Emergent simplicity in microbial community assembly

Published in final edited form as: Science. 2018 August 03; 361(6401): 469–474. doi:10.1126/science.aat1168.A major unresolved question in microbiome research is whether the complex taxonomic architectures observed in surveys of natural communities can be explained and predicted by fundamental, quantitative principles. Bridging theory and experiment is hampered by the multiplicity of ecological processes that simultaneously affect community assembly in natural ecosystems. We addressed this challenge by monitoring the assembly of hundreds of soil- and plant-derived microbiomes in well-controlled minimal synthetic media. Both the community-level function and the coarse-grained taxonomy of the resulting communities are highly predictable and governed by nutrient availability, despite substantial species variability. By generalizing classical ecological models to include widespread nonspecific cross-feeding, we show that these features are all emergent properties of the assembly of large microbial communities, explaining their ubiquity in natural microbiomes.The funding for this work partly results from a Scialog Program sponsored jointly by the Research Corporation, for Science Advancement and. the Gordon and Betty Moore Foundation through grants to Yale University and Boston University by the Research Corporation and by the Simons Foundation. This work was also supported by a young; investigator award from the Human Frontier Science Program to A.S. (RGY0077/2016) and by NIH NIGMS grant 1R35GM119461 and a Simons Investigator as in the Mathematical Modeling of Living Systems (MMLS) to P.M.; D.S. and J.E.G. additionally acknowledge funding from the Defense Advanced Research Projects Agency (purchase request no. HR0011515303, contract no.. HR0011-15-0-0091), the U.S. Department of Energy (DE-SC0012627), the NIH (T32GM100842, 5R01DE024468, R01GM121950, and Sub_P30DK036836_P&F), the National Science Foundation (1457695), the Human Frontier Science Program (RGP0020/2016) and the Boston University Interdisciplinary Biomedical Research Office. (Research Corporation, for Science Advancement; Gordon and Betty Moore Foundation; Boston University by the Research Corporation; Simons Foundation.; RGY0077/2016 - uman Frontier Science Program; 1R35GM119461 - NIH NIGMS grant; Simons Investigator as in the Mathematical Modeling of Living Systems (MMLS); HR0011515303 - Defense Advanced Research Projects Agency; HR0011-15-0-0091 - Defense Advanced Research Projects Agency; T32GM100842 - NIH; 5R01DE024468 - NIH; R01GM121950 - NIH; ub_P30DK036836 - NIH; 1457695 - National Science Foundation; RGP0020/2016 - Human Frontier Science Program; Boston University Interdisciplinary Biomedical Research Office)Accepted manuscrip

Effect of resistance training and hypocaloric diets with different protein content on body composition and lipid profile in hypercholesterolemic obese women

Lifestyle changes such as following a hypocaloric diet and regular physical exercise are recognized as effective non-pharmacological interventions to reduce body fat mass and prevent cardiovascular disease risk factors. Purpose: To evaluate the interactions of a higher protein (HP) vs. a lower protein (LP) diet with or without a concomitant progressive resistance training program (RT) on body composition and lipoprotein profile in hypercholesterolemic obese women. Methods: Retrospective study derived from a 16-week randomized controlled-intervention clinical trial. Twentyfive sedentary, obese (BMI: 30-40 kg/m²) women, aged 40-60 with hypercholesterolemia were assigned to a 4-arm trial using a 2 x 2 factorial design (Diet x Exercise). Prescribed diets had the same calorie restriction (-500 kcal/day), and were categorized according to protein content as: lower protein ( 22% daily energy intake, HP). Exercise comparisons involved habitual activity (control) vs. a 16-week supervised whole-body resistance training program (RT), two sessions/wk. Results: A significant decrease in weight and waist circumference was observed in all groups. A significant decrease in LDL-C and Total-Cholesterol levels was observed only when a LP diet was combined with a RT program, the RT being the most determining factor. Interestingly, an interaction between diet and exercise was found concerning LDL-C values. Conclusion: In this study, resistance training plays a key role in improving LDL-C and Total-Cholesterol; however, a lower protein intake (< 22% of daily energy intake as proteins) was found to achieve a significantly greater reduction in LDL-C

Changes in anthropometry and performance, and their inter-relationships, across three seasons in elite youth rugby league players

This is a non-final version of an article published in final form in Journal of Strength and Conditioning Research, 2014, 28(11), pp. 3128-3136.This study investigated changes in anthropometry and performance, and their inter-relationships, across three consecutive seasons (under-15 to under-17 age group) in elite youth rugby league players. Each player took part in annual anthropometrical and performance assessments, comprising measurements of stature; body mass; limb lengths and circumference; skinfolds, predicted muscle cross-sectional area (CSA); 20 m speed, counter-movement jump height, vertical power and aerobic power. Lean body mass % changed (P < 0.05) between the under-15 (70.9 ± 5.9 %), under-16 (72.0 ± 5.8 %) and the under-17 age groups (74.1 ± 5.7 %). Likewise, predicted quadriceps muscle cross-sectional area (CSA) also changed (P < 0.05) between each age group (under-15 = 120.9 ± 37.8 cm2; under-16 = 133.2 ± 36.0 cm2; under-17 = 154.8 ± 28.3 cm2). Concomitant changes between the under-15 and under-16 group were found for 20 m speed (3.5 ± 0.1 cf. 3.4 ± 0.2 s; P = 0.008) and predicted jumping power (3611.3 ± 327.3 W cf. 4081.5 ± 453.9 W; P = 0.003). Both lean body mass and quadriceps muscle CSA consistently, related to both 20 m sprint time and jumping power, with r-values ranging between -0.39 to –0.63 (20 m sprint time) and 0.55 to 0.75 (jumping power). Our findings demonstrate the importance of gains in lean body mass across later-adolescence that support the ability to generate horizontal speed and predicted vertical power. This information should inform the expectations and subsequent training programs of elite rugby league practitioners

Anaerobic Energy Expenditure and Mechanical Efficiency during Exhaustive Leg Press Exercise

Information about anaerobic energy production and mechanical efficiency that occurs over time during short-lasting maximal exercise is scarce and controversial. Bilateral leg press is an interesting muscle contraction model to estimate anaerobic energy production and mechanical efficiency during maximal exercise because it largely differs from the models used until now. This study examined the changes in muscle metabolite concentration and power output production during the first and the second half of a set of 10 repetitions to failure (10RM) of bilateral leg press exercise. On two separate days, muscle biopsies were obtained from vastus lateralis prior and immediately after a set of 5 or a set of 10 repetitions. During the second set of 5 repetitions, mean power production decreased by 19% and the average ATP utilisation accounted for by phosphagen decreased from 54% to 19%, whereas ATP utilisation from anaerobic glycolysis increased from 46 to 81%. Changes in contraction time and power output were correlated to the changes in muscle Phosphocreatine (PCr; r = −0.76; P<0.01) and lactate (r = −0.91; P<0.01), respectively, and were accompanied by parallel decreases (P<0.01-0.05) in muscle energy charge (0.6%), muscle ATP/ADP (8%) and ATP/AMP (19%) ratios, as well as by increases in ADP content (7%). The estimated average rate of ATP utilisation from anaerobic sources during the final 5 repetitions fell to 83% whereas total anaerobic ATP production increased by 9% due to a 30% longer average duration of exercise (18.4±4.0 vs 14.2±2.1 s). These data indicate that during a set of 10RM of bilateral leg press exercise there is a decrease in power output which is associated with a decrease in the contribution of PCr and/or an increase in muscle lactate. The higher energy cost per repetition during the second 5 repetitions is suggestive of decreased mechanical efficiency

Rad3ATR Decorates Critical Chromosomal Domains with γH2A to Protect Genome Integrity during S-Phase in Fission Yeast

Schizosaccharomyces pombe Rad3 checkpoint kinase and its human ortholog ATR are essential for maintaining genome integrity in cells treated with genotoxins that damage DNA or arrest replication forks. Rad3 and ATR also function during unperturbed growth, although the events triggering their activation and their critical functions are largely unknown. Here, we use ChIP-on-chip analysis to map genomic loci decorated by phosphorylated histone H2A (γH2A), a Rad3 substrate that establishes a chromatin-based recruitment platform for Crb2 and Brc1 DNA repair/checkpoint proteins. Unexpectedly, γH2A marks a diverse array of genomic features during S-phase, including natural replication fork barriers and a fork breakage site, retrotransposons, heterochromatin in the centromeres and telomeres, and ribosomal RNA (rDNA) repeats. γH2A formation at the centromeres and telomeres is associated with heterochromatin establishment by Clr4 histone methyltransferase. We show that γH2A domains recruit Brc1, a factor involved in repair of damaged replication forks. Brc1 C-terminal BRCT domain binding to γH2A is crucial in the absence of Rqh1Sgs1, a RecQ DNA helicase required for rDNA maintenance whose human homologs are mutated in patients with Werner, Bloom, and Rothmund–Thomson syndromes that are characterized by cancer-predisposition or accelerated aging. We conclude that Rad3 phosphorylates histone H2A to mobilize Brc1 to critical genomic domains during S-phase, and this pathway functions in parallel with Rqh1 DNA helicase in maintaining genome integrity

Anthropometric and physical performance characteristics of top-elite, elite and non-elite youth female team handball players

This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Sports Sciences on 16/02/2015, available online: http://www.tandfonline.com/doi/pdf/10.1080/02640414.2015.1012099In order to maximise the potential for success, developing nations need to produce superior systems to identify and develop talent, which requires comprehensive and up-to-date values on elite players. This study examined the anthropometric and physical characteristics of youth female team handball players (16.07 ± 1.30 y) in non-elite (n= 47), elite (n= 37) and top-elite players (n= 29). Anthropometric profiling included sum of eight skinfolds, body mass, stature, girths, breadths and somatotype. Performance tests included 20 m sprint, counter movement jump, throwing velocity, repeated shuttle sprint and jump ability test, and Yo-Yo Intermittent Recovery Test Level 1. Youth top-elite players had greater body mass, lean mass, stature, limb girths and breadths than elite and non-elite players, while only stature and flexed arm were higher in elite compared to non-elite players (all P 0.05). Top-elite performed better in most performance tests compared to both elite and non-elite players (P 0.05). Elite outperformed non-elite players in throwing velocity only. Findings reveal that non-elite players compare unfavourably to top-elite international European players in many anthropometric and performance characteristics, and differ in few characteristics compared to elite European club team players. This study is useful for emerging team handball nations in improving talent identification processes

A Putative Transcription Factor MYT2 Regulates Perithecium Size in the Ascomycete Gibberella zeae

The homothallic ascomycete fungus Gibberella zeae is a plant pathogen that is found worldwide, causing Fusarium head blight (FHB) in cereal crops and ear rot of maize. Ascospores formed in fruiting bodies (i.e., perithecia) are hypothesized to be the primary inocula for FHB disease. Perithecium development is a complex cellular differentiation process controlled by many developmentally regulated genes. In this study, we selected a previously reported putative transcription factor containing the Myb DNA-binding domain MYT2 for an in-depth study on sexual development. The deletion of MYT2 resulted in a larger perithecium, while its overexpression resulted in a smaller perithecium when compared to the wild-type strain. These data suggest that MYT2 regulates perithecium size differentiation. MYT2 overexpression affected pleiotropic phenotypes including vegetative growth, conidia production, virulence, and mycotoxin production. Nuclear localization of the MYT2 protein supports its role as a transcriptional regulator. Transcriptional analyses of trichothecene synthetic genes suggest that MYT2 additionally functions as a suppressor for trichothecene production. This is the first study characterizing a transcription factor required for perithecium size differentiation in G. zeae, and it provides a novel angle for understanding sexual development in filamentous fungi

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson\u27s disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. METHODS AND FINDINGS: Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. CONCLUSIONS: Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death

Immunodiagnosis of endemic mycoses and bronchopulmonary aspergilosis: A multicenter study in Argentina

Fil: Canteros, C. E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Rivas, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Soria, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Lee, W. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Perrotta, Diego. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Rodero, L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Davel, Graciela Odelsia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Berducci, O. Grupo EMMB; Argentina.Fil: Bonardello, N. Grupo EMMB; Argentina.Fil: Castro, H. Grupo EMMB; Argentina.Fil: Chacón, Y. Grupo EMMB; Argentina.Fil: Cendán Colombo, L. Grupo EMMB; Argentina.Fil: De Vechi, M. Grupo EMMB; Argentina.Fil: Errecalde, G. Grupo EMMB; Argentina.Fil: Fernández, N. Grupo EMMB; Argentina.FIl: Gorostiaga, J. L. Grupo EMMB; Argentina.Fil: López, C. Grupo EMMB; Argentina.Fil: Mackay, P. Grupo EMMB; Argentina.Fil: Gonzalez, R. Grupo EMMB; Argentina.Fil: Cacace, María Luisa. Grupo EMMB; Argentina.Fil: Mestron, S. Grupo EMMB; Argentina.Fil: Mónaco, L. Grupo EMMB; Argentina.Fil: Nardin, M. E. Grupo EMMB; Argentina.Fil: Ramos, L. Grupo EMMB; Argentina.Fil: Pagella, H. Grupo EMMB; Argentina.Fil: Petrussi, N. Grupo EMMB; Argentina.Fil: Pizarro, M. R. Grupo EMMB; Argentina.Fil: Sánchez, R. Grupo EMMB; Argentina.Fil: Saporiti, A. M. Grupo EMMB; Argentina.Fil: Tichellio, A. G. Grupo EMMB; Argentina.Fil: Tiraboschi, N. Grupo EMMB; Argentina.Fil: Tonelli, L. Grupo EMMB; Argentina.Fil: Zanuso, A. Grupo EMMB; Argentina.Se realizó entre 01-04-2000 y 30-03-2001, un estudio de corte transversal, para conocer la frecuencia relativa de las enfermedades por hongos dimorfos y Aspergillus spp. en la República Argentina y evaluar la certeza en el diagnóstico de los laboratorios de diferentes áreas geográficas. Participaron 25 centros de salud provenientes de 12 provincias y de la Ciudad Autónoma de Buenos Aires. Fueron analizados en el laboratorio de origen 965 sueros de pacientes con sospecha clínica de histoplasmosis (HP), paracoccidioidomicosis (PCM), coccidioidomicosis (CM) y aspergilosis. Todos los sueros positivos y el 35% de los negativos fueron reevaluados en el laboratorio de referencia por inmunodifusión doble en agar. La concordancia entre los resultados obtenidos en los centros de origen y el de referencia fue de 98,8%. Se detectaron anticuerpos específicos en 120 sueros correspondientes a 98 pacientes. El 71,4% (70 casos) de los diagnósticos correspondió a micosis endémicas (HP, PCM y CM) y el resto a aspergilosis. PCM fue diagnosticada en 47,9% (47 casos), aspergilosis en 28,6% (28 casos), HP en13,3% (13 casos) y CM en 10,2% (10 casos). La participación en este estudio fue voluntaria y no todos los centros del país estaban representados, sin embargo, las frecuencias de enfermedades fúngicas fueron las esperadas y coincidentes con estudios previos realizados a nivel nacional. (EN) In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01- 2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM) or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done locally. All positive and 35% of negative sera were retested in the reference center. Results of laboratories of origin showed 98.8% concordance with those of reference center. Antibodies against any of the etiological agents were detected in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies of the different mycoses in decreasing order w ere PCM 47 patients (47.9%), aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients (10.2%). The study was carried out on a voluntary basis and some areas of the country were not represented. However, the frequencies were in range with the expected rates in the population under study