The effect of dietary resistant starch type 2 on the microbiota and markers of gut inflammation in rural Malawi children

BACKGROUND: Resistant starch (RS) decreases intestinal inflammation in some settings. We tested the hypothesis that gut inflammation will be reduced with dietary supplementation with RS in rural Malawian children. Eighteen stunted 3–5-year-old children were supplemented with 8.5 g/day of RS type 2 for 4 weeks. The fecal samples were analyzed for the microbiota, the microbiome, short chain fatty acids, metabolome, and proteins indicative of inflammation before and after the intervention. Subjects served as their own controls. RESULTS: The consumption of RS changed the composition of the microbiota; at the phylum level Actinobacteria increased, while Firmicutes decreased. Among the most prevalent genera, Lactobacillus was increased and Roseburia, Blautia, and Lachnospiracea incertae sedis were decreased. The Shannon H index at the genus level decreased from 2.02 on the habitual diet and 1.76 after the introduction of RS (P < 0.01). Fecal acetate concentration decreased, and fecal propionate concentration increased after RS administration (−5.2 and 2.0 μmol/g, respectively). Fecal calprotectin increased from 29 ± 69 to 89 ± 49 μg/g (P = 0.003) after RS was given. The lipopolysaccharide biosynthesis pathway was upregulated. CONCLUSIONS: Our findings do not support the hypothesis that RS reduces gut inflammation in rural Malawian children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-015-0102-9) contains supplementary material, which is available to authorized users

Coactivator condensation at super-enhancers links phase separation and gene control

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in the control of key cell-identity genes.National Institutes of Health (U.S.) (Grant GM123511)National Institutes of Health (U.S.) (Grant P01-CA042063)National Science Foundation (U.S.) (Grant PHY-1743900)National Cancer Institute (U.S.) (Grant P30-CA14051

Pol II phosphorylation regulates a switch between transcriptional and splicing condensates

The synthesis of pre-mRNA by RNA polymerase II (Pol II) involves the formation of a transcription initiation complex, and a transition to an elongation complex. The large subunit of Pol II contains an intrinsically disordered C-terminal domain that is phosphorylated by cyclin-dependent kinases during the transition from initiation to elongation, thus influencing the interaction of the C-terminal domain with different components of the initiation or the RNA-splicing apparatus. Recent observations suggest that this model provides only a partial picture of the effects of phosphorylation of the C-terminal domain. Both the transcription-initiation machinery and the splicing machinery can form phase-separated condensates that contain large numbers of component molecules: hundreds of molecules of Pol II and mediator are concentrated in condensates at super-enhancers, and large numbers of splicing factors are concentrated in nuclear speckles, some of which occur at highly active transcription sites. Here we investigate whether the phosphorylation of the Pol II C-terminal domain regulates the incorporation of Pol II into phase-separated condensates that are associated with transcription initiation and splicing. We find that the hypophosphorylated C-terminal domain of Pol II is incorporated into mediator condensates and that phosphorylation by regulatory cyclin-dependent kinases reduces this incorporation. We also find that the hyperphosphorylated C-terminal domain is preferentially incorporated into condensates that are formed by splicing factors. These results suggest that phosphorylation of the Pol II C-terminal domain drives an exchange from condensates that are involved in transcription initiation to those that are involved in RNA processing, and implicates phosphorylation as a mechanism that regulates condensate preference

Adiabatic perturbation theory and geometry of periodically-driven systems

We give a systematic review of the adiabatic theorem and the leading non-adiabatic corrections in periodically-driven (Floquet) systems. These corrections have a two-fold origin: (i) conventional ones originating from the gradually changing Floquet Hamiltonian and (ii) corrections originating from changing the micro-motion operator. These corrections conspire to give a Hall-type linear response for non-stroboscopic (time-averaged) observables allowing one to measure the Berry curvature and the Chern number related to the Floquet Hamiltonian, thus extending these concepts to periodically-driven many-body systems. The non-zero Floquet Chern number allows one to realize a Thouless energy pump, where one can adiabatically add energy to the system in discrete units of the driving frequency. We discuss the validity of Floquet Adiabatic Perturbation Theory (FAPT) using five different models covering linear and non-linear few and many-particle systems. We argue that in interacting systems, even in the stable high-frequency regimes, FAPT breaks down at ultra slow ramp rates due to avoided crossings of photon resonances, not captured by the inverse-frequency expansion, leading to a counter-intuitive stronger heating at slower ramp rates. Nevertheless, large windows in the ramp rate are shown to exist for which the physics of interacting driven systems is well captured by FAPT.The authors would like to thank M. Aidelsburger, M. Atala, E. Dalla Torre, N. Goldman, M. Heyl, D. Huse, G. Jotzu, C. Kennedy, M. Lohse, T. Mori, L. Pollet, M. Rudner, A. Russomanno, and C. Schweizer for fruitful discussions. This work was supported by AFOSR FA9550-16-1-0334, NSF DMR-1506340, ARO W911NF1410540, and the Hungarian research grant OTKA Nos. K101244, K105149. M. K. was supported by Laboratory Directed Research and Development (LDRD) funding from Berkeley Lab, provided by the Director, Office of Science, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The authors are pleased to acknowledge that the computational work reported in this paper was performed on the Shared Computing Cluster which is administered by Boston University's Research Computing Services. The authors also acknowledge the Research Computing Services group for providing consulting support which has contributed to the results reported within this paper. The study of the driven non-integrable transverse-field Ising model was carried out using QuSpin [185] - an open-source state-of-the-art Python package for dynamics and exact diagonalization of quantum many body systems, available to download here. (FA9550-16-1-0334 - AFOSR; DMR-1506340 - NSF; W911NF1410540 - ARO; K101244 - Hungarian research grant OTKA; K105149 - Hungarian research grant OTKA; DE-AC02-05CH11231 - Laboratory Directed Research and Development (LDRD) funding from Berkeley Lab)https://arxiv.org/pdf/1606.02229.pd

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Coactivator condensation at super-enhancers links phase separation and gene control

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in the control of key cell-identity genes

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting