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Using predictions based on environmental regularities is fundamental for adaptive behavior. While it is widely accepted that predictions across different stimulus attributes (e.g., time and content) facilitate sensory processing, it is unknown whether predictions across these attributes rely on the same neural mechanism. Here, to elucidate the neural mechanisms of predictions, we combine invasive electrophysiological recordings (human electrocorticography in 4 females and 2 males) with computational modeling while manipulating predictions about content ("what") and time ("when"). We found that "when" predictions increased evoked activity over motor and prefrontal regions both at early (similar to 180 ms) and late (430 - 450 ms) latencies. "What" predictability, however, increased evoked activity only over prefrontal areas late in time (420 - 460 ms). Beyond these dissociable influences, we found that "what" and "when" predictability interactively modulated the amplitude of early (165 ms) evoked responses in the superior temporal gyrus. We modeled the observed neural responses using biophysically realistic neural mass models, to better understand whether "what" and "when" predictions tap into similar or different neurophysiological mechanisms. Our modeling results suggest that "what" and "when" predictability rely on complementary neural processes: "what" predictions increased short-term plasticity in auditory areas, whereas "when" predictability increased synaptic gain in motor areas. Thus, content and temporal predictions engage complementary neural mechanisms in different regions, suggesting domain-specific prediction signaling along the cortical hierarchy. Encoding predictions through different mechanisms may endow the brain with the flexibility to efficiently signal different sources of predictions, weight them by their reliability, and allow for their encoding without mutual interference.

Ecosystems persist over geological timescales by continuously cycling nutrients. However, we lack a quantitative model of how diverse organisms organize with respect to one another. We observe these dynamics in a quasi-two-dimensional microbial ecosystem, in which all microbes live within the penetration depths of oxygen and light. This community is composed of both photosynthetic bacteria, which produce sugars and oxygen, and aerobic bacteria, which consume oxygen and sugars. Shinning a light on the community drives a nutrient cycle between these two groups of microbes. Illuminating a spot, we measure the resulting distribution of oxygen. Under normal conditions, diffusion alone stabilizes oxygen gradients. However, at freezing temperatures or low atmospheric oxygen concentration, the kinetics of microbial oxygen production and consumption dominate. Surprisingly, after three weeks, the initially uniform distribution of oxygen in the spot becomes an annulus. We present a robust method to invert the measured oxygen concentration for the distribution of oxygen sources and sinks.

Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryoelectron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context.

Measurements of azimuthal angle and transverse momentum (p(T)) correlations of isolated photons and associated jets are reported for pp and PbPb collisions at root s(NN) = 5.02 TeV. The data were recorded with the CMS detector at the CERN LHC. For events containing a leading isolated photon with p(T)(gamma) > 40 GeV/c and an associated jet with p(T)(jet) > 30 GeV/c, the photon+jet azimuthal correlation and p(T) imbalance in PbPb collisions are studied as functions of collision centrality and p(T)(gamma). The results are compared to pp reference data collected at the same collision energy and to predictions from several theoretical models for parton energy loss. No evidence of broadening of the photon+jet azimuthal correlations is observed, while the ratio p(T)(jet)/p(T)(gamma) decreases significantly for PbPb data relative to the pp reference. All models considered agree within uncertainties with the data. The number of associated jets per photon with p(T)(gamma) > 80GeV/c is observed to be shifted towards lower p(T)(jet) in central PbPb collisions compared to pp collisions. (C) 2018 The Author. Published by Elsevier B.V.

Measurements of azimuthal angular correlations are presented for high-multiplicity pPb collisions at root s(NN) = 5.02 TeV and peripheral PbPb collisions at root s(NN) = 2.76 TeV. The data used in this work were collected with the Compact Muon Solenoid (CMS) detector at the European Organization for Nuclear Research (CERN) Large Hadron Collider (LHC). Fourier coefficients as functions of transverse momentum and pseudorapidity are studied using the scalar product method; four-, six-, and eight-particle cumulants; and the Lee-Yang zero technique. The influence of event plane decorrelation is evaluated using the scalar product method and found to account for most of the observed pseudorapidity dependence.

A measurement is presented of the associated production of a single top quark and a W boson in proton -proton collisions at root s = 13 TeV by the CMS Collaboration at the CERN LHC. The data collected corresponds to an integrated luminosity of 35.9 fb(-1). The measurement is performed using events with one electron and one muon in the final state along with at least one jet originated from a bottom quark. A multivariate discriminant, exploiting the kinematic properties of the events, is used to separate the signal from the dominant tt background. The measured cross section of 63.1 +/- 1.8(stat) +/- 6.4(syst) +/- 2.1 (lumi) pb is in agreement with the standard model expectation.

An effective tumoral delivery system should show minimal removal by the reticuloendothelial system (RES), promote tumor uptake and penetration, and minimize on-site clearance. This study reports the design and synthesis of advanced self-assembling peptide nanofiber precursor (NFP) analogues. The peptidic nature of NFP offers the design flexibility for on-demand customization with imaging agents and surface charges while maintaining a set size, allowing for real-time monitoring of kinetic and dynamic tumoral delivery by multimodal fluorescence/positron emission tomography/computed tomography (fluo/PET/CT) imaging, for formulation optimization. The optimized glutathione (GSH)-NFP displays a reduced capture by the RES as well as excellent tumor targeting and tissue invasion properties compared to naive NFP. Inside a tumor, GSH-NFP can structurally transform into ten times larger interfibril networks, serving as in situ depot that promotes weeks-long local retention. This nanofiber, which can further be designed to release the active pharmacophores within a tumor microenvironment, displays a superior therapeutic efficacy for inhibiting disease progression and improving the survival of animals bearing triple-negative breast cancer tumors compared to free drug and liposome formulation of the drug, in addition to a favorable toxicity profile.

The epithelial barrier of the gastrointestinal tract is home to numerous intraepithelial T cells (IETs). IETs are functionally adapted to the mucosal environment and are among the first adaptive immune cells to encounter microbial and dietary antigens. They possess hallmark features of tissue-resident T cells: they are long-lived nonmigratory cells capable of rapidly responding to antigen challenges independent of T cell recruitment from the periphery. Gut-resident T cells have been implicated in the relapsing and remitting course and persisting low-grade inflammation of chronic gastrointestinal diseases, including IBD and coeliac disease. So far, most data IETs have been derived from experimental animal models; however, IETs and the environmental makeup differ between mice and humans. With advances in techniques, the number of human studies has grown exponentially in the past 5 years. Here, we review the literature on the involvement of human IETs in gut homeostasis and inflammation, and how these cells are influenced by the microbiota and dietary antigens. Finally, targeting of IETs in therapeutic interventions is discussed. Broad insight into the function and role of human IETs in gut homeostasis and inflammation is essential to identify future diagnostic, prognostic and therapeutic strategies.

The polymerase-associated factor 1 (Paf1) complex is a general transcription elongation factor of RNA polymerase II, which is composed of five core subunits, Paf1, Ctr9, Cdc73, Leo1, and Rtf1, and functions as a diverse platform that broadly affects gene expression genome-wide. In this study, we solved the 2.9-A crystal structure of the core region composed of the Ctr9-Paf1-Cdc73 ternary complex from a thermophilic fungi, which provides a structural perspective of the molecular details of the organization and interactions involving the Paf1 subunits in the core complex. We find that Ctr9 is composed of 21 tetratricopeptide repeat (TPR) motifs that wrap three circular turns in a right-handed superhelical manner around the N-terminal region of an elongated singlepolypeptide-chain scaffold of Paf1. The Cdc73 fragment is positioned within the surface groove of Ctr9, where it contacts mainly with Ctr9 and minimally with Paf1. We also identified that the Paf1 complex preferentially binds single-strand-containing DNAs. Our work provides structural insights into the overall architecture of the Paf1 complex and paves the road forward for understanding the molecular mechanisms of the Paf1 complex in transcriptional regulation.