties and fungal community in shaping understorey plant communities in a Mediterranean pine forest.

Understorey vegetation plays a key role in Mediterranean forest ecosystem functioning. However, we still lack a thorough understanding of the patterns and drivers of understorey composition and diversity. As a result, understoreys are often ignored during assessments of forest functioning under climate change. Here we studied the effect of silvicultural management, topography, soil fungal community composition and soil physical and chemical properties on understorey community composition and diversity. The plant cover and number of individuals of understorey perennial plants, shrubs and non-dominant trees was recorded on 24 plots (paired: control-thinned) in a Mediterranean pine-dominated mountainous area in Northeast Spain. The study area represented a broad thinning intensity gradient (from 0 to 70 % in removed stand basal area) along a 400-m altitudinal range (from 609 m to 1013 m). Our results showed that thinning intensity and topography explained the greatest proportion of the total variance in the understorey species composition, i.e., 18 % and 16 %, respectively. Interestingly, the effects of the silvicultural treatments were significant only when considering the altitudinal effect, so that, the main impacts of thinning on the understorey community composition occurred at low altitudes (between 609 m and 870 m). Moreover, we found a significant decrease in both richness and abundance of understorey species in both the control and thinned plots with increasing altitude, with thinned plots being significantly richer in species compared to the control plots. The difference in the understorey community sensitivity to forest thinning along the altitudinal gradient suggests changes in factors that limit plant growth. Low elevation plots were restrained by light availability while high altitudes plots limited by winter freezing temperature.

The fall of the summer truffle: Recurring hot, dry summers result in declining fruitbody production of Tuber aestivum in Central Europe.

Global warming is pushing populations outside their range of physiological tolerance. According to the environmental envelope framework, the most vulnerable populations occur near the climatic edge of their species' distributions. In contrast, populations from the climatic center of the species range should be relatively buffered against climate warming. We tested this latter prediction using a combination of linear mixed effects and machine learning algorithms on an extensive, citizen-scientist generated dataset on the fruitbody productivity of the Burgundy (aka summer) truffle (Tuber aestivum Vittad.), a keystone, ectomycorrhizal tree-symbiont occurring on a wide range of temperate climates. T. aestivum's fruitbody productivity was monitored at 3-week resolution over up to 8 continuous years at 20 sites distributed in the climatic center of its European distribution in southwest Germany and Switzerland. We found that T. aestivum fruitbody production is more sensitive to summer drought than would be expected from the breadth of its species' climatic niche. The monitored populations occurring nearly 5°C colder than the edge of their species' climatic distribution. However, interannual fruitbody productivity (truffle mass year-1 ) fell by a median loss of 22% for every 1°C increase in summer temperature over a site's 30-year mean. Among the most productive monitored populations, the temperature sensitivity was even higher, with single summer temperature anomalies of 3°C sufficient to stop fruitbody production altogether. Interannual truffle productivity was also related to the phenology of host trees, with ~22 g less truffle mass for each 1-day reduction in the length of the tree growing season. Increasing summer drought extremes are therefore likely to reduce fruiting among summer truffle populations throughout Central Europe. Our results suggest that European T. aestivum may be a mosaic of vulnerable populations, sensitive to climate-driven declines at lower thresholds than implied by its species distribution model.

Vitamin D: Between the brightness of the sun and the darkness of depression.

INTRODUCTION: The scientific literature suggests a relationship between vitamin D (VitD) and the onset, treatment and prognosis of depression. However, this line of research continues to be controversial. The aim of the study was to analyse the relationship between depression and VitD values, controlling for the influence of the season. MATERIAL AND METHODS: Observational and cross-sectional study. The sample was made up of 150 adult female volunteer participants (aged between 28 and 78 years). The sample was stratified into three groups: a) depression without treatment, b) depression under treatment with antidepressants, and c) without depression (control). VitD values (ng/ml) were compared. RESULTS: Significant differences were found between the three groups surveyed. The group of participants with depression without treatment obtained the lowest VitD values (mean 18.62ng/ml; SD 8.42), compatible with severe insufficiency. The group of participants with depression in treatment obtained higher values than the previous group, although in an insufficient range (mean 23.80ng/ml; SD 11.30). The third group (control) obtained the highest values and in accordance with the desirable range (mean 30.19ng/ml; SD 10.21). There were no age differences between the groups. When controlling for possible effects of the season, the previous differences in VitD between the three groups were maintained, with an evident decrease of all the mean levels in the winter period. CONCLUSIONS: Depression is associated with insufficient VitD values. Treatment with antidepressants improves these values, although they continue to be insufficient. The findings of this study reinforce the evidence for an association between depression and VitD.

Termite sensitivity to temperature affects global wood decay rates.

Deadwood is a large global carbon store with its store size partially determined by biotic decay. Microbial wood decay rates are known to respond to changing temperature and precipitation. Termites are also important decomposers in the tropics but are less well studied. An understanding of their climate sensitivities is needed to estimate climate change effects on wood carbon pools. Using data from 133 sites spanning six continents, we found that termite wood discovery and consumption were highly sensitive to temperature (with decay increasing >6.8 times per 10°C increase in temperature)-even more so than microbes. Termite decay effects were greatest in tropical seasonal forests, tropical savannas, and subtropical deserts. With tropicalization (i.e., warming shifts to tropical climates), termite wood decay will likely increase as termites access more of Earth's surface.

Vitamina D: entre el brillo del sol y la oscuridad de la depresión / Vitamin D: Between the Brightness of the sun and the Darkness of Depression

RESUMEN Introducción: La literatura científica indica que hay relación entre la vitamina D (VitD) y el inicio, el tratamiento y el pronóstico de la depresión. Sin embargo, esta línea de investigación continúa siendo motivo de controversia. El propósito del trabajo es analizar la relación entre la depresión y los valores de VitD, controlando por la influencia de la estación. Material y métodos: Estudio observacional y transversal. La muestra quedó conformada por 150 voluntarias adultas (edad, 28-78 arios). Se estratificó la muestra en 3 grupos: depresión sin tratamiento, depresión en tratamiento con antidepresivos y sin depresión (control). Se compararon los valores de VitD. Resultados: Se hallaron diferencias significativas entre los 3 grupos de comparación. El grupo con depresión sin tratamiento obtuvo los valores de VitD más bajos (media, 18,62 ± 8,42 ng/ml), compatibles con una insuficiencia grave. El grupo de participantes con depresión en tratamiento obtuvo valores más altos que el grupo anterior, aunque en la franja de insufi ciencia (23,80 ± 11,30 ng/ml). El tercer grupo (control) obtuvo los valores más altos y acordes con el intervalo deseable (30,19 ± 10,21 ng/ml). No hubo diferencias de edad entre los grupos. Al controlar por posibles efectos de la estación del año, las diferencias previas de VitD entre los 3 grupos se mantuvieron, con un descenso ostensible de todas las medias en el periodo invernal. Conclusiones: La depresión se asocia con valores de VitD insuficientes. El tratamiento con antidepresivos mejora esos valores, aunque continúan siendo insuficientes. Los hallazgos de este estudio refuerzan la evidencia de una asociación entre la depresión y la VitD.

ABSTRACT Introduction: The scientific literature suggests a relationship between vitamin D (VitD) and the onset, treatment and prognosis of depression. However, this line of research continues to be controversial. The aim of the study was to analyse the relationship between depression and VitD values, controlling for the influence of the season. Material and methods: Observational and cross-sectional study. The sample was made up of 150 adult female volunteer participants (aged between 28 and 78 years). The sample was stratified into three groups: a) depression without treatment, b) depression under treat ment with antidepressants, and c) without depression (control). VitD values (ng/ml) were compared. Results: Significant differences were found between the three groups surveyed. The group of participants with depression without treatment obtained the lowest VitD values (mean 18.62 ng/ml; SD 8.42), compatible with severe insufficiency. The group of participants with depression in treatment obtained higher values than the previous group, although in an insufficient range (mean 23.80 ng/ml; SD 11.30). The third group (control) obtained the hig hest values and in accordance with the desirable range (mean 30.19 ng/ml; SD 10.21). There were no age differences between the groups. When controlling for possible effects of the season, the previous differences in VitD between the three groups were maintained, with an evident decrease of all the mean levels in the winter period. Conclusions: Depression is associated with insufficient VitD values. Treatment with antidepressants improves these values, although they continue to be insufficient. The findings of this study reinforce the evidence for an association between depression and VitD.

Reproductive aging and executive functions in healthy women.

The aim of this study was to analyze the influence of reproductive aging on executive functions. We assessed executive functions in three groups of healthy women in the premenopausal (n = 45, mean age = 30.89, SD = 10.5), perimenopausal (n = 31, mean age = 50.06, SD = 3.6) and postmenopausal (n = 24, mean age = 63.39, SD = 6.5) phase. No differences between groups were observed in working memory, verbal fluency, inhibitory control, planning, and cognitive flexibility. However, when the analyses were repeated with participants with occupations with lower intellectual demands, perimenopausal and postmenopausal women performed worse than premenopausal women in semantic verbal fluency. This study provides important evidence to understand the effects of reproductive aging on cognitive performance in healthy women. Our findings indicate that cognitive reserve-related factors may be important to understand the differences in executive functions associated with reproductive aging.

DeepMP: a deep learning tool to detect DNA base modifications on Nanopore sequencing data.

MOTIVATION: DNA methylation plays a key role in a variety of biological processes. Recently, Nanopore long-read sequencing has enabled direct detection of these modifications. As a consequence, a range of computational methods have been developed to exploit Nanopore data for methylation detection. However, current approaches rely on a human-defined threshold to detect the methylation status of a genomic position and are not optimized to detect sites methylated at low frequency. Furthermore, most methods use either the Nanopore signals or the basecalling errors as the model input and do not take advantage of their combination. RESULTS: Here, we present DeepMP, a convolutional neural network-based model that takes information from Nanopore signals and basecalling errors to detect whether a given motif in a read is methylated or not. Besides, DeepMP introduces a threshold-free position modification calling model sensitive to sites methylated at low frequency across cells. We comprehensively benchmarked DeepMP against state-of-the-art methods on Escherichia coli, human and pUC19 datasets. DeepMP outperforms current approaches at read-based and position-based methylation detection across sites methylated at different frequencies in the three datasets. AVAILABILITY AND IMPLEMENTATION: DeepMP is implemented and freely available under MIT license at https://github.com/pepebonet/DeepMP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Functional capacity and cognitive performance of adults from Argentina in cardiopulmonary rehabilitation / Capacidad funcional y rendimiento cognitivo de adultos argentinos en rehabilitación cardiopulmonar.

Introduction: Functional capacity is decreased in people with Cardiovascular Diseases and Chronic Respiratory Diseases. These diseases have also been associated with cognitive dysfunction. The study examines the efficacy of a cardiopulmonary rehabilitation program in the recovery of functional capacity and analyzes whether subjects with cardiopulmonary diseases suffer from cognitive dysfunction. Materials and methods: Participated 50 adults with medium-high education who completed a cardiopulmonary rehabilitation program of between 3 and 6 months based on physical education, nutritional education, promotion of healthy habits and medication management. Functional capacity was evaluated with the Duke index at the beginning and end of the program. Memory and language tests were also administered, for the only time, at the beginning of the program, comparing the values obtained with Argentine normative studies. The data was analyzed with the Wilcoxon test, bivariate correlations, and linear regression. Results: Functional capacity increased significantly at the end of the program. In any case, the post-program Duke value suggests that the functional capacity of the patients continues to be affected. On the other hand, a memory test explained 10,8% of the variance in the Duke index, and there are no findings of cognitive dysfunction. Conclusion: The functional capacity of cardiopulmonary patients improved with the rehabilitation program, although this improvement is clinically insufficient. Better memory performance predicted greater functional capacity, which is why it is suggested to add cognitive stimulation workshops to cardiopulmonary rehabilitation programs. This sample with cardiopulmonary disease does not present cognitive dysfunction, probably due to its high cognitive reserve. Introduction: Functional capacity is decreased in people with Cardiovascular Diseases and Chronic Respiratory Diseases. These diseases have also been associated with cognitive dysfunction. The study examines the efficacy of a cardiopulmonary rehabilitation program in the recovery of functional capacity and analyzes whether subjects with cardiopulmonary diseases suffer from cognitive dysfunction. Materials and methods: Participated 50 adults with medium-high education who completed a cardiopulmonary rehabilitation program of between 3 and 6 months based on physical education, nutritional education, promotion of healthy habits and medication management. Functional capacity was evaluated with the Duke index at the beginning and end of the program. Memory and language tests were also administered, for the only time, at the beginning of the program, comparing the values obtained with Argentine normative studies. The data was analyzed with the Wilcoxon test, bivariate correlations, and linear regression. Results: Functional capacity increased significantly at the end of the program. In any case, the post-program Duke value suggests that the functional capacity of the patients continues to be affected. On the other hand, a memory test explained 10,8% of the variance in the Duke index, and there are no findings of cognitive dysfunction. Conclusion: The functional capacity of cardiopulmonary patients improved with the rehabilitation program, although this improvement is clinically insufficient. Better memory performance predicted greater functional capacity, which is why it is suggested to add cognitive stimulation workshops to cardiopulmonary rehabilitation programs. This sample with cardiopulmonary disease does not present cognitive dysfunction, probably due to its high cognitive reserve.

Introducción: La capacidad funcional está disminuida en personas con Enfermedades Cardiovasculares y Enfermedades Respiratorias Crónicas. Estas enfermedades también han sido asociadas a disfunción cognitiva. El estudio examina la eficacia de un programa de rehabilitación cardiopulmonar en la recuperación de la capacidad funcional, y analiza si sujetos con enfermedades cardiopulmonares sufren disfunción cognitiva. Materiales y métodos: Participaron 50 personas adultas con instrucción media-alta que completaron un programa de rehabilitación cardiopulmonar de entre 3 y 6 meses basado en educación física, educación nutricional, promoción de hábitos saludables y manejo de medicación. Se evaluó la capacidad funcional con el índice Duke al iniciar y finalizar el programa. Se administró también, por única vez, al iniciar el programa, pruebas de memoria y de lenguaje, comparando los valores obtenidos con estudios normativos argentinos. Se analizó los datos con test Wilcoxon, correlaciones bivariadas y regresión lineal. Resultados: La capacidad funcional aumentó significativamente al finalizar el programa. De todos modos el valor Duke pos- programa sugiere que la capacidad funcional de los pacientes continúa afectada. Por otro lado, una prueba de memoria explicó el 10,8% de la varianza en el índice Duke, y no hay hallazgos de disfunción cognitiva. Conclusión: La capacidad funcional de los pacientes cardiopulmonares mejoró con el programa de rehabilitación, aunque dicha mejora, es clínicamente insuficiente. Mejor rendimiento de memoria predijo mayor capacidad funcional, por lo que se sugiere añadir talleres de estimulación cognitiva a los programas de rehabilitación cardiopulmonares. Esta muestra con enfermedad cardiopulmonar no presenta disfunción cognitiva, probablemente por su elevada reserva cognitiva.

Lack of Phylogenetic Differences in Ectomycorrhizal Fungi among Distinct Mediterranean Pine Forest Habitats.

Understanding whether the occurrences of ectomycorrhizal species in a given tree host are phylogenetically determined can help in assessing different conservational needs for each fungal species. In this study, we characterized ectomycorrhizal phylogenetic composition and phylogenetic structure in 42 plots with five different Mediterranean pine forests: i.e., pure forests dominated by P. nigra, P. halepensis, and P. sylvestris, and mixed forests of P. nigra-P. halepensis and P. nigra-P. sylvestris, and tested whether the phylogenetic structure of ectomycorrhizal communities differs among these. We found that ectomycorrhizal communities were not different among pine tree hosts neither in phylogenetic composition nor in structure and phylogenetic diversity. Moreover, we detected a weak abiotic filtering effect (4%), with pH being the only significant variable influencing the phylogenetic ectomycorrhizal community, while the phylogenetic structure was slightly influenced by the shared effect of stand structure, soil, and geographic distance. However, the phylogenetic community similarity increased at lower pH values, supporting that fewer, closely related species were found at lower pH values. Also, no phylogenetic signal was detected among exploration types, although short and contact were the most abundant types in these forest ecosystems. Our results demonstrate that pH but not tree host, acts as a strong abiotic filter on ectomycorrhizal phylogenetic communities in Mediterranean pine forests at a local scale. Finally, our study shed light on dominant ectomycorrhizal foraging strategies in drought-prone ecosystems such as Mediterranean forests.

Climate change induced declines in fuel moisture may turn currently fire-free Pyrenean mountain forests into fire-prone ecosystems.

Fuel moisture limits the availability of fuel to wildfires in many forest areas worldwide, but the effects of climate change on moisture constraints remain largely unknown. Here we addressed how climate affects fuel moisture in pine stands from Catalonia, NE Spain, and the potential effects of increasing climate aridity on burned area in the Pyrenees, a mesic mountainous area where fire is currently rare. We first quantified variation in fuel moisture in six sites distributed across an altitudinal gradient where the long-term mean annual temperature and precipitation vary by 6-15 °C and 395-933 mm, respectively. We observed significant spatial variation in live (78-162%) and dead (10-15%) fuel moisture across sites. The pattern of variation was negatively linked (r = |0.6|-|0.9|) to increases in vapor pressure deficit (VPD) and in the Aridity Index. Using seasonal fire records over 2006-2020, we observed that summer burned area in the Mediterranean forests of Northeast Spain and Southern France was strongly dependent on VPD (r = 0.93), the major driver (and predictor) of dead fuel moisture content (DFMC) at our sites. Based on the difference between VPD thresholds associated with large wildfire seasons in the Mediterranean (3.6 kPa) and the maximum VPD observed in surrounding Pyrenean mountains (3.1 kPa), we quantified the "safety margin" for Pyrenean forests (difference between actual VPD and that associated with large wildfires) at 0.5 kPa. The effects of live fuel moisture content (LFMC) on burned area were not significant under current conditions, a situation that may change with projected increases in climate aridity. Overall, our results indicate that DFMC in currently fire-free areas in Europe, like the Pyrenees, with vast amounts of fuel in many forest stands, may reach critical dryness thresholds beyond the safety margin and experience large wildfires after only mild increases in VPD, although LFMC can modulate the response.

Sampling forest soils to describe fungal diversity and composition. Which is the optimal sampling size in mediterranean pure and mixed pine oak forests?

Soil sampling is a critical step affecting perceived fungal diversity, however sampling optimization for high-throughput-DNA sequencing studies have never been tested in Mediterranean forest ecosystems. We identified the minimum number of pooled samples needed to obtain a reliable description of fungal communities in terms of diversity and composition in three different Mediterranean forests (pine, oak, and mixed-pine-oak). Twenty soil samples were randomly selected in each of the three plots per type. Samples obtained in 100 m2 plots were pooled to obtain mixtures of 3, 6, 10, 15, 20 samples, and sequenced using Illumina MiSeq of fungal ITS2 amplicons. Pooling three soil samples in Pinus and Quercus stands provided consistent richness estimations, while at least six samples were needed in mixed-stands. ß-diversity decreased with increasing sample pools in monospecific-stands, while there was no effect of sample pool size on mixed-stands. Soil sample pooling had no effect over species composition. We estimate that three samples would be already optimal to describe fungal richness and composition in Mediterranean pure stands, while at least six samples would be needed in mixed stands.

White mulch and irrigation increase black truffle soil mycelium when competing with summer truffle in young truffle orchards.

The black truffle (Tuber melanosporum Vittad.) and the summer truffle (Tuber aestivum Vittad.) are two of the most appreciated edible fungi worldwide. The natural distributions of both species partially overlap. However, the interspecific interactions between these truffles and how irrigation and mulching techniques impact the dynamics between them are still unknown. Here, an experimental truffle plantation with Quercus ilex was established in Maials (Catalonia, Spain), combining three soil mulch treatments (white mulch, black mulch and bare soil as a control) and two irrigation regimes (irrigated and non-irrigated as a control) to investigate truffle mycelial dynamics in soil when both truffle species co-occur. The development of truffle mycelium in two different seasons (spring and autumn) in two consecutive years (2017 and 2018) was quantified using qPCR. Truffle mycelia of both species showed greatest development under white mulch. When mycelia of both truffle species co-occurred in soil, irrigation combined with white mulch resulted in greater quantities of T. melanosporum mycelial biomass, whereas the control irrigation treatment favoured the development of T. aestivum. Mulch treatments were also advantageous for seedling growth, which was expressed as root collar diameter and its increment during the study period. Significant relationships between root collar diameter and root growth and the amount of mycelial biomass in the soil were observed for both truffle species. Our results indicate the potential advantages of using white mulch to support irrigation in truffle plantations located in areas with dry Mediterranean climatic conditions to promote the development of Tuber mycelium.

The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy.

A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

Production and turnover of mycorrhizal soil mycelium relate to variation in drought conditions in Mediterranean Pinus pinaster, Pinus sylvestris and Quercus ilex forests.

In forests, ectomycorrhizal mycelium is pivotal for driving soil carbon and nutrient cycles, but how ectomycorrhizal mycelial dynamics vary in ecosystems with drought periods is unknown. We quantified the production and turnover of mycorrhizal mycelium in Mediterranean Pinus pinaster, Pinus sylvestris and Quercus ilex forests and related the estimates to standardised precipitation index (SPI), to study how mycelial dynamics relates to tree species and drought-moisture conditions. Production and turnover of mycelium was estimated between July and February, by quantifying the fungal biomass (ergosterol) in ingrowth mesh bags and using statistical modelling. SPI for time scales of 1-3 months was calculated from precipitation records and precipitation data over the study period. Forests dominated by Pinus trees displayed higher biomass but were seasonally more variable, as opposed to Q. ilex forests where the mycelial biomass remained lower and stable over the season. Production and turnover, respectively, varied between 1.4-5.9 kg ha-1  d-1 and 7.2-9.9 times yr-1 over the different forest types and were positively correlated with 2-month and 3-month SPI over the study period. Our results demonstrated that mycorrhizal mycelial biomass varied with season and tree species and we speculate that production and turnover are related to physiology and plant host performance during drought.

Insect defoliation is linked to a decrease in soil ectomycorrhizal biomass and shifts in needle endophytic communities.

Insect outbreaks of increasing frequency and severity in forests are predicted due to climate change. Insect herbivory is known to promote physiological changes in forest trees. However, little is known about whether these plant phenotypic adjustments have cascading effects on tree microbial symbionts such as fungi in roots and foliage. We studied the impact of defoliation by the pine processionary moth in two infested Pinus nigra forests through a multilevel sampling of defoliated and non-defoliated trees. We measured tree growth, nutritional status and carbon allocation to chemical defenses. Simultaneously, we analysed the putative impact of defoliation on the needle endophytes and on the soil fungal communities. Higher concentrations of chemical defenses were found in defoliated trees, likely as a response to defoliation; however, no differences in non-structural carbohydrate reserves were found. In parallel to the reductions in tree growth and changes in chemical defenses, we observed shifts in the composition of needle endophytic and soil fungal communities in defoliated trees. Defoliated trees consistently corresponded with a lower biomass of ectomycorrhizal fungi in both sites, and a higher alpha diversity and greater relative abundance of belowground saprotrophs and pathogens. However, ectomycorrhizal alpha diversity was similar between non-defoliated and defoliated trees. Specific needle endophytes in old needles were strongly associated with non-defoliated trees. The potential role of these endophytic fungi in pine resistance should be further investigated. Our study suggests that lower biomass of ectomycorrhizal fungi in defoliated trees might slow down tree recovery since fungal shifts might affect tree-mycorrhizal feedbacks and can potentially influence carbon and nitrogen cycling in forest soils.

A compendium of mutational cancer driver genes.

A fundamental goal in cancer research is to understand the mechanisms of cell transformation. This is key to developing more efficient cancer detection methods and therapeutic approaches. One milestone towards this objective is the identification of all the genes with mutations capable of driving tumours. Since the 1970s, the list of cancer genes has been growing steadily. Because cancer driver genes are under positive selection in tumorigenesis, their observed patterns of somatic mutations across tumours in a cohort deviate from those expected from neutral mutagenesis. These deviations, which constitute signals of positive selection, may be detected by carefully designed bioinformatics methods, which have become the state of the art in the identification of driver genes. A systematic approach combining several of these signals could lead to a compendium of mutational cancer genes. In this Review, we present the Integrative OncoGenomics (IntOGen) pipeline, an implementation of such an approach to obtain the compendium of mutational cancer drivers. Its application to somatic mutations of more than 28,000 tumours of 66 cancer types reveals 568 cancer genes and points towards their mechanisms of tumorigenesis. The application of this approach to the ever-growing datasets of somatic tumour mutations will support the continuous refinement of our knowledge of the genetic basis of cancer.

BnpC: Bayesian non-parametric clustering of single-cell mutation profiles.

MOTIVATION: The high resolution of single-cell DNA sequencing (scDNA-seq) offers great potential to resolve intratumor heterogeneity (ITH) by distinguishing clonal populations based on their mutation profiles. However, the increasing size of scDNA-seq datasets and technical limitations, such as high error rates and a large proportion of missing values, complicate this task and limit the applicability of existing methods. RESULTS: Here, we introduce BnpC, a novel non-parametric method to cluster individual cells into clones and infer their genotypes based on their noisy mutation profiles. We benchmarked our method comprehensively against state-of-the-art methods on simulated data using various data sizes, and applied it to three cancer scDNA-seq datasets. On simulated data, BnpC compared favorably against current methods in terms of accuracy, runtime and scalability. Its inferred genotypes were the most accurate, especially on highly heterogeneous data, and it was the only method able to run and produce results on datasets with 5000 cells. On tumor scDNA-seq data, BnpC was able to identify clonal populations missed by the original cluster analysis but supported by Supplementary Experimental Data. With ever growing scDNA-seq datasets, scalable and accurate methods such as BnpC will become increasingly relevant, not only to resolve ITH but also as a preprocessing step to reduce data size. AVAILABILITY AND IMPLEMENTATION: BnpC is freely available under MIT license at https://github.com/cbg-ethz/BnpC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Vitamin D: Between the Brightness of the sun and the Darkness of Depression. / Vitamina D: entre el brillo del sol y la oscuridad de la depresión.

INTRODUCTION: The scientific literature suggests a relationship between vitamin D (VitD) and the onset, treatment and prognosis of depression. However, this line of research continues to be controversial. The aim of the study was to analyse the relationship between depression and VitD values, controlling for the influence of the season. MATERIAL AND METHODS: Observational and cross-sectional study. The sample was made up of 150 adult female volunteer participants (aged between 28 and 78 years). The sample was stratified into three groups: a) depression without treatment, b) depression under treatment with antidepressants, and c) without depression (control). VitD values (ng/ml) were compared. RESULTS: Significant differences were found between the three groups surveyed. The group of participants with depression without treatment obtained the lowest VitD values (mean 18.62 ng/ml; SD 8.42), compatible with severe insufficiency. The group of participants with depression in treatment obtained higher values than the previous group, although in an insufficient range (mean 23.80 ng/ml; SD 11.30). The third group (control) obtained the highest values and in accordance with the desirable range (mean 30.19 ng/ml; SD 10.21). There were no age differences between the groups. When controlling for possible effects of the season, the previous differences in VitD between the three groups were maintained, with an evident decrease of all the mean levels in the winter period. CONCLUSIONS: Depression is associated with insufficient VitD values. Treatment with antidepressants improves these values, although they continue to be insufficient. The findings of this study reinforce the evidence for an association between depression and VitD.